Rett Syndrome

Alisha Byus · Renee Devlin · Anne Hoffman · Andrea Ruwe

History and Origin• Named for Dr. Andreas Rett,

organized in 1983• Vienna, Austria• Pediatrics and Neurology

• Observed 2 girls in waiting room with similar hand movements in 1960

• Initial symptoms indicate what neurons are affected in the brain

• First published article (Hasberg et al.) with additional cases in 1983

www.rettsyndrome.org

Pervasive Developmental Disorders

• Autistic Disorder• Asperger Disorder • Childhood Disintegrative Disorder • Rett Syndrome • Pervasive Developmental Disorder