REVIEW OPEN ACCESS
Consensus-based care recommendations forcongenital and childhood-onset myotonicdystrophy type 1Nicholas E Johnson MD MSCI Eugenio Zapata Aldana MD Nathalie Angeard PhD Tetsuo Ashizawa MD
Kiera N Berggren MACCC-SLP MS Chiara Marini-Bettolo MD PhD Tina Duong MPT PhD
Anne-Berit Ekstrom MD PhD Valeria Sansone MD Cuixia Tian MD Leah Hellerstein LCSW MPH
and Craig Campbell MD on behalf of the Myotonic Dystrophy Foundation
Neurology Clinical Practice October 2019 vol 9 no 5 443-454 doi101212CPJ0000000000000646
Correspondence
Leah Hellerstein LCSW MPH
LeahHellersteinmyotonicorg
AbstractPurpose of reviewMyotonic dystrophy type 1 is a multisystemic disorder caused bya noncoding triplet repeat The age of onset is variable across thelifespan but in its most severe form the symptoms appear at birth(congenital myotonic dystrophy) or in the pediatric age range(childhood-onset myotonic dystrophy) These children havea range of disabilities that reduce the lifespan and cause significantmorbidity Currently there are no agreed upon recommendationsfor caring for these children
Recent findingsTheMyotonic Dystrophy Foundation recruited 11 international clinicians who are experiencedwith congenital and childhood-onset myotonic dystrophy to create consensus-based carerecommendations The experts used a 2-step methodology using elements of the single textprocedure and nominal group technique Completion of this process has led to the de-velopment of clinical care recommendations for this population
SummaryChildren with myotonic dystrophy often require monitoring and interventions to improve thelifespan and quality of life The resulting recommendations are intended to standardize andimprove the care of children with myotonic dystrophy
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by a toxic CTGrepeat expansion in the 39UTR of the DMPK gene1ndash3 In adults with DM1 symptoms arecharacterized by progressive distal muscle weakness myotonia early onset cataracts cardiac andgastrointestinal problems and dysfunction in the CNS45 The multiorgan involvement is oftenmore pronounced and with earlier onset in individuals with symptom onset in childhood The ageof onset of DM1 is variable and intergenerational repeat expansion (known as anticipation) mayresult in symptom onset during childhood When symptom onset occurs at birth this is known ascongenital onset myotonic dystrophy (CDM) Symptom onset after the newborn period and up to
Virginia Commonwealth University (NEJ KNB) Richmond VA University of Western Ontario (EZA CC) Ontario Canada Inserm ampUniversity of Paris Descartes (NA) France HoustonMethodist Neurological Institute (TA) TX Institute of Genetic Medicine (CM-B) Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon TyneUK Stanford University (TD) CAQueen Silvia Childrenrsquos Hospital (A-BE) Gothenburg Sweden NEMOClinic (VS) Milan Italy Cincinnati Childrenrsquos HospitalMedical Center (CT) OH andMyotonic Dystrophy Foundation (LH) San Francisco CA
Funding information and disclosures are provided at the end of the article Full disclosure form information provided by the authors is available with the full text of this article atNeurologyorgcp
The Article Processing Charge was funded by the Myotonic Dystrophy Foundation
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 40 (CC BY-NC-ND) which permits downloadingand sharing the work provided it is properly cited The work cannot be changed in any way or used commercially without permission from the journal
Copyright copy 2019 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology 443
18 years of age is typically referred to as childhood-onset myo-tonic dystrophy (ChDM) However alternate definitions des-ignate further cut points depending on age of onset67 Althoughthe exact global prevalence is unknown children with CDMlikely represent 10ndash30 of the overall DM1 population48
These disorders cause significant morbidity and mortalityChildren with CDM often require intensive intervention atbirth because of hypotonia respiratory failure and feedingdifficulties49 For children with CDM ventilated longer than3 months there is a 30 mortality in the first year of life10
Both children with CDM and ChDM may have symptomsassociated with attention deficit hyperactivity disorder or autismspectrum disorder (sometimes referred to as social communi-cation disorder) during childhood1112 They also have signifi-cant motor delays13 and may have intractable irritable bowelsymptoms including incontinence Previous research suggeststhat 88 of individuals with congenital or childhood-onsetmyotonic dystrophy are unemployed over the age of 18 years14
Themultisystemicnaturemorbidity andmortality associatedwithcongenital and childhood-onset myotonic dystrophy necessitatethe development of care recommendations to standardize careThese consensus-based recommendations will also set the foun-dation for innovative clinical initiatives where gaps exist and alsofurther research to improve aspects of management These carerecommendations may also better prepare the pediatric DM1community for future clinical trials because variation in clinical caremay have significant effects on the outcome of children partici-pating in geographically dispersed clinical research sites
MethodsParticipant recruitmentThe Myotonic Dystrophy Foundation recruited cliniciansfrom the United States Canada and Europe who have ex-perience in the treatment of children with DM1 to developconsensus-based recommendations
Consensus approachAs previously described the Myotonic Dystrophy Founda-tion developed a two-phase consensus buildingmethodologyusing components of the single text procedure and nominalgroup technique15 This approach was chosen given both thesparsity of literature surrounding many of the clinical aspectsand the extensive experience of the clinicians in this area
Three of the authors (NEJ CC and EZ) created theinitial draft document drawing from the existing literatureand clinical practice that served as an initial text for the rec-ommendation developments
After creation of the single text stakeholders were engagedto refine the recommendations through a consensus-basedapproach The experts were initially assigned to specific areas ofrecommendations where they refined the recommendations Afacilitator (LH) then lead a series of meetings to review reviseand finalize the recommendations with the entire author panel
These efforts led to the final consensus-based care recom-mendations along with a quick reference guide The care rec-ommendations are divided into 2 main sections the GeneralCare Considerations and Systems-based Approach to Manage-ment Because there are differences between childhood-onsetand congenital-onset DM1 recommendations specific to CDMare separated throughout the document The Quick ReferenceGuide is provided as an appendix and the full document isavailable online (appendix e-1 linkslwwcomCPJA89) Bothfeature flowcharts and other infographics for ease of use
ResultsSee full recommendations at Neurologyorgcp
General care considerationsDiagnosis and classification
c The diagnosis of DM1 should be suspected in any childwith a family history of DM1 andor presenting withone or more of the following features Eyelid ptosis andor oral motor weakness Distal weakness primarily of the finger and wrist flexorswithout contractures or weakness of the neck flexors
Myotonia or ldquostiffnessrdquo of muscles Autistic features or social communication difficulties Attention deficit disorder anxiety and other behav-ioral problems
Developmental delay andor Intellectual disability
The age of onset of DM1 is variable
and intergenerational repeat
expansion (known as anticipation)
may result in symptom onset during
childhood
The multisystemic nature morbidity
and mortality associated with
congenital and childhood-onset
myotonic dystrophy necessitate the
development of care
recommendations to standardize and
improve the care of this population
444 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
Learning disabilities (eg dyslexia dyscalculia) Excessive daytime sleepiness (EDS) Gastrointestinal issues constipation or diarrhea Scoliosis Arrhythmia Prolonged recovery or respiratory arrest after anesthesia Neonatal features of hypotonia weakness club footrespiratory distress or feeding problems
c The classification of congenital and childhood-onsetDM1 is provided in table 1 in Quick Reference GuideNote that diagnosis may be made retrospectively afterreviewing symptom onset Fetal tissue with long CTGrepeats should not be called CDMbecause this diagnosisis reserved for newborns In these cases we wouldsuggest use of fetal DM1 as more appropriate
c Genetic counseling is recommended for patientsexhibiting clinical signs indicative of DM1 or have at-risk family members to enable them to make aninformed decision about whether to proceed to genetictesting Individuals with 37ndash49 CTG repeats aredeemed very unlikely to develop detectable DM1symptoms However such ldquopremutationsrdquo can expandinto the disease range in subsequent generationsparticularly when transmitted by women Individualsthus identified should be offered genetic counseling(see Genetic counseling) to discuss their risk fortransmitting DM1
Genetic counselingc Referral to genetic counseling (see nsgcorg) is recom-
mended for all patients with congenital and childhood-onset DM1 and their parents and to assess the parents forthe diagnosis of DM1
c Genetic counseling in affected families should conveyinformation about The inheritance pattern of disease (autosomal
dominant inheritance) The wide variability in the scope and severity of DM1
symptoms even within the same family The possibility of changes in symptom scope and
severity over time The likelihood that the mutation will expand and the
disease will become more severe as it is passed fromgeneration to generation (anticipation)
Particular attention to the possibility of a minimallyaffected mother giving birth to a severely affected child
Options for family planningc Do not use CTG repeat numbers if available for genetic
advice or prognostication these need to be discussedwith a genetic counselor Specifically repeat size may bean indicator of severity but it does not provide anyinformation about the prognosis
Focus on CDMc Once a family has had a child with CDM there is an
increased risk that the next affected child with DM1 islikely to have congenital form as well
Neonatal care A high-risk obstetrician should provide prenatal obstetric
care for mothers known or suspected to carry a child withDM1
Pediatric or neonatal specialist should be present atdelivery if a mother is known to have DM1 or if the childis known or suspected to have DM1
Focus on CDM Children with CDM will often need management in
a neonatal intensive care unit with the capability to dealwith breathing and feeding support This team requiresa range of neonatal and consulting specialists who canmanage the genetic respiratory gastrointestinal or-thopedic neuromuscular neurosurgical and cardiacissues See figure 1 in Quick Reference Guide forneonatal care
End of life counseling and management Recommend the introduction of palliative care at the
time of diagnosis and at regular intervals thereafter Whena formal pediatric palliative care team is available theyshould be consulted
Recognize and address caregiver burden whether thecaregiver has DM1 offering respite care or equivalentmeasures to patient to improve family support Addressnormal grief on the part of the patient and family andoffer counseling as appropriate
Establish an emergency health care plan and advancedirectives with the family
Focus on CDM Introduce the concept that the natural history of the
disease includes progressive improvement of strength forthe first decade of life however the complications ofCDM can be critical and have a high risk of mortalityparticularly in the first year of life
Advise families or caregivers that invasive and non-invasive ventilation (NIV) and nutrition through gastro-stomy tube are acceptable parts of care for patients withCDM
Surgery and anesthesia Inform all caregivers that anyone administering an
anesthetic should be aware of the DM1 diagnosis When possible combine procedures under a single
sedation Arrange for a preanesthetic visit for all children planning
to have deep sedation for a diagnostic test procedureor surgery If possible include a pulmonologist withexpertise in neuromuscular diseases during this visit
Even if the patient has mild DM1 monitoring for a longerperiod of time than is typical following anesthesia orsurgery will allow for identifying serious adverse events inthe hospital setting
Providers are encouraged to review the MyotonicDystrophy Foundation Practical Suggestions for the
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 445
Anesthetic Management of a Myotonic Dystrophy Patient(myotonicorgsitesdefaultfilesMDF_LongForm_AnesGuidelines_01Cpdf) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia and the Anesthesia Quick ReferenceGuide (myotonicorgsitesdefaultfilesMDF Anes-thesia Guidelines FNL 2016 2 2 pdf) These docu-ments should be reviewed before treatment decisions
Focus on CDM It is worth noting that children with CDM are at a higher
risk of anesthetic complications given the underlyingrespiratory involvement as opposed to those withchildhood-onset myotonic dystrophy
Systems-based approachto managementRespiratory Signs of respiratory problems in children with myotonic
dystrophy include ineffective cough recurrent pulmo-nary infections orthopnea dyspnea poor sleep morningheadaches apnea fatigue and snoring
See figure 2 in Quick Reference Guide for a flowchart oftesting and treatment options in congenital andchildhood-onset myotonic dystrophy
Focus on CDM For CDM children who remain on longer term trach
ventilation there is often improvement in respiratorystrength over time and consideration to decannulatea tracheostomy should be made after careful considerationwith the multidisciplinary team including neurologyrespirology ear nose and throat and the familyConsideration of airway control respiratory infectionfrequency ability to tolerate a facial or nasal mask for NIVand compliance and cooperation with maintenancepulmonary therapy such as cough assist breathe stakingetc Testing for hypoventilation in sleep should be donebefore decannulation
Cardiovascularc Inform families of the risks of arrhythmias and cardiac
dysfunction and the importance of prompt medicalattention if symptoms are observed (ie palpitationspresyncope syncope dyspnea chest pain unexplainedfatigue) A 12-lead ECG should be performed at DM1 diagnosisand if normal and the patient remains asymptomatic ECGshould be performed annually and warrants moreinvestigation if the patient is symptomatic
If the ECG is normal and clinical suspicion is high a24-hour Holter monitor may be considered asa second-line investigation
Because specific medications such as mexiletine andpsychostimulants are antiarrhythmic an ECG before
use again within 3 months of starting therapy andthen at serial intervals is recommended
Consider in-hospital cardiac monitoring to detectarrhythmias if admitted for longer duration thantypical after surgical procedures or if admitted due tosevere illness or infection
c For young DM1 patients serial exercise stress testingand signal-averaged ECGs may be considered
c Evaluate and treat using American Heart Association(AHA) Management of Cardiac Involvement AssociatedWith Neuromuscular Diseases A Scientific Statement Fromthe American Heart Association 2017 circahajournalsorgcontent13613e200long and ACC ([AmericanCollege of Cardiology]AHA)ESC (European Societyof Cardiology) Guidelines for Management of Patientswith Ventricular Arrhythmias and the Prevention of SuddenCardiac Death (see ncbinlmnihgovpubmed16949478)- section on pediatric issues 134
Skeletal muscle weakness orthopediccomplications and rehabilitation
c Children should be evaluated early and often forphysical occupational and speech therapy needs withspecific attention to Feeding concerns and dysphagia Gross motor delay Gross and fine motor weakness Dysarthria and potential augmentative and alternativecommunication needs
Language acquisition delaysc The spine should be assessed for scoliosis and if
necessary consider bracing or referral to orthopedicsurgeon
c Children should be encouraged to participate in speechtherapy targeting speech language and communicationfrom a very early age
Focus on CDM Newborns with CDM often having difficulty feeding and
alternative nutrition should be considered After abouta year of actively working with a speech therapist oroccupational therapist most children can generally starton oral feeding
Children with CDM experience progressive improve-ment in their proximal strength until adolescence ata minimum Therefore children should be encouraged toparticipate in physical activities
Prevention of joint contractures are key to managementand should be closely monitored with early initiation ofstretching Treatment of talipes equinovarus and otherjoint contractures should include initial stretchingregimen and appropriate ankle bracing (for talipesequinovarus) Serial casting may be considered
Skeletal muscle myotoniac Delayed relaxation after grip or percussion difficulty
related to activities of daily life progressive speech
446 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
impairment or profound irritable bowel symptoms aresigns often related to myotonia
c Mexiletine (Mexitil) is an option for myotonia if it isdemonstrated and is distressing to the patient Mexiletinemay not be approved for use in every country In these casesother sodium channel antagonists may be considered Because mexiletine is an antiarrhythmic an ECG
before use again within 3 months of starting therapyand then at serial intervals is recommended
Instruct the patient to avoid dyspepsia and transientldquodizzy feelingsrdquo associated with mexiletine treatmentby taking it with food to extend absorption and lowerpeak level in blood
Ocular and hearing management Baseline audiometry should be performed especially at
school age Ophthalmologic assessment should be performed at
diagnosis and at least yearly to evaluate for hyperopiastigmatism strabismus and visual acuity to preventevolution of visual impairment
Eyelid ptosis if ptosis becomes severe and interferes withvision intervention such as eyelid ldquocrutchesrdquo that can beinserted into glasses may be warranted Try crutches asa remedy for ptosis before eyelid surgery is consideredbecause of anesthesia risks Ophthalmic lubricants for dryeye may be considered
Gastrointestinal andgenitourinary management
c Presence of gastrointestinal symptoms such as abdom-inal pain constipation fecal incontinence or diarrheamay be a frequent problem The symptoms may mimicirritable bowel syndrome (IBS)15 Fiber supplementa-tion (more than 8 g daily) is the first-line treatment
c Gentle laxatives (see below) for constipation Oilsshould be avoided as they will lead to diarrhea Ifa patient does not respond to the first- or second-linerecommendations below a referral to a gastrointestinalspecialist for anal manometry should be considered First-line therapy recommendations polyethylene
glycol (Miralax) senna (Ex-Lax Senokot) docusate(Colace) or lactulose (Cholac)
Second-line therapy recommendations bisacodyl(Dulcolax Correctol) lubiprostone (Amitiza) orlinaclotide (Linzess)
Metoclopramide (Reglan) may be used to reduce thesymptoms of gastroparesis pseudo-obstruction andgastric reflux Providers should be aware of the risk ofacute dystonic reactions with this medication Long-term use is not recommended because this drug cancause tardive dyskinesia
Cholestyramine and loperamide are other options inthe presence of mainly diarrhea and anticholinergicdrug such as hyoscyamine sulfate in the presence ofIBS Because anticholinergic drugs may be antiar-rhythmic see Cardiac section on management
Mexiletine may be considered for refractory diarrheaor constipation because the drug may be antiarrhyth-mic see Cardiac section on management
c If bacterial overgrowth is found on breath testingtreating with antibiotics may reduce diarrhea
Focus on CDM As mentioned in the neonatal care section children with
CDMmay require a temporary feeding tube If dysphagiapersists consider enteral nutrition Refer to speech therapyChildren should be periodically re-assessed for improvingdysphagia
Children with CDMoften benefit from dysphagia therapyWith aggressive dysphagia therapy children with CDMoften are able to feed orally within the first year of life
Neurodevelopmental managementRecommendations
c Neuropsychological testing should be performed inevery child with DM1 to delineate cognitive strengthsand weaknesses This may include the following Psychometric assessment of global intellectual abilityand adaptive functioning
Assessment of executive functions Assessment of social cognition Assessment of visuomotor integration and visuospatialability
Assessment of receptive and expressive language abilities Assessment of EDS Assessment of learning disabilities (specific tests fordyscalculia dyslexia and dyspraxia)
c The assessments should be performed in the congenitalform in preschool age and should be repeated depend-ing on the level of functioning 2ndash3 times beforeadulthood In childhood DM1 neuropsychologicaltesting is recommended at diagnosis and repeated inpreschool or school age and college period
c Patients with psychiatric or behavioral issues should bereferred to a mental health care professional forassessment of Autism Spectrum Disorders AttentionDeficit disorders with or without Hyperactivity alex-iythmia and other behavioral problems
c Psychostimulants may be beneficial if attention deficitsare associated with an impairing level of fatigue or EDS(see excessive daytime sleepiness) As psychostimulantsmay be proarrhythmic see Cardiac section on stimulantmanagementSerotonin-enhancing antidepressants if excessive anxietyor other treatable psychiatric symptoms are present
Specific cognitive remediation programs to enhance socialemotional abilities (visual contact joint attention emotionalregulation) or executive functions efficiency (inhibitorycontrol attention working memory and cognitive flexibil-ity) using dedicated software (eg Cogmedreg)
c Language remediation and reading therapy should beconsidered because of the presence of cognitive deficitseven in children with normal intelligence Attention deficit
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 447
fatigability and visualndashspatial construction dysfunctioncan result in specific learning disorders with impair-ment in reading and spelling as well as in mathematics
Psychosocial management Healthcare professionals have a responsibility to co-
ordinate specialist care and support services for childrenwith DM1 There is a need to be alert to the psychologicaland social dysfunctions and monitor home and educa-tional circumstances Liaison between agencies is essentialto ensure a consistent approach between health educationand social care agencies
Children with DM1 should have access to appropriatepsychological and therapy services at an early age to ensurethey are fulfilling their maximum potential and learningcoping strategies for later life The modification of activitiesincluding social engagement strategies would providea foundation for each child to grow in confidence and esteem
Family care and support is essential throughout child-hood with support and social care assistance whererequired Schools should be provided with specialistinformation about the care and management of a childwith DM1 A social work consult or a referral to nursingcase management can also be beneficial for patients Aholistic approach is critical because the affected parentmay also need additional assistance
Families should have access to disability benefitsadequate housing and adaptations during the progressionof the condition
Excessive daytime sleepiness Family members and educators should be educated about
the EDS that comes with DM1 Children should be screened for signs of EDS including
prolonged naps or falling asleep in school Possible sleep apnea should be evaluated with overnight
oximetry or polysomnogram Positive-pressure ventilation can be considered if a DM1
patientrsquos sleepiness is thought to be related to nocturnalor daytime hypoventilation or sleep apnea Patientsshould be referred to pulmonologists who have experi-ence in neuromuscular diseases for consideration ofassisted ventilation
Stimulant therapy with a psychostimulant such asmodafinil (Provigil) methylphenidate or other stimulantcan be considered if central hypersomnia is suspectedOften difficulty staying awake in school is a triggeringfactor Special care should be taken in children withpreviously detected cardiac arrhythmia (See Cardiacsection on stimulant management)
Endocrine and metabolismc DM1 male patients should undergo a detailed physical
examination in search of gonadal atrophy or cryptorchidismc Patients should have a HbA1c and thyroid-stimulating
hormone and Free T4 level measured at baseline andevery 3 years or if there is a clinical suspicion
c Adolescent patients should be screened as adult patients Gonadal insufficiency and complications of the
reproductive system Inquiring about amenorrheaor dysmenorrhea for the female patients and erectiledysfunction for male patients
Fasting blood lipids plasma glucose liver enzymesbilirubin levels and gamma-glutamyl transpeptidaseshould be measured at baseline
ConclusionsThe recommendations for care of congenital and childhood-onset myotonic dystrophy have been created by consensus ofclinicians experienced in their care management Given theabsence of rigorous studies in many of these areas theseguidelines were created by consensus They are designed tostandardize the care of children with a multisystemic disorderthat leads to significant morbidity and mortality
Study fundingMyotonic Dystrophy Foundation
DisclosureN Johnson serves on the scientific advisory boards ofCytokinetics AveXis AMO Pharma and Biogen Idec hasreceived funding for travel andor speaker honoraria fromStrongbridge serves as a consultant for AMO PharmaAveXis and Vertex Pharma and receives research supportfrom Ionis Pharmaceuticals Biogen Idec Valerion Thera-peutics Cytokinetics Acceleron AveXis AMO PharmaNIHNINDS FDA Muscular Dystrophy Association andMyotonic Dystrophy Foundation EZ Aldana and NAngeard report no disclosures T Ashizawa serves on sci-entific advisory boards for the Myotonic Dystrophy Foun-dation NIH and National Ataxia Foundation has receivedfunding for travel from Biohaven PacBio and NIHreceives research support from Myotonic DystrophyFoundation National Ataxia Foundation Biohaven Phar-maceuticals Biogen andNIHNINDS and is a professor atWeill Cornell Medical College adjunct professor at BaylorCollege of Medicine guest faculty at Central South Uni-versity China KN Berggren serves on the scientific advi-sory board of Biogen and receives funding for travel andorspeaker honoraria from HDSA and FSH Society C Marini-Bettolo has served on the scientific advisory boards ofAvexis and Biogen T Duong A-B Ekstrom V Sansone CTian and L Hellerstein report no disclosures C Campbellserves on the scientific advisory boards of Catabasis andPTC Therapeutics and receives research support fromValerion Pharmaceuticals PTC Therapeutics Pfizer IonisEli Lilly Prosensa Child Health Foundation and JessersquosJourney Foundation Full disclosure form informationprovided by the authors is available with the full text of thisarticle at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 21 2018 Accepted infinal form March 4 2019
448 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
Appendix Authors
Name Location Role Contribution
Nicholas EJohnson MDMCSI
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscriptpublication of thedraft and revision
EugenioZapataAldana MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NathalieAngeard PhD
Inserm ampUniversity of ParisDescartes ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
TetsuoAshizawa MD
HoustonMethodistNeurologicalInstitute Texas
Author Data acquisitiondrafting andrevision of themanuscript
Kiera NBerggren MACCC-SLP MS
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscript
Chiara Marini-Bettolo MDPhD
Institute of GeneticMedicineNewcastleUniversity andNewcastle uponTyne HospitalsNHS FoundationTrust Newcastleupon Tyne UK
Author Data acquisitiondrafting andrevision of themanuscript
Appendix (continued)
Name Location Role Contribution
Tina DuongMPT PhD
StanfordUniversity CA
Author Data acquisitiondrafting andrevision of themanuscript
Anne-BeritEkstrom MDPhD
Queen SilviaChildrenrsquo sHospitalGothenburgSweden
Author Data acquisitiondrafting andrevision of themanuscript
ValeriaSansone MD
NEMO ClinicMilan Italy
Author Data acquisitiondrafting andrevision of themanuscript
Cuixia TianMD
CincinnatiChildrenrsquos HospitalMedical CenterCincinnati OH
Author Data acquisitiondrafting andrevision of themanuscript
LeahHellersteinLCSW MPH
MyotonicDystrophyFoundation SanFrancisco CA
CorrespondingAuthor
Obtaining fundingdrafting andreviewing themanuscript studyconcept anddesign
CraigCampbell MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
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References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
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454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
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reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
18 years of age is typically referred to as childhood-onset myo-tonic dystrophy (ChDM) However alternate definitions des-ignate further cut points depending on age of onset67 Althoughthe exact global prevalence is unknown children with CDMlikely represent 10ndash30 of the overall DM1 population48
These disorders cause significant morbidity and mortalityChildren with CDM often require intensive intervention atbirth because of hypotonia respiratory failure and feedingdifficulties49 For children with CDM ventilated longer than3 months there is a 30 mortality in the first year of life10
Both children with CDM and ChDM may have symptomsassociated with attention deficit hyperactivity disorder or autismspectrum disorder (sometimes referred to as social communi-cation disorder) during childhood1112 They also have signifi-cant motor delays13 and may have intractable irritable bowelsymptoms including incontinence Previous research suggeststhat 88 of individuals with congenital or childhood-onsetmyotonic dystrophy are unemployed over the age of 18 years14
Themultisystemicnaturemorbidity andmortality associatedwithcongenital and childhood-onset myotonic dystrophy necessitatethe development of care recommendations to standardize careThese consensus-based recommendations will also set the foun-dation for innovative clinical initiatives where gaps exist and alsofurther research to improve aspects of management These carerecommendations may also better prepare the pediatric DM1community for future clinical trials because variation in clinical caremay have significant effects on the outcome of children partici-pating in geographically dispersed clinical research sites
MethodsParticipant recruitmentThe Myotonic Dystrophy Foundation recruited cliniciansfrom the United States Canada and Europe who have ex-perience in the treatment of children with DM1 to developconsensus-based recommendations
Consensus approachAs previously described the Myotonic Dystrophy Founda-tion developed a two-phase consensus buildingmethodologyusing components of the single text procedure and nominalgroup technique15 This approach was chosen given both thesparsity of literature surrounding many of the clinical aspectsand the extensive experience of the clinicians in this area
Three of the authors (NEJ CC and EZ) created theinitial draft document drawing from the existing literatureand clinical practice that served as an initial text for the rec-ommendation developments
After creation of the single text stakeholders were engagedto refine the recommendations through a consensus-basedapproach The experts were initially assigned to specific areas ofrecommendations where they refined the recommendations Afacilitator (LH) then lead a series of meetings to review reviseand finalize the recommendations with the entire author panel
These efforts led to the final consensus-based care recom-mendations along with a quick reference guide The care rec-ommendations are divided into 2 main sections the GeneralCare Considerations and Systems-based Approach to Manage-ment Because there are differences between childhood-onsetand congenital-onset DM1 recommendations specific to CDMare separated throughout the document The Quick ReferenceGuide is provided as an appendix and the full document isavailable online (appendix e-1 linkslwwcomCPJA89) Bothfeature flowcharts and other infographics for ease of use
ResultsSee full recommendations at Neurologyorgcp
General care considerationsDiagnosis and classification
c The diagnosis of DM1 should be suspected in any childwith a family history of DM1 andor presenting withone or more of the following features Eyelid ptosis andor oral motor weakness Distal weakness primarily of the finger and wrist flexorswithout contractures or weakness of the neck flexors
Myotonia or ldquostiffnessrdquo of muscles Autistic features or social communication difficulties Attention deficit disorder anxiety and other behav-ioral problems
Developmental delay andor Intellectual disability
The age of onset of DM1 is variable
and intergenerational repeat
expansion (known as anticipation)
may result in symptom onset during
childhood
The multisystemic nature morbidity
and mortality associated with
congenital and childhood-onset
myotonic dystrophy necessitate the
development of care
recommendations to standardize and
improve the care of this population
444 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
Learning disabilities (eg dyslexia dyscalculia) Excessive daytime sleepiness (EDS) Gastrointestinal issues constipation or diarrhea Scoliosis Arrhythmia Prolonged recovery or respiratory arrest after anesthesia Neonatal features of hypotonia weakness club footrespiratory distress or feeding problems
c The classification of congenital and childhood-onsetDM1 is provided in table 1 in Quick Reference GuideNote that diagnosis may be made retrospectively afterreviewing symptom onset Fetal tissue with long CTGrepeats should not be called CDMbecause this diagnosisis reserved for newborns In these cases we wouldsuggest use of fetal DM1 as more appropriate
c Genetic counseling is recommended for patientsexhibiting clinical signs indicative of DM1 or have at-risk family members to enable them to make aninformed decision about whether to proceed to genetictesting Individuals with 37ndash49 CTG repeats aredeemed very unlikely to develop detectable DM1symptoms However such ldquopremutationsrdquo can expandinto the disease range in subsequent generationsparticularly when transmitted by women Individualsthus identified should be offered genetic counseling(see Genetic counseling) to discuss their risk fortransmitting DM1
Genetic counselingc Referral to genetic counseling (see nsgcorg) is recom-
mended for all patients with congenital and childhood-onset DM1 and their parents and to assess the parents forthe diagnosis of DM1
c Genetic counseling in affected families should conveyinformation about The inheritance pattern of disease (autosomal
dominant inheritance) The wide variability in the scope and severity of DM1
symptoms even within the same family The possibility of changes in symptom scope and
severity over time The likelihood that the mutation will expand and the
disease will become more severe as it is passed fromgeneration to generation (anticipation)
Particular attention to the possibility of a minimallyaffected mother giving birth to a severely affected child
Options for family planningc Do not use CTG repeat numbers if available for genetic
advice or prognostication these need to be discussedwith a genetic counselor Specifically repeat size may bean indicator of severity but it does not provide anyinformation about the prognosis
Focus on CDMc Once a family has had a child with CDM there is an
increased risk that the next affected child with DM1 islikely to have congenital form as well
Neonatal care A high-risk obstetrician should provide prenatal obstetric
care for mothers known or suspected to carry a child withDM1
Pediatric or neonatal specialist should be present atdelivery if a mother is known to have DM1 or if the childis known or suspected to have DM1
Focus on CDM Children with CDM will often need management in
a neonatal intensive care unit with the capability to dealwith breathing and feeding support This team requiresa range of neonatal and consulting specialists who canmanage the genetic respiratory gastrointestinal or-thopedic neuromuscular neurosurgical and cardiacissues See figure 1 in Quick Reference Guide forneonatal care
End of life counseling and management Recommend the introduction of palliative care at the
time of diagnosis and at regular intervals thereafter Whena formal pediatric palliative care team is available theyshould be consulted
Recognize and address caregiver burden whether thecaregiver has DM1 offering respite care or equivalentmeasures to patient to improve family support Addressnormal grief on the part of the patient and family andoffer counseling as appropriate
Establish an emergency health care plan and advancedirectives with the family
Focus on CDM Introduce the concept that the natural history of the
disease includes progressive improvement of strength forthe first decade of life however the complications ofCDM can be critical and have a high risk of mortalityparticularly in the first year of life
Advise families or caregivers that invasive and non-invasive ventilation (NIV) and nutrition through gastro-stomy tube are acceptable parts of care for patients withCDM
Surgery and anesthesia Inform all caregivers that anyone administering an
anesthetic should be aware of the DM1 diagnosis When possible combine procedures under a single
sedation Arrange for a preanesthetic visit for all children planning
to have deep sedation for a diagnostic test procedureor surgery If possible include a pulmonologist withexpertise in neuromuscular diseases during this visit
Even if the patient has mild DM1 monitoring for a longerperiod of time than is typical following anesthesia orsurgery will allow for identifying serious adverse events inthe hospital setting
Providers are encouraged to review the MyotonicDystrophy Foundation Practical Suggestions for the
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 445
Anesthetic Management of a Myotonic Dystrophy Patient(myotonicorgsitesdefaultfilesMDF_LongForm_AnesGuidelines_01Cpdf) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia and the Anesthesia Quick ReferenceGuide (myotonicorgsitesdefaultfilesMDF Anes-thesia Guidelines FNL 2016 2 2 pdf) These docu-ments should be reviewed before treatment decisions
Focus on CDM It is worth noting that children with CDM are at a higher
risk of anesthetic complications given the underlyingrespiratory involvement as opposed to those withchildhood-onset myotonic dystrophy
Systems-based approachto managementRespiratory Signs of respiratory problems in children with myotonic
dystrophy include ineffective cough recurrent pulmo-nary infections orthopnea dyspnea poor sleep morningheadaches apnea fatigue and snoring
See figure 2 in Quick Reference Guide for a flowchart oftesting and treatment options in congenital andchildhood-onset myotonic dystrophy
Focus on CDM For CDM children who remain on longer term trach
ventilation there is often improvement in respiratorystrength over time and consideration to decannulatea tracheostomy should be made after careful considerationwith the multidisciplinary team including neurologyrespirology ear nose and throat and the familyConsideration of airway control respiratory infectionfrequency ability to tolerate a facial or nasal mask for NIVand compliance and cooperation with maintenancepulmonary therapy such as cough assist breathe stakingetc Testing for hypoventilation in sleep should be donebefore decannulation
Cardiovascularc Inform families of the risks of arrhythmias and cardiac
dysfunction and the importance of prompt medicalattention if symptoms are observed (ie palpitationspresyncope syncope dyspnea chest pain unexplainedfatigue) A 12-lead ECG should be performed at DM1 diagnosisand if normal and the patient remains asymptomatic ECGshould be performed annually and warrants moreinvestigation if the patient is symptomatic
If the ECG is normal and clinical suspicion is high a24-hour Holter monitor may be considered asa second-line investigation
Because specific medications such as mexiletine andpsychostimulants are antiarrhythmic an ECG before
use again within 3 months of starting therapy andthen at serial intervals is recommended
Consider in-hospital cardiac monitoring to detectarrhythmias if admitted for longer duration thantypical after surgical procedures or if admitted due tosevere illness or infection
c For young DM1 patients serial exercise stress testingand signal-averaged ECGs may be considered
c Evaluate and treat using American Heart Association(AHA) Management of Cardiac Involvement AssociatedWith Neuromuscular Diseases A Scientific Statement Fromthe American Heart Association 2017 circahajournalsorgcontent13613e200long and ACC ([AmericanCollege of Cardiology]AHA)ESC (European Societyof Cardiology) Guidelines for Management of Patientswith Ventricular Arrhythmias and the Prevention of SuddenCardiac Death (see ncbinlmnihgovpubmed16949478)- section on pediatric issues 134
Skeletal muscle weakness orthopediccomplications and rehabilitation
c Children should be evaluated early and often forphysical occupational and speech therapy needs withspecific attention to Feeding concerns and dysphagia Gross motor delay Gross and fine motor weakness Dysarthria and potential augmentative and alternativecommunication needs
Language acquisition delaysc The spine should be assessed for scoliosis and if
necessary consider bracing or referral to orthopedicsurgeon
c Children should be encouraged to participate in speechtherapy targeting speech language and communicationfrom a very early age
Focus on CDM Newborns with CDM often having difficulty feeding and
alternative nutrition should be considered After abouta year of actively working with a speech therapist oroccupational therapist most children can generally starton oral feeding
Children with CDM experience progressive improve-ment in their proximal strength until adolescence ata minimum Therefore children should be encouraged toparticipate in physical activities
Prevention of joint contractures are key to managementand should be closely monitored with early initiation ofstretching Treatment of talipes equinovarus and otherjoint contractures should include initial stretchingregimen and appropriate ankle bracing (for talipesequinovarus) Serial casting may be considered
Skeletal muscle myotoniac Delayed relaxation after grip or percussion difficulty
related to activities of daily life progressive speech
446 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
impairment or profound irritable bowel symptoms aresigns often related to myotonia
c Mexiletine (Mexitil) is an option for myotonia if it isdemonstrated and is distressing to the patient Mexiletinemay not be approved for use in every country In these casesother sodium channel antagonists may be considered Because mexiletine is an antiarrhythmic an ECG
before use again within 3 months of starting therapyand then at serial intervals is recommended
Instruct the patient to avoid dyspepsia and transientldquodizzy feelingsrdquo associated with mexiletine treatmentby taking it with food to extend absorption and lowerpeak level in blood
Ocular and hearing management Baseline audiometry should be performed especially at
school age Ophthalmologic assessment should be performed at
diagnosis and at least yearly to evaluate for hyperopiastigmatism strabismus and visual acuity to preventevolution of visual impairment
Eyelid ptosis if ptosis becomes severe and interferes withvision intervention such as eyelid ldquocrutchesrdquo that can beinserted into glasses may be warranted Try crutches asa remedy for ptosis before eyelid surgery is consideredbecause of anesthesia risks Ophthalmic lubricants for dryeye may be considered
Gastrointestinal andgenitourinary management
c Presence of gastrointestinal symptoms such as abdom-inal pain constipation fecal incontinence or diarrheamay be a frequent problem The symptoms may mimicirritable bowel syndrome (IBS)15 Fiber supplementa-tion (more than 8 g daily) is the first-line treatment
c Gentle laxatives (see below) for constipation Oilsshould be avoided as they will lead to diarrhea Ifa patient does not respond to the first- or second-linerecommendations below a referral to a gastrointestinalspecialist for anal manometry should be considered First-line therapy recommendations polyethylene
glycol (Miralax) senna (Ex-Lax Senokot) docusate(Colace) or lactulose (Cholac)
Second-line therapy recommendations bisacodyl(Dulcolax Correctol) lubiprostone (Amitiza) orlinaclotide (Linzess)
Metoclopramide (Reglan) may be used to reduce thesymptoms of gastroparesis pseudo-obstruction andgastric reflux Providers should be aware of the risk ofacute dystonic reactions with this medication Long-term use is not recommended because this drug cancause tardive dyskinesia
Cholestyramine and loperamide are other options inthe presence of mainly diarrhea and anticholinergicdrug such as hyoscyamine sulfate in the presence ofIBS Because anticholinergic drugs may be antiar-rhythmic see Cardiac section on management
Mexiletine may be considered for refractory diarrheaor constipation because the drug may be antiarrhyth-mic see Cardiac section on management
c If bacterial overgrowth is found on breath testingtreating with antibiotics may reduce diarrhea
Focus on CDM As mentioned in the neonatal care section children with
CDMmay require a temporary feeding tube If dysphagiapersists consider enteral nutrition Refer to speech therapyChildren should be periodically re-assessed for improvingdysphagia
Children with CDMoften benefit from dysphagia therapyWith aggressive dysphagia therapy children with CDMoften are able to feed orally within the first year of life
Neurodevelopmental managementRecommendations
c Neuropsychological testing should be performed inevery child with DM1 to delineate cognitive strengthsand weaknesses This may include the following Psychometric assessment of global intellectual abilityand adaptive functioning
Assessment of executive functions Assessment of social cognition Assessment of visuomotor integration and visuospatialability
Assessment of receptive and expressive language abilities Assessment of EDS Assessment of learning disabilities (specific tests fordyscalculia dyslexia and dyspraxia)
c The assessments should be performed in the congenitalform in preschool age and should be repeated depend-ing on the level of functioning 2ndash3 times beforeadulthood In childhood DM1 neuropsychologicaltesting is recommended at diagnosis and repeated inpreschool or school age and college period
c Patients with psychiatric or behavioral issues should bereferred to a mental health care professional forassessment of Autism Spectrum Disorders AttentionDeficit disorders with or without Hyperactivity alex-iythmia and other behavioral problems
c Psychostimulants may be beneficial if attention deficitsare associated with an impairing level of fatigue or EDS(see excessive daytime sleepiness) As psychostimulantsmay be proarrhythmic see Cardiac section on stimulantmanagementSerotonin-enhancing antidepressants if excessive anxietyor other treatable psychiatric symptoms are present
Specific cognitive remediation programs to enhance socialemotional abilities (visual contact joint attention emotionalregulation) or executive functions efficiency (inhibitorycontrol attention working memory and cognitive flexibil-ity) using dedicated software (eg Cogmedreg)
c Language remediation and reading therapy should beconsidered because of the presence of cognitive deficitseven in children with normal intelligence Attention deficit
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 447
fatigability and visualndashspatial construction dysfunctioncan result in specific learning disorders with impair-ment in reading and spelling as well as in mathematics
Psychosocial management Healthcare professionals have a responsibility to co-
ordinate specialist care and support services for childrenwith DM1 There is a need to be alert to the psychologicaland social dysfunctions and monitor home and educa-tional circumstances Liaison between agencies is essentialto ensure a consistent approach between health educationand social care agencies
Children with DM1 should have access to appropriatepsychological and therapy services at an early age to ensurethey are fulfilling their maximum potential and learningcoping strategies for later life The modification of activitiesincluding social engagement strategies would providea foundation for each child to grow in confidence and esteem
Family care and support is essential throughout child-hood with support and social care assistance whererequired Schools should be provided with specialistinformation about the care and management of a childwith DM1 A social work consult or a referral to nursingcase management can also be beneficial for patients Aholistic approach is critical because the affected parentmay also need additional assistance
Families should have access to disability benefitsadequate housing and adaptations during the progressionof the condition
Excessive daytime sleepiness Family members and educators should be educated about
the EDS that comes with DM1 Children should be screened for signs of EDS including
prolonged naps or falling asleep in school Possible sleep apnea should be evaluated with overnight
oximetry or polysomnogram Positive-pressure ventilation can be considered if a DM1
patientrsquos sleepiness is thought to be related to nocturnalor daytime hypoventilation or sleep apnea Patientsshould be referred to pulmonologists who have experi-ence in neuromuscular diseases for consideration ofassisted ventilation
Stimulant therapy with a psychostimulant such asmodafinil (Provigil) methylphenidate or other stimulantcan be considered if central hypersomnia is suspectedOften difficulty staying awake in school is a triggeringfactor Special care should be taken in children withpreviously detected cardiac arrhythmia (See Cardiacsection on stimulant management)
Endocrine and metabolismc DM1 male patients should undergo a detailed physical
examination in search of gonadal atrophy or cryptorchidismc Patients should have a HbA1c and thyroid-stimulating
hormone and Free T4 level measured at baseline andevery 3 years or if there is a clinical suspicion
c Adolescent patients should be screened as adult patients Gonadal insufficiency and complications of the
reproductive system Inquiring about amenorrheaor dysmenorrhea for the female patients and erectiledysfunction for male patients
Fasting blood lipids plasma glucose liver enzymesbilirubin levels and gamma-glutamyl transpeptidaseshould be measured at baseline
ConclusionsThe recommendations for care of congenital and childhood-onset myotonic dystrophy have been created by consensus ofclinicians experienced in their care management Given theabsence of rigorous studies in many of these areas theseguidelines were created by consensus They are designed tostandardize the care of children with a multisystemic disorderthat leads to significant morbidity and mortality
Study fundingMyotonic Dystrophy Foundation
DisclosureN Johnson serves on the scientific advisory boards ofCytokinetics AveXis AMO Pharma and Biogen Idec hasreceived funding for travel andor speaker honoraria fromStrongbridge serves as a consultant for AMO PharmaAveXis and Vertex Pharma and receives research supportfrom Ionis Pharmaceuticals Biogen Idec Valerion Thera-peutics Cytokinetics Acceleron AveXis AMO PharmaNIHNINDS FDA Muscular Dystrophy Association andMyotonic Dystrophy Foundation EZ Aldana and NAngeard report no disclosures T Ashizawa serves on sci-entific advisory boards for the Myotonic Dystrophy Foun-dation NIH and National Ataxia Foundation has receivedfunding for travel from Biohaven PacBio and NIHreceives research support from Myotonic DystrophyFoundation National Ataxia Foundation Biohaven Phar-maceuticals Biogen andNIHNINDS and is a professor atWeill Cornell Medical College adjunct professor at BaylorCollege of Medicine guest faculty at Central South Uni-versity China KN Berggren serves on the scientific advi-sory board of Biogen and receives funding for travel andorspeaker honoraria from HDSA and FSH Society C Marini-Bettolo has served on the scientific advisory boards ofAvexis and Biogen T Duong A-B Ekstrom V Sansone CTian and L Hellerstein report no disclosures C Campbellserves on the scientific advisory boards of Catabasis andPTC Therapeutics and receives research support fromValerion Pharmaceuticals PTC Therapeutics Pfizer IonisEli Lilly Prosensa Child Health Foundation and JessersquosJourney Foundation Full disclosure form informationprovided by the authors is available with the full text of thisarticle at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 21 2018 Accepted infinal form March 4 2019
448 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
Appendix Authors
Name Location Role Contribution
Nicholas EJohnson MDMCSI
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscriptpublication of thedraft and revision
EugenioZapataAldana MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NathalieAngeard PhD
Inserm ampUniversity of ParisDescartes ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
TetsuoAshizawa MD
HoustonMethodistNeurologicalInstitute Texas
Author Data acquisitiondrafting andrevision of themanuscript
Kiera NBerggren MACCC-SLP MS
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscript
Chiara Marini-Bettolo MDPhD
Institute of GeneticMedicineNewcastleUniversity andNewcastle uponTyne HospitalsNHS FoundationTrust Newcastleupon Tyne UK
Author Data acquisitiondrafting andrevision of themanuscript
Appendix (continued)
Name Location Role Contribution
Tina DuongMPT PhD
StanfordUniversity CA
Author Data acquisitiondrafting andrevision of themanuscript
Anne-BeritEkstrom MDPhD
Queen SilviaChildrenrsquo sHospitalGothenburgSweden
Author Data acquisitiondrafting andrevision of themanuscript
ValeriaSansone MD
NEMO ClinicMilan Italy
Author Data acquisitiondrafting andrevision of themanuscript
Cuixia TianMD
CincinnatiChildrenrsquos HospitalMedical CenterCincinnati OH
Author Data acquisitiondrafting andrevision of themanuscript
LeahHellersteinLCSW MPH
MyotonicDystrophyFoundation SanFrancisco CA
CorrespondingAuthor
Obtaining fundingdrafting andreviewing themanuscript studyconcept anddesign
CraigCampbell MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 449
450 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 451
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
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bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
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reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
Learning disabilities (eg dyslexia dyscalculia) Excessive daytime sleepiness (EDS) Gastrointestinal issues constipation or diarrhea Scoliosis Arrhythmia Prolonged recovery or respiratory arrest after anesthesia Neonatal features of hypotonia weakness club footrespiratory distress or feeding problems
c The classification of congenital and childhood-onsetDM1 is provided in table 1 in Quick Reference GuideNote that diagnosis may be made retrospectively afterreviewing symptom onset Fetal tissue with long CTGrepeats should not be called CDMbecause this diagnosisis reserved for newborns In these cases we wouldsuggest use of fetal DM1 as more appropriate
c Genetic counseling is recommended for patientsexhibiting clinical signs indicative of DM1 or have at-risk family members to enable them to make aninformed decision about whether to proceed to genetictesting Individuals with 37ndash49 CTG repeats aredeemed very unlikely to develop detectable DM1symptoms However such ldquopremutationsrdquo can expandinto the disease range in subsequent generationsparticularly when transmitted by women Individualsthus identified should be offered genetic counseling(see Genetic counseling) to discuss their risk fortransmitting DM1
Genetic counselingc Referral to genetic counseling (see nsgcorg) is recom-
mended for all patients with congenital and childhood-onset DM1 and their parents and to assess the parents forthe diagnosis of DM1
c Genetic counseling in affected families should conveyinformation about The inheritance pattern of disease (autosomal
dominant inheritance) The wide variability in the scope and severity of DM1
symptoms even within the same family The possibility of changes in symptom scope and
severity over time The likelihood that the mutation will expand and the
disease will become more severe as it is passed fromgeneration to generation (anticipation)
Particular attention to the possibility of a minimallyaffected mother giving birth to a severely affected child
Options for family planningc Do not use CTG repeat numbers if available for genetic
advice or prognostication these need to be discussedwith a genetic counselor Specifically repeat size may bean indicator of severity but it does not provide anyinformation about the prognosis
Focus on CDMc Once a family has had a child with CDM there is an
increased risk that the next affected child with DM1 islikely to have congenital form as well
Neonatal care A high-risk obstetrician should provide prenatal obstetric
care for mothers known or suspected to carry a child withDM1
Pediatric or neonatal specialist should be present atdelivery if a mother is known to have DM1 or if the childis known or suspected to have DM1
Focus on CDM Children with CDM will often need management in
a neonatal intensive care unit with the capability to dealwith breathing and feeding support This team requiresa range of neonatal and consulting specialists who canmanage the genetic respiratory gastrointestinal or-thopedic neuromuscular neurosurgical and cardiacissues See figure 1 in Quick Reference Guide forneonatal care
End of life counseling and management Recommend the introduction of palliative care at the
time of diagnosis and at regular intervals thereafter Whena formal pediatric palliative care team is available theyshould be consulted
Recognize and address caregiver burden whether thecaregiver has DM1 offering respite care or equivalentmeasures to patient to improve family support Addressnormal grief on the part of the patient and family andoffer counseling as appropriate
Establish an emergency health care plan and advancedirectives with the family
Focus on CDM Introduce the concept that the natural history of the
disease includes progressive improvement of strength forthe first decade of life however the complications ofCDM can be critical and have a high risk of mortalityparticularly in the first year of life
Advise families or caregivers that invasive and non-invasive ventilation (NIV) and nutrition through gastro-stomy tube are acceptable parts of care for patients withCDM
Surgery and anesthesia Inform all caregivers that anyone administering an
anesthetic should be aware of the DM1 diagnosis When possible combine procedures under a single
sedation Arrange for a preanesthetic visit for all children planning
to have deep sedation for a diagnostic test procedureor surgery If possible include a pulmonologist withexpertise in neuromuscular diseases during this visit
Even if the patient has mild DM1 monitoring for a longerperiod of time than is typical following anesthesia orsurgery will allow for identifying serious adverse events inthe hospital setting
Providers are encouraged to review the MyotonicDystrophy Foundation Practical Suggestions for the
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 445
Anesthetic Management of a Myotonic Dystrophy Patient(myotonicorgsitesdefaultfilesMDF_LongForm_AnesGuidelines_01Cpdf) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia and the Anesthesia Quick ReferenceGuide (myotonicorgsitesdefaultfilesMDF Anes-thesia Guidelines FNL 2016 2 2 pdf) These docu-ments should be reviewed before treatment decisions
Focus on CDM It is worth noting that children with CDM are at a higher
risk of anesthetic complications given the underlyingrespiratory involvement as opposed to those withchildhood-onset myotonic dystrophy
Systems-based approachto managementRespiratory Signs of respiratory problems in children with myotonic
dystrophy include ineffective cough recurrent pulmo-nary infections orthopnea dyspnea poor sleep morningheadaches apnea fatigue and snoring
See figure 2 in Quick Reference Guide for a flowchart oftesting and treatment options in congenital andchildhood-onset myotonic dystrophy
Focus on CDM For CDM children who remain on longer term trach
ventilation there is often improvement in respiratorystrength over time and consideration to decannulatea tracheostomy should be made after careful considerationwith the multidisciplinary team including neurologyrespirology ear nose and throat and the familyConsideration of airway control respiratory infectionfrequency ability to tolerate a facial or nasal mask for NIVand compliance and cooperation with maintenancepulmonary therapy such as cough assist breathe stakingetc Testing for hypoventilation in sleep should be donebefore decannulation
Cardiovascularc Inform families of the risks of arrhythmias and cardiac
dysfunction and the importance of prompt medicalattention if symptoms are observed (ie palpitationspresyncope syncope dyspnea chest pain unexplainedfatigue) A 12-lead ECG should be performed at DM1 diagnosisand if normal and the patient remains asymptomatic ECGshould be performed annually and warrants moreinvestigation if the patient is symptomatic
If the ECG is normal and clinical suspicion is high a24-hour Holter monitor may be considered asa second-line investigation
Because specific medications such as mexiletine andpsychostimulants are antiarrhythmic an ECG before
use again within 3 months of starting therapy andthen at serial intervals is recommended
Consider in-hospital cardiac monitoring to detectarrhythmias if admitted for longer duration thantypical after surgical procedures or if admitted due tosevere illness or infection
c For young DM1 patients serial exercise stress testingand signal-averaged ECGs may be considered
c Evaluate and treat using American Heart Association(AHA) Management of Cardiac Involvement AssociatedWith Neuromuscular Diseases A Scientific Statement Fromthe American Heart Association 2017 circahajournalsorgcontent13613e200long and ACC ([AmericanCollege of Cardiology]AHA)ESC (European Societyof Cardiology) Guidelines for Management of Patientswith Ventricular Arrhythmias and the Prevention of SuddenCardiac Death (see ncbinlmnihgovpubmed16949478)- section on pediatric issues 134
Skeletal muscle weakness orthopediccomplications and rehabilitation
c Children should be evaluated early and often forphysical occupational and speech therapy needs withspecific attention to Feeding concerns and dysphagia Gross motor delay Gross and fine motor weakness Dysarthria and potential augmentative and alternativecommunication needs
Language acquisition delaysc The spine should be assessed for scoliosis and if
necessary consider bracing or referral to orthopedicsurgeon
c Children should be encouraged to participate in speechtherapy targeting speech language and communicationfrom a very early age
Focus on CDM Newborns with CDM often having difficulty feeding and
alternative nutrition should be considered After abouta year of actively working with a speech therapist oroccupational therapist most children can generally starton oral feeding
Children with CDM experience progressive improve-ment in their proximal strength until adolescence ata minimum Therefore children should be encouraged toparticipate in physical activities
Prevention of joint contractures are key to managementand should be closely monitored with early initiation ofstretching Treatment of talipes equinovarus and otherjoint contractures should include initial stretchingregimen and appropriate ankle bracing (for talipesequinovarus) Serial casting may be considered
Skeletal muscle myotoniac Delayed relaxation after grip or percussion difficulty
related to activities of daily life progressive speech
446 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
impairment or profound irritable bowel symptoms aresigns often related to myotonia
c Mexiletine (Mexitil) is an option for myotonia if it isdemonstrated and is distressing to the patient Mexiletinemay not be approved for use in every country In these casesother sodium channel antagonists may be considered Because mexiletine is an antiarrhythmic an ECG
before use again within 3 months of starting therapyand then at serial intervals is recommended
Instruct the patient to avoid dyspepsia and transientldquodizzy feelingsrdquo associated with mexiletine treatmentby taking it with food to extend absorption and lowerpeak level in blood
Ocular and hearing management Baseline audiometry should be performed especially at
school age Ophthalmologic assessment should be performed at
diagnosis and at least yearly to evaluate for hyperopiastigmatism strabismus and visual acuity to preventevolution of visual impairment
Eyelid ptosis if ptosis becomes severe and interferes withvision intervention such as eyelid ldquocrutchesrdquo that can beinserted into glasses may be warranted Try crutches asa remedy for ptosis before eyelid surgery is consideredbecause of anesthesia risks Ophthalmic lubricants for dryeye may be considered
Gastrointestinal andgenitourinary management
c Presence of gastrointestinal symptoms such as abdom-inal pain constipation fecal incontinence or diarrheamay be a frequent problem The symptoms may mimicirritable bowel syndrome (IBS)15 Fiber supplementa-tion (more than 8 g daily) is the first-line treatment
c Gentle laxatives (see below) for constipation Oilsshould be avoided as they will lead to diarrhea Ifa patient does not respond to the first- or second-linerecommendations below a referral to a gastrointestinalspecialist for anal manometry should be considered First-line therapy recommendations polyethylene
glycol (Miralax) senna (Ex-Lax Senokot) docusate(Colace) or lactulose (Cholac)
Second-line therapy recommendations bisacodyl(Dulcolax Correctol) lubiprostone (Amitiza) orlinaclotide (Linzess)
Metoclopramide (Reglan) may be used to reduce thesymptoms of gastroparesis pseudo-obstruction andgastric reflux Providers should be aware of the risk ofacute dystonic reactions with this medication Long-term use is not recommended because this drug cancause tardive dyskinesia
Cholestyramine and loperamide are other options inthe presence of mainly diarrhea and anticholinergicdrug such as hyoscyamine sulfate in the presence ofIBS Because anticholinergic drugs may be antiar-rhythmic see Cardiac section on management
Mexiletine may be considered for refractory diarrheaor constipation because the drug may be antiarrhyth-mic see Cardiac section on management
c If bacterial overgrowth is found on breath testingtreating with antibiotics may reduce diarrhea
Focus on CDM As mentioned in the neonatal care section children with
CDMmay require a temporary feeding tube If dysphagiapersists consider enteral nutrition Refer to speech therapyChildren should be periodically re-assessed for improvingdysphagia
Children with CDMoften benefit from dysphagia therapyWith aggressive dysphagia therapy children with CDMoften are able to feed orally within the first year of life
Neurodevelopmental managementRecommendations
c Neuropsychological testing should be performed inevery child with DM1 to delineate cognitive strengthsand weaknesses This may include the following Psychometric assessment of global intellectual abilityand adaptive functioning
Assessment of executive functions Assessment of social cognition Assessment of visuomotor integration and visuospatialability
Assessment of receptive and expressive language abilities Assessment of EDS Assessment of learning disabilities (specific tests fordyscalculia dyslexia and dyspraxia)
c The assessments should be performed in the congenitalform in preschool age and should be repeated depend-ing on the level of functioning 2ndash3 times beforeadulthood In childhood DM1 neuropsychologicaltesting is recommended at diagnosis and repeated inpreschool or school age and college period
c Patients with psychiatric or behavioral issues should bereferred to a mental health care professional forassessment of Autism Spectrum Disorders AttentionDeficit disorders with or without Hyperactivity alex-iythmia and other behavioral problems
c Psychostimulants may be beneficial if attention deficitsare associated with an impairing level of fatigue or EDS(see excessive daytime sleepiness) As psychostimulantsmay be proarrhythmic see Cardiac section on stimulantmanagementSerotonin-enhancing antidepressants if excessive anxietyor other treatable psychiatric symptoms are present
Specific cognitive remediation programs to enhance socialemotional abilities (visual contact joint attention emotionalregulation) or executive functions efficiency (inhibitorycontrol attention working memory and cognitive flexibil-ity) using dedicated software (eg Cogmedreg)
c Language remediation and reading therapy should beconsidered because of the presence of cognitive deficitseven in children with normal intelligence Attention deficit
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 447
fatigability and visualndashspatial construction dysfunctioncan result in specific learning disorders with impair-ment in reading and spelling as well as in mathematics
Psychosocial management Healthcare professionals have a responsibility to co-
ordinate specialist care and support services for childrenwith DM1 There is a need to be alert to the psychologicaland social dysfunctions and monitor home and educa-tional circumstances Liaison between agencies is essentialto ensure a consistent approach between health educationand social care agencies
Children with DM1 should have access to appropriatepsychological and therapy services at an early age to ensurethey are fulfilling their maximum potential and learningcoping strategies for later life The modification of activitiesincluding social engagement strategies would providea foundation for each child to grow in confidence and esteem
Family care and support is essential throughout child-hood with support and social care assistance whererequired Schools should be provided with specialistinformation about the care and management of a childwith DM1 A social work consult or a referral to nursingcase management can also be beneficial for patients Aholistic approach is critical because the affected parentmay also need additional assistance
Families should have access to disability benefitsadequate housing and adaptations during the progressionof the condition
Excessive daytime sleepiness Family members and educators should be educated about
the EDS that comes with DM1 Children should be screened for signs of EDS including
prolonged naps or falling asleep in school Possible sleep apnea should be evaluated with overnight
oximetry or polysomnogram Positive-pressure ventilation can be considered if a DM1
patientrsquos sleepiness is thought to be related to nocturnalor daytime hypoventilation or sleep apnea Patientsshould be referred to pulmonologists who have experi-ence in neuromuscular diseases for consideration ofassisted ventilation
Stimulant therapy with a psychostimulant such asmodafinil (Provigil) methylphenidate or other stimulantcan be considered if central hypersomnia is suspectedOften difficulty staying awake in school is a triggeringfactor Special care should be taken in children withpreviously detected cardiac arrhythmia (See Cardiacsection on stimulant management)
Endocrine and metabolismc DM1 male patients should undergo a detailed physical
examination in search of gonadal atrophy or cryptorchidismc Patients should have a HbA1c and thyroid-stimulating
hormone and Free T4 level measured at baseline andevery 3 years or if there is a clinical suspicion
c Adolescent patients should be screened as adult patients Gonadal insufficiency and complications of the
reproductive system Inquiring about amenorrheaor dysmenorrhea for the female patients and erectiledysfunction for male patients
Fasting blood lipids plasma glucose liver enzymesbilirubin levels and gamma-glutamyl transpeptidaseshould be measured at baseline
ConclusionsThe recommendations for care of congenital and childhood-onset myotonic dystrophy have been created by consensus ofclinicians experienced in their care management Given theabsence of rigorous studies in many of these areas theseguidelines were created by consensus They are designed tostandardize the care of children with a multisystemic disorderthat leads to significant morbidity and mortality
Study fundingMyotonic Dystrophy Foundation
DisclosureN Johnson serves on the scientific advisory boards ofCytokinetics AveXis AMO Pharma and Biogen Idec hasreceived funding for travel andor speaker honoraria fromStrongbridge serves as a consultant for AMO PharmaAveXis and Vertex Pharma and receives research supportfrom Ionis Pharmaceuticals Biogen Idec Valerion Thera-peutics Cytokinetics Acceleron AveXis AMO PharmaNIHNINDS FDA Muscular Dystrophy Association andMyotonic Dystrophy Foundation EZ Aldana and NAngeard report no disclosures T Ashizawa serves on sci-entific advisory boards for the Myotonic Dystrophy Foun-dation NIH and National Ataxia Foundation has receivedfunding for travel from Biohaven PacBio and NIHreceives research support from Myotonic DystrophyFoundation National Ataxia Foundation Biohaven Phar-maceuticals Biogen andNIHNINDS and is a professor atWeill Cornell Medical College adjunct professor at BaylorCollege of Medicine guest faculty at Central South Uni-versity China KN Berggren serves on the scientific advi-sory board of Biogen and receives funding for travel andorspeaker honoraria from HDSA and FSH Society C Marini-Bettolo has served on the scientific advisory boards ofAvexis and Biogen T Duong A-B Ekstrom V Sansone CTian and L Hellerstein report no disclosures C Campbellserves on the scientific advisory boards of Catabasis andPTC Therapeutics and receives research support fromValerion Pharmaceuticals PTC Therapeutics Pfizer IonisEli Lilly Prosensa Child Health Foundation and JessersquosJourney Foundation Full disclosure form informationprovided by the authors is available with the full text of thisarticle at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 21 2018 Accepted infinal form March 4 2019
448 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
Appendix Authors
Name Location Role Contribution
Nicholas EJohnson MDMCSI
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscriptpublication of thedraft and revision
EugenioZapataAldana MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NathalieAngeard PhD
Inserm ampUniversity of ParisDescartes ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
TetsuoAshizawa MD
HoustonMethodistNeurologicalInstitute Texas
Author Data acquisitiondrafting andrevision of themanuscript
Kiera NBerggren MACCC-SLP MS
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscript
Chiara Marini-Bettolo MDPhD
Institute of GeneticMedicineNewcastleUniversity andNewcastle uponTyne HospitalsNHS FoundationTrust Newcastleupon Tyne UK
Author Data acquisitiondrafting andrevision of themanuscript
Appendix (continued)
Name Location Role Contribution
Tina DuongMPT PhD
StanfordUniversity CA
Author Data acquisitiondrafting andrevision of themanuscript
Anne-BeritEkstrom MDPhD
Queen SilviaChildrenrsquo sHospitalGothenburgSweden
Author Data acquisitiondrafting andrevision of themanuscript
ValeriaSansone MD
NEMO ClinicMilan Italy
Author Data acquisitiondrafting andrevision of themanuscript
Cuixia TianMD
CincinnatiChildrenrsquos HospitalMedical CenterCincinnati OH
Author Data acquisitiondrafting andrevision of themanuscript
LeahHellersteinLCSW MPH
MyotonicDystrophyFoundation SanFrancisco CA
CorrespondingAuthor
Obtaining fundingdrafting andreviewing themanuscript studyconcept anddesign
CraigCampbell MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 449
450 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 451
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
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httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
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httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
Anesthetic Management of a Myotonic Dystrophy Patient(myotonicorgsitesdefaultfilesMDF_LongForm_AnesGuidelines_01Cpdf) for anesthesia risks andrecommendations before any surgeries or proceduresrequiring anesthesia and the Anesthesia Quick ReferenceGuide (myotonicorgsitesdefaultfilesMDF Anes-thesia Guidelines FNL 2016 2 2 pdf) These docu-ments should be reviewed before treatment decisions
Focus on CDM It is worth noting that children with CDM are at a higher
risk of anesthetic complications given the underlyingrespiratory involvement as opposed to those withchildhood-onset myotonic dystrophy
Systems-based approachto managementRespiratory Signs of respiratory problems in children with myotonic
dystrophy include ineffective cough recurrent pulmo-nary infections orthopnea dyspnea poor sleep morningheadaches apnea fatigue and snoring
See figure 2 in Quick Reference Guide for a flowchart oftesting and treatment options in congenital andchildhood-onset myotonic dystrophy
Focus on CDM For CDM children who remain on longer term trach
ventilation there is often improvement in respiratorystrength over time and consideration to decannulatea tracheostomy should be made after careful considerationwith the multidisciplinary team including neurologyrespirology ear nose and throat and the familyConsideration of airway control respiratory infectionfrequency ability to tolerate a facial or nasal mask for NIVand compliance and cooperation with maintenancepulmonary therapy such as cough assist breathe stakingetc Testing for hypoventilation in sleep should be donebefore decannulation
Cardiovascularc Inform families of the risks of arrhythmias and cardiac
dysfunction and the importance of prompt medicalattention if symptoms are observed (ie palpitationspresyncope syncope dyspnea chest pain unexplainedfatigue) A 12-lead ECG should be performed at DM1 diagnosisand if normal and the patient remains asymptomatic ECGshould be performed annually and warrants moreinvestigation if the patient is symptomatic
If the ECG is normal and clinical suspicion is high a24-hour Holter monitor may be considered asa second-line investigation
Because specific medications such as mexiletine andpsychostimulants are antiarrhythmic an ECG before
use again within 3 months of starting therapy andthen at serial intervals is recommended
Consider in-hospital cardiac monitoring to detectarrhythmias if admitted for longer duration thantypical after surgical procedures or if admitted due tosevere illness or infection
c For young DM1 patients serial exercise stress testingand signal-averaged ECGs may be considered
c Evaluate and treat using American Heart Association(AHA) Management of Cardiac Involvement AssociatedWith Neuromuscular Diseases A Scientific Statement Fromthe American Heart Association 2017 circahajournalsorgcontent13613e200long and ACC ([AmericanCollege of Cardiology]AHA)ESC (European Societyof Cardiology) Guidelines for Management of Patientswith Ventricular Arrhythmias and the Prevention of SuddenCardiac Death (see ncbinlmnihgovpubmed16949478)- section on pediatric issues 134
Skeletal muscle weakness orthopediccomplications and rehabilitation
c Children should be evaluated early and often forphysical occupational and speech therapy needs withspecific attention to Feeding concerns and dysphagia Gross motor delay Gross and fine motor weakness Dysarthria and potential augmentative and alternativecommunication needs
Language acquisition delaysc The spine should be assessed for scoliosis and if
necessary consider bracing or referral to orthopedicsurgeon
c Children should be encouraged to participate in speechtherapy targeting speech language and communicationfrom a very early age
Focus on CDM Newborns with CDM often having difficulty feeding and
alternative nutrition should be considered After abouta year of actively working with a speech therapist oroccupational therapist most children can generally starton oral feeding
Children with CDM experience progressive improve-ment in their proximal strength until adolescence ata minimum Therefore children should be encouraged toparticipate in physical activities
Prevention of joint contractures are key to managementand should be closely monitored with early initiation ofstretching Treatment of talipes equinovarus and otherjoint contractures should include initial stretchingregimen and appropriate ankle bracing (for talipesequinovarus) Serial casting may be considered
Skeletal muscle myotoniac Delayed relaxation after grip or percussion difficulty
related to activities of daily life progressive speech
446 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
impairment or profound irritable bowel symptoms aresigns often related to myotonia
c Mexiletine (Mexitil) is an option for myotonia if it isdemonstrated and is distressing to the patient Mexiletinemay not be approved for use in every country In these casesother sodium channel antagonists may be considered Because mexiletine is an antiarrhythmic an ECG
before use again within 3 months of starting therapyand then at serial intervals is recommended
Instruct the patient to avoid dyspepsia and transientldquodizzy feelingsrdquo associated with mexiletine treatmentby taking it with food to extend absorption and lowerpeak level in blood
Ocular and hearing management Baseline audiometry should be performed especially at
school age Ophthalmologic assessment should be performed at
diagnosis and at least yearly to evaluate for hyperopiastigmatism strabismus and visual acuity to preventevolution of visual impairment
Eyelid ptosis if ptosis becomes severe and interferes withvision intervention such as eyelid ldquocrutchesrdquo that can beinserted into glasses may be warranted Try crutches asa remedy for ptosis before eyelid surgery is consideredbecause of anesthesia risks Ophthalmic lubricants for dryeye may be considered
Gastrointestinal andgenitourinary management
c Presence of gastrointestinal symptoms such as abdom-inal pain constipation fecal incontinence or diarrheamay be a frequent problem The symptoms may mimicirritable bowel syndrome (IBS)15 Fiber supplementa-tion (more than 8 g daily) is the first-line treatment
c Gentle laxatives (see below) for constipation Oilsshould be avoided as they will lead to diarrhea Ifa patient does not respond to the first- or second-linerecommendations below a referral to a gastrointestinalspecialist for anal manometry should be considered First-line therapy recommendations polyethylene
glycol (Miralax) senna (Ex-Lax Senokot) docusate(Colace) or lactulose (Cholac)
Second-line therapy recommendations bisacodyl(Dulcolax Correctol) lubiprostone (Amitiza) orlinaclotide (Linzess)
Metoclopramide (Reglan) may be used to reduce thesymptoms of gastroparesis pseudo-obstruction andgastric reflux Providers should be aware of the risk ofacute dystonic reactions with this medication Long-term use is not recommended because this drug cancause tardive dyskinesia
Cholestyramine and loperamide are other options inthe presence of mainly diarrhea and anticholinergicdrug such as hyoscyamine sulfate in the presence ofIBS Because anticholinergic drugs may be antiar-rhythmic see Cardiac section on management
Mexiletine may be considered for refractory diarrheaor constipation because the drug may be antiarrhyth-mic see Cardiac section on management
c If bacterial overgrowth is found on breath testingtreating with antibiotics may reduce diarrhea
Focus on CDM As mentioned in the neonatal care section children with
CDMmay require a temporary feeding tube If dysphagiapersists consider enteral nutrition Refer to speech therapyChildren should be periodically re-assessed for improvingdysphagia
Children with CDMoften benefit from dysphagia therapyWith aggressive dysphagia therapy children with CDMoften are able to feed orally within the first year of life
Neurodevelopmental managementRecommendations
c Neuropsychological testing should be performed inevery child with DM1 to delineate cognitive strengthsand weaknesses This may include the following Psychometric assessment of global intellectual abilityand adaptive functioning
Assessment of executive functions Assessment of social cognition Assessment of visuomotor integration and visuospatialability
Assessment of receptive and expressive language abilities Assessment of EDS Assessment of learning disabilities (specific tests fordyscalculia dyslexia and dyspraxia)
c The assessments should be performed in the congenitalform in preschool age and should be repeated depend-ing on the level of functioning 2ndash3 times beforeadulthood In childhood DM1 neuropsychologicaltesting is recommended at diagnosis and repeated inpreschool or school age and college period
c Patients with psychiatric or behavioral issues should bereferred to a mental health care professional forassessment of Autism Spectrum Disorders AttentionDeficit disorders with or without Hyperactivity alex-iythmia and other behavioral problems
c Psychostimulants may be beneficial if attention deficitsare associated with an impairing level of fatigue or EDS(see excessive daytime sleepiness) As psychostimulantsmay be proarrhythmic see Cardiac section on stimulantmanagementSerotonin-enhancing antidepressants if excessive anxietyor other treatable psychiatric symptoms are present
Specific cognitive remediation programs to enhance socialemotional abilities (visual contact joint attention emotionalregulation) or executive functions efficiency (inhibitorycontrol attention working memory and cognitive flexibil-ity) using dedicated software (eg Cogmedreg)
c Language remediation and reading therapy should beconsidered because of the presence of cognitive deficitseven in children with normal intelligence Attention deficit
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 447
fatigability and visualndashspatial construction dysfunctioncan result in specific learning disorders with impair-ment in reading and spelling as well as in mathematics
Psychosocial management Healthcare professionals have a responsibility to co-
ordinate specialist care and support services for childrenwith DM1 There is a need to be alert to the psychologicaland social dysfunctions and monitor home and educa-tional circumstances Liaison between agencies is essentialto ensure a consistent approach between health educationand social care agencies
Children with DM1 should have access to appropriatepsychological and therapy services at an early age to ensurethey are fulfilling their maximum potential and learningcoping strategies for later life The modification of activitiesincluding social engagement strategies would providea foundation for each child to grow in confidence and esteem
Family care and support is essential throughout child-hood with support and social care assistance whererequired Schools should be provided with specialistinformation about the care and management of a childwith DM1 A social work consult or a referral to nursingcase management can also be beneficial for patients Aholistic approach is critical because the affected parentmay also need additional assistance
Families should have access to disability benefitsadequate housing and adaptations during the progressionof the condition
Excessive daytime sleepiness Family members and educators should be educated about
the EDS that comes with DM1 Children should be screened for signs of EDS including
prolonged naps or falling asleep in school Possible sleep apnea should be evaluated with overnight
oximetry or polysomnogram Positive-pressure ventilation can be considered if a DM1
patientrsquos sleepiness is thought to be related to nocturnalor daytime hypoventilation or sleep apnea Patientsshould be referred to pulmonologists who have experi-ence in neuromuscular diseases for consideration ofassisted ventilation
Stimulant therapy with a psychostimulant such asmodafinil (Provigil) methylphenidate or other stimulantcan be considered if central hypersomnia is suspectedOften difficulty staying awake in school is a triggeringfactor Special care should be taken in children withpreviously detected cardiac arrhythmia (See Cardiacsection on stimulant management)
Endocrine and metabolismc DM1 male patients should undergo a detailed physical
examination in search of gonadal atrophy or cryptorchidismc Patients should have a HbA1c and thyroid-stimulating
hormone and Free T4 level measured at baseline andevery 3 years or if there is a clinical suspicion
c Adolescent patients should be screened as adult patients Gonadal insufficiency and complications of the
reproductive system Inquiring about amenorrheaor dysmenorrhea for the female patients and erectiledysfunction for male patients
Fasting blood lipids plasma glucose liver enzymesbilirubin levels and gamma-glutamyl transpeptidaseshould be measured at baseline
ConclusionsThe recommendations for care of congenital and childhood-onset myotonic dystrophy have been created by consensus ofclinicians experienced in their care management Given theabsence of rigorous studies in many of these areas theseguidelines were created by consensus They are designed tostandardize the care of children with a multisystemic disorderthat leads to significant morbidity and mortality
Study fundingMyotonic Dystrophy Foundation
DisclosureN Johnson serves on the scientific advisory boards ofCytokinetics AveXis AMO Pharma and Biogen Idec hasreceived funding for travel andor speaker honoraria fromStrongbridge serves as a consultant for AMO PharmaAveXis and Vertex Pharma and receives research supportfrom Ionis Pharmaceuticals Biogen Idec Valerion Thera-peutics Cytokinetics Acceleron AveXis AMO PharmaNIHNINDS FDA Muscular Dystrophy Association andMyotonic Dystrophy Foundation EZ Aldana and NAngeard report no disclosures T Ashizawa serves on sci-entific advisory boards for the Myotonic Dystrophy Foun-dation NIH and National Ataxia Foundation has receivedfunding for travel from Biohaven PacBio and NIHreceives research support from Myotonic DystrophyFoundation National Ataxia Foundation Biohaven Phar-maceuticals Biogen andNIHNINDS and is a professor atWeill Cornell Medical College adjunct professor at BaylorCollege of Medicine guest faculty at Central South Uni-versity China KN Berggren serves on the scientific advi-sory board of Biogen and receives funding for travel andorspeaker honoraria from HDSA and FSH Society C Marini-Bettolo has served on the scientific advisory boards ofAvexis and Biogen T Duong A-B Ekstrom V Sansone CTian and L Hellerstein report no disclosures C Campbellserves on the scientific advisory boards of Catabasis andPTC Therapeutics and receives research support fromValerion Pharmaceuticals PTC Therapeutics Pfizer IonisEli Lilly Prosensa Child Health Foundation and JessersquosJourney Foundation Full disclosure form informationprovided by the authors is available with the full text of thisarticle at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 21 2018 Accepted infinal form March 4 2019
448 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
Appendix Authors
Name Location Role Contribution
Nicholas EJohnson MDMCSI
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscriptpublication of thedraft and revision
EugenioZapataAldana MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NathalieAngeard PhD
Inserm ampUniversity of ParisDescartes ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
TetsuoAshizawa MD
HoustonMethodistNeurologicalInstitute Texas
Author Data acquisitiondrafting andrevision of themanuscript
Kiera NBerggren MACCC-SLP MS
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscript
Chiara Marini-Bettolo MDPhD
Institute of GeneticMedicineNewcastleUniversity andNewcastle uponTyne HospitalsNHS FoundationTrust Newcastleupon Tyne UK
Author Data acquisitiondrafting andrevision of themanuscript
Appendix (continued)
Name Location Role Contribution
Tina DuongMPT PhD
StanfordUniversity CA
Author Data acquisitiondrafting andrevision of themanuscript
Anne-BeritEkstrom MDPhD
Queen SilviaChildrenrsquo sHospitalGothenburgSweden
Author Data acquisitiondrafting andrevision of themanuscript
ValeriaSansone MD
NEMO ClinicMilan Italy
Author Data acquisitiondrafting andrevision of themanuscript
Cuixia TianMD
CincinnatiChildrenrsquos HospitalMedical CenterCincinnati OH
Author Data acquisitiondrafting andrevision of themanuscript
LeahHellersteinLCSW MPH
MyotonicDystrophyFoundation SanFrancisco CA
CorrespondingAuthor
Obtaining fundingdrafting andreviewing themanuscript studyconcept anddesign
CraigCampbell MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 449
450 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 451
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
impairment or profound irritable bowel symptoms aresigns often related to myotonia
c Mexiletine (Mexitil) is an option for myotonia if it isdemonstrated and is distressing to the patient Mexiletinemay not be approved for use in every country In these casesother sodium channel antagonists may be considered Because mexiletine is an antiarrhythmic an ECG
before use again within 3 months of starting therapyand then at serial intervals is recommended
Instruct the patient to avoid dyspepsia and transientldquodizzy feelingsrdquo associated with mexiletine treatmentby taking it with food to extend absorption and lowerpeak level in blood
Ocular and hearing management Baseline audiometry should be performed especially at
school age Ophthalmologic assessment should be performed at
diagnosis and at least yearly to evaluate for hyperopiastigmatism strabismus and visual acuity to preventevolution of visual impairment
Eyelid ptosis if ptosis becomes severe and interferes withvision intervention such as eyelid ldquocrutchesrdquo that can beinserted into glasses may be warranted Try crutches asa remedy for ptosis before eyelid surgery is consideredbecause of anesthesia risks Ophthalmic lubricants for dryeye may be considered
Gastrointestinal andgenitourinary management
c Presence of gastrointestinal symptoms such as abdom-inal pain constipation fecal incontinence or diarrheamay be a frequent problem The symptoms may mimicirritable bowel syndrome (IBS)15 Fiber supplementa-tion (more than 8 g daily) is the first-line treatment
c Gentle laxatives (see below) for constipation Oilsshould be avoided as they will lead to diarrhea Ifa patient does not respond to the first- or second-linerecommendations below a referral to a gastrointestinalspecialist for anal manometry should be considered First-line therapy recommendations polyethylene
glycol (Miralax) senna (Ex-Lax Senokot) docusate(Colace) or lactulose (Cholac)
Second-line therapy recommendations bisacodyl(Dulcolax Correctol) lubiprostone (Amitiza) orlinaclotide (Linzess)
Metoclopramide (Reglan) may be used to reduce thesymptoms of gastroparesis pseudo-obstruction andgastric reflux Providers should be aware of the risk ofacute dystonic reactions with this medication Long-term use is not recommended because this drug cancause tardive dyskinesia
Cholestyramine and loperamide are other options inthe presence of mainly diarrhea and anticholinergicdrug such as hyoscyamine sulfate in the presence ofIBS Because anticholinergic drugs may be antiar-rhythmic see Cardiac section on management
Mexiletine may be considered for refractory diarrheaor constipation because the drug may be antiarrhyth-mic see Cardiac section on management
c If bacterial overgrowth is found on breath testingtreating with antibiotics may reduce diarrhea
Focus on CDM As mentioned in the neonatal care section children with
CDMmay require a temporary feeding tube If dysphagiapersists consider enteral nutrition Refer to speech therapyChildren should be periodically re-assessed for improvingdysphagia
Children with CDMoften benefit from dysphagia therapyWith aggressive dysphagia therapy children with CDMoften are able to feed orally within the first year of life
Neurodevelopmental managementRecommendations
c Neuropsychological testing should be performed inevery child with DM1 to delineate cognitive strengthsand weaknesses This may include the following Psychometric assessment of global intellectual abilityand adaptive functioning
Assessment of executive functions Assessment of social cognition Assessment of visuomotor integration and visuospatialability
Assessment of receptive and expressive language abilities Assessment of EDS Assessment of learning disabilities (specific tests fordyscalculia dyslexia and dyspraxia)
c The assessments should be performed in the congenitalform in preschool age and should be repeated depend-ing on the level of functioning 2ndash3 times beforeadulthood In childhood DM1 neuropsychologicaltesting is recommended at diagnosis and repeated inpreschool or school age and college period
c Patients with psychiatric or behavioral issues should bereferred to a mental health care professional forassessment of Autism Spectrum Disorders AttentionDeficit disorders with or without Hyperactivity alex-iythmia and other behavioral problems
c Psychostimulants may be beneficial if attention deficitsare associated with an impairing level of fatigue or EDS(see excessive daytime sleepiness) As psychostimulantsmay be proarrhythmic see Cardiac section on stimulantmanagementSerotonin-enhancing antidepressants if excessive anxietyor other treatable psychiatric symptoms are present
Specific cognitive remediation programs to enhance socialemotional abilities (visual contact joint attention emotionalregulation) or executive functions efficiency (inhibitorycontrol attention working memory and cognitive flexibil-ity) using dedicated software (eg Cogmedreg)
c Language remediation and reading therapy should beconsidered because of the presence of cognitive deficitseven in children with normal intelligence Attention deficit
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 447
fatigability and visualndashspatial construction dysfunctioncan result in specific learning disorders with impair-ment in reading and spelling as well as in mathematics
Psychosocial management Healthcare professionals have a responsibility to co-
ordinate specialist care and support services for childrenwith DM1 There is a need to be alert to the psychologicaland social dysfunctions and monitor home and educa-tional circumstances Liaison between agencies is essentialto ensure a consistent approach between health educationand social care agencies
Children with DM1 should have access to appropriatepsychological and therapy services at an early age to ensurethey are fulfilling their maximum potential and learningcoping strategies for later life The modification of activitiesincluding social engagement strategies would providea foundation for each child to grow in confidence and esteem
Family care and support is essential throughout child-hood with support and social care assistance whererequired Schools should be provided with specialistinformation about the care and management of a childwith DM1 A social work consult or a referral to nursingcase management can also be beneficial for patients Aholistic approach is critical because the affected parentmay also need additional assistance
Families should have access to disability benefitsadequate housing and adaptations during the progressionof the condition
Excessive daytime sleepiness Family members and educators should be educated about
the EDS that comes with DM1 Children should be screened for signs of EDS including
prolonged naps or falling asleep in school Possible sleep apnea should be evaluated with overnight
oximetry or polysomnogram Positive-pressure ventilation can be considered if a DM1
patientrsquos sleepiness is thought to be related to nocturnalor daytime hypoventilation or sleep apnea Patientsshould be referred to pulmonologists who have experi-ence in neuromuscular diseases for consideration ofassisted ventilation
Stimulant therapy with a psychostimulant such asmodafinil (Provigil) methylphenidate or other stimulantcan be considered if central hypersomnia is suspectedOften difficulty staying awake in school is a triggeringfactor Special care should be taken in children withpreviously detected cardiac arrhythmia (See Cardiacsection on stimulant management)
Endocrine and metabolismc DM1 male patients should undergo a detailed physical
examination in search of gonadal atrophy or cryptorchidismc Patients should have a HbA1c and thyroid-stimulating
hormone and Free T4 level measured at baseline andevery 3 years or if there is a clinical suspicion
c Adolescent patients should be screened as adult patients Gonadal insufficiency and complications of the
reproductive system Inquiring about amenorrheaor dysmenorrhea for the female patients and erectiledysfunction for male patients
Fasting blood lipids plasma glucose liver enzymesbilirubin levels and gamma-glutamyl transpeptidaseshould be measured at baseline
ConclusionsThe recommendations for care of congenital and childhood-onset myotonic dystrophy have been created by consensus ofclinicians experienced in their care management Given theabsence of rigorous studies in many of these areas theseguidelines were created by consensus They are designed tostandardize the care of children with a multisystemic disorderthat leads to significant morbidity and mortality
Study fundingMyotonic Dystrophy Foundation
DisclosureN Johnson serves on the scientific advisory boards ofCytokinetics AveXis AMO Pharma and Biogen Idec hasreceived funding for travel andor speaker honoraria fromStrongbridge serves as a consultant for AMO PharmaAveXis and Vertex Pharma and receives research supportfrom Ionis Pharmaceuticals Biogen Idec Valerion Thera-peutics Cytokinetics Acceleron AveXis AMO PharmaNIHNINDS FDA Muscular Dystrophy Association andMyotonic Dystrophy Foundation EZ Aldana and NAngeard report no disclosures T Ashizawa serves on sci-entific advisory boards for the Myotonic Dystrophy Foun-dation NIH and National Ataxia Foundation has receivedfunding for travel from Biohaven PacBio and NIHreceives research support from Myotonic DystrophyFoundation National Ataxia Foundation Biohaven Phar-maceuticals Biogen andNIHNINDS and is a professor atWeill Cornell Medical College adjunct professor at BaylorCollege of Medicine guest faculty at Central South Uni-versity China KN Berggren serves on the scientific advi-sory board of Biogen and receives funding for travel andorspeaker honoraria from HDSA and FSH Society C Marini-Bettolo has served on the scientific advisory boards ofAvexis and Biogen T Duong A-B Ekstrom V Sansone CTian and L Hellerstein report no disclosures C Campbellserves on the scientific advisory boards of Catabasis andPTC Therapeutics and receives research support fromValerion Pharmaceuticals PTC Therapeutics Pfizer IonisEli Lilly Prosensa Child Health Foundation and JessersquosJourney Foundation Full disclosure form informationprovided by the authors is available with the full text of thisarticle at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 21 2018 Accepted infinal form March 4 2019
448 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
Appendix Authors
Name Location Role Contribution
Nicholas EJohnson MDMCSI
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscriptpublication of thedraft and revision
EugenioZapataAldana MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NathalieAngeard PhD
Inserm ampUniversity of ParisDescartes ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
TetsuoAshizawa MD
HoustonMethodistNeurologicalInstitute Texas
Author Data acquisitiondrafting andrevision of themanuscript
Kiera NBerggren MACCC-SLP MS
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscript
Chiara Marini-Bettolo MDPhD
Institute of GeneticMedicineNewcastleUniversity andNewcastle uponTyne HospitalsNHS FoundationTrust Newcastleupon Tyne UK
Author Data acquisitiondrafting andrevision of themanuscript
Appendix (continued)
Name Location Role Contribution
Tina DuongMPT PhD
StanfordUniversity CA
Author Data acquisitiondrafting andrevision of themanuscript
Anne-BeritEkstrom MDPhD
Queen SilviaChildrenrsquo sHospitalGothenburgSweden
Author Data acquisitiondrafting andrevision of themanuscript
ValeriaSansone MD
NEMO ClinicMilan Italy
Author Data acquisitiondrafting andrevision of themanuscript
Cuixia TianMD
CincinnatiChildrenrsquos HospitalMedical CenterCincinnati OH
Author Data acquisitiondrafting andrevision of themanuscript
LeahHellersteinLCSW MPH
MyotonicDystrophyFoundation SanFrancisco CA
CorrespondingAuthor
Obtaining fundingdrafting andreviewing themanuscript studyconcept anddesign
CraigCampbell MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 449
450 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 451
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
fatigability and visualndashspatial construction dysfunctioncan result in specific learning disorders with impair-ment in reading and spelling as well as in mathematics
Psychosocial management Healthcare professionals have a responsibility to co-
ordinate specialist care and support services for childrenwith DM1 There is a need to be alert to the psychologicaland social dysfunctions and monitor home and educa-tional circumstances Liaison between agencies is essentialto ensure a consistent approach between health educationand social care agencies
Children with DM1 should have access to appropriatepsychological and therapy services at an early age to ensurethey are fulfilling their maximum potential and learningcoping strategies for later life The modification of activitiesincluding social engagement strategies would providea foundation for each child to grow in confidence and esteem
Family care and support is essential throughout child-hood with support and social care assistance whererequired Schools should be provided with specialistinformation about the care and management of a childwith DM1 A social work consult or a referral to nursingcase management can also be beneficial for patients Aholistic approach is critical because the affected parentmay also need additional assistance
Families should have access to disability benefitsadequate housing and adaptations during the progressionof the condition
Excessive daytime sleepiness Family members and educators should be educated about
the EDS that comes with DM1 Children should be screened for signs of EDS including
prolonged naps or falling asleep in school Possible sleep apnea should be evaluated with overnight
oximetry or polysomnogram Positive-pressure ventilation can be considered if a DM1
patientrsquos sleepiness is thought to be related to nocturnalor daytime hypoventilation or sleep apnea Patientsshould be referred to pulmonologists who have experi-ence in neuromuscular diseases for consideration ofassisted ventilation
Stimulant therapy with a psychostimulant such asmodafinil (Provigil) methylphenidate or other stimulantcan be considered if central hypersomnia is suspectedOften difficulty staying awake in school is a triggeringfactor Special care should be taken in children withpreviously detected cardiac arrhythmia (See Cardiacsection on stimulant management)
Endocrine and metabolismc DM1 male patients should undergo a detailed physical
examination in search of gonadal atrophy or cryptorchidismc Patients should have a HbA1c and thyroid-stimulating
hormone and Free T4 level measured at baseline andevery 3 years or if there is a clinical suspicion
c Adolescent patients should be screened as adult patients Gonadal insufficiency and complications of the
reproductive system Inquiring about amenorrheaor dysmenorrhea for the female patients and erectiledysfunction for male patients
Fasting blood lipids plasma glucose liver enzymesbilirubin levels and gamma-glutamyl transpeptidaseshould be measured at baseline
ConclusionsThe recommendations for care of congenital and childhood-onset myotonic dystrophy have been created by consensus ofclinicians experienced in their care management Given theabsence of rigorous studies in many of these areas theseguidelines were created by consensus They are designed tostandardize the care of children with a multisystemic disorderthat leads to significant morbidity and mortality
Study fundingMyotonic Dystrophy Foundation
DisclosureN Johnson serves on the scientific advisory boards ofCytokinetics AveXis AMO Pharma and Biogen Idec hasreceived funding for travel andor speaker honoraria fromStrongbridge serves as a consultant for AMO PharmaAveXis and Vertex Pharma and receives research supportfrom Ionis Pharmaceuticals Biogen Idec Valerion Thera-peutics Cytokinetics Acceleron AveXis AMO PharmaNIHNINDS FDA Muscular Dystrophy Association andMyotonic Dystrophy Foundation EZ Aldana and NAngeard report no disclosures T Ashizawa serves on sci-entific advisory boards for the Myotonic Dystrophy Foun-dation NIH and National Ataxia Foundation has receivedfunding for travel from Biohaven PacBio and NIHreceives research support from Myotonic DystrophyFoundation National Ataxia Foundation Biohaven Phar-maceuticals Biogen andNIHNINDS and is a professor atWeill Cornell Medical College adjunct professor at BaylorCollege of Medicine guest faculty at Central South Uni-versity China KN Berggren serves on the scientific advi-sory board of Biogen and receives funding for travel andorspeaker honoraria from HDSA and FSH Society C Marini-Bettolo has served on the scientific advisory boards ofAvexis and Biogen T Duong A-B Ekstrom V Sansone CTian and L Hellerstein report no disclosures C Campbellserves on the scientific advisory boards of Catabasis andPTC Therapeutics and receives research support fromValerion Pharmaceuticals PTC Therapeutics Pfizer IonisEli Lilly Prosensa Child Health Foundation and JessersquosJourney Foundation Full disclosure form informationprovided by the authors is available with the full text of thisarticle at Neurologyorgcp
Publication historyReceived byNeurology Clinical PracticeDecember 21 2018 Accepted infinal form March 4 2019
448 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
Appendix Authors
Name Location Role Contribution
Nicholas EJohnson MDMCSI
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscriptpublication of thedraft and revision
EugenioZapataAldana MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NathalieAngeard PhD
Inserm ampUniversity of ParisDescartes ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
TetsuoAshizawa MD
HoustonMethodistNeurologicalInstitute Texas
Author Data acquisitiondrafting andrevision of themanuscript
Kiera NBerggren MACCC-SLP MS
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscript
Chiara Marini-Bettolo MDPhD
Institute of GeneticMedicineNewcastleUniversity andNewcastle uponTyne HospitalsNHS FoundationTrust Newcastleupon Tyne UK
Author Data acquisitiondrafting andrevision of themanuscript
Appendix (continued)
Name Location Role Contribution
Tina DuongMPT PhD
StanfordUniversity CA
Author Data acquisitiondrafting andrevision of themanuscript
Anne-BeritEkstrom MDPhD
Queen SilviaChildrenrsquo sHospitalGothenburgSweden
Author Data acquisitiondrafting andrevision of themanuscript
ValeriaSansone MD
NEMO ClinicMilan Italy
Author Data acquisitiondrafting andrevision of themanuscript
Cuixia TianMD
CincinnatiChildrenrsquos HospitalMedical CenterCincinnati OH
Author Data acquisitiondrafting andrevision of themanuscript
LeahHellersteinLCSW MPH
MyotonicDystrophyFoundation SanFrancisco CA
CorrespondingAuthor
Obtaining fundingdrafting andreviewing themanuscript studyconcept anddesign
CraigCampbell MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 449
450 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 451
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
Appendix Authors
Name Location Role Contribution
Nicholas EJohnson MDMCSI
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscriptpublication of thedraft and revision
EugenioZapataAldana MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NathalieAngeard PhD
Inserm ampUniversity of ParisDescartes ParisFrance
Author Data acquisitiondrafting andrevision of themanuscript
TetsuoAshizawa MD
HoustonMethodistNeurologicalInstitute Texas
Author Data acquisitiondrafting andrevision of themanuscript
Kiera NBerggren MACCC-SLP MS
VirginiaCommonwealthUniversity Virginia
Author Data acquisitiondrafting andrevision of themanuscript
Chiara Marini-Bettolo MDPhD
Institute of GeneticMedicineNewcastleUniversity andNewcastle uponTyne HospitalsNHS FoundationTrust Newcastleupon Tyne UK
Author Data acquisitiondrafting andrevision of themanuscript
Appendix (continued)
Name Location Role Contribution
Tina DuongMPT PhD
StanfordUniversity CA
Author Data acquisitiondrafting andrevision of themanuscript
Anne-BeritEkstrom MDPhD
Queen SilviaChildrenrsquo sHospitalGothenburgSweden
Author Data acquisitiondrafting andrevision of themanuscript
ValeriaSansone MD
NEMO ClinicMilan Italy
Author Data acquisitiondrafting andrevision of themanuscript
Cuixia TianMD
CincinnatiChildrenrsquos HospitalMedical CenterCincinnati OH
Author Data acquisitiondrafting andrevision of themanuscript
LeahHellersteinLCSW MPH
MyotonicDystrophyFoundation SanFrancisco CA
CorrespondingAuthor
Obtaining fundingdrafting andreviewing themanuscript studyconcept anddesign
CraigCampbell MD
University ofWestern OntarioOntario Canada
Author Data acquisitiondrafting andrevision of themanuscript
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 449
450 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 451
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
450 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 451
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 451
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
452 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
NeurologyorgCP Neurology Clinical Practice | Volume 9 Number 5 | October 2019 453
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
References1 Fu YH Pizzuti A Fenwick RG Jr et al An unstable triplet repeat in a gene related to
myotonic muscular dystrophy Science 19922551256ndash12582 Brook JD McCurrach ME Harley HG et al Molecular basis of myotonic dystrophy
expansion of a trinucleotide (CTG) repeat at the 3rsquo end of a transcript encodinga protein kinase family member Cell 199268799ndash808
3 Mahadevan M Tsilfidis C Sabourin L et al Myotonic dystrophy mutation an unstableCTG repeat in the 3rsquo untranslated region of the gene Science 19922551253ndash1255
4 Harper PS Myotonic Dystrophy 3rd ed London WB Saunders 20015 Bugiardini E Meola G DM-CNS Group Consensus on cerebral involvement in
myotonic dystrophy Neuromuscul Disord 201424445ndash4526 Koch MC Grimm T Harley HG Harper PS Genetic risks for children of women
with myotonic dystrophy Am J Hum Genet 1991481084ndash10917 Gagnon C Heatwole C Hebert LJ et al Report of the third outcome measures in
myotonic dystrophy type 1 (OMMYD-3) international workshop Paris France June8 2015 J Neuromuscul Dis 20185523ndash537
8 Johnson NE Hung M Nasser E et al The impact of pregnancy on myotonic dys-trophy a registry-based study J Neuromuscul Dis 20152447ndash452
9 Campbell C Levin S Siu VM et al Congenital myotonic dystrophy Canadianpopulation-based surveillance study J Pediatr 2013163120ndash123
10 Campbell C Sherlock R Jacob P Blayney M Congenital myotonic dystrophyassisted ventilation duration and outcome Pediatrics 2004113811ndash816
11 Angeard N Gargiulo M Jacquette A et al Cognitive profile in childhood myotonicdystrophy type 1 is there a global impairment Neuromuscul Disord 200717451ndash458
12 Ekstrom AB Hakenas-Plate L Tulinius M Wentz E Cognition and adaptive skills inmyotonic dystrophy type 1 a study of 55 individuals with congenital and childhoodforms Dev Med Child Neurol 200951982ndash990
13 Kroksmark AK Ekstrom AB Bjorck E Tulinius M Myotonic dystrophy muscleinvolvement in relation to disease type and size of expanded CTG-repeat sequenceDev Med Child Neurol 200547478ndash485
14 Johnson NE Ekstrom AB Campbell C et al Parent-reported multi-national study ofthe impact of congenital and childhood onset myotonic dystrophy Dev Med ChildNeurol 201658698ndash705
15 Yao X Yang YS Cui LH et al Subtypes of irritable bowel syndrome on Rome IIIcriteria a multicenter study J Gastroenterol Hepatol 201227760ndash765
Share Your Insights Expertise and Experiencesbull How are you employing drugs and devices in your field
bull What ethical challenges do you face
bull Do you have a case report that is illustrative of a clinical challenge
bull What challenges have you faced or successes have you enjoyed in bringing greater efficiency to your practice
Deliver a high-quality peer-reviewed message to your colleagues in practice submit your paper at NPuborgNCPsubmit
454 Neurology Clinical Practice | Volume 9 Number 5 | October 2019 NeurologyorgCP
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract
DOI 101212CPJ000000000000064620199443-454 Published Online before print April 24 2019Neurol Clin Pract
Nicholas E Johnson Eugenio Zapata Aldana Nathalie Angeard et al dystrophy type 1
Consensus-based care recommendations for congenital and childhood-onset myotonic
This information is current as of April 24 2019
ServicesUpdated Information amp
httpcpneurologyorgcontent95443fullhtmlincluding high resolution figures can be found at
References httpcpneurologyorgcontent95443fullhtmlref-list-1
This article cites 14 articles 3 of which you can access for free at
Citations httpcpneurologyorgcontent95443fullhtmlotherarticles
This article has been cited by 1 HighWire-hosted articles
Subspecialty Collections
httpcpneurologyorgcgicollectiondevelopmental_disordersDevelopmental disorders
httpcpneurologyorgcgicollectionall_pediatricAll Pediatric
httpcpneurologyorgcgicollectionall_neuromuscular_diseaseAll Neuromuscular Diseasefollowing collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpcpneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpcpneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
reserved Print ISSN 2163-0402 Online ISSN 2163-0933Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology All rightssince 2011 it is now a bimonthly with 6 issues per year Copyright Copyright copy 2019 The Author(s)
is an official journal of the American Academy of Neurology Published continuouslyNeurol Clin Pract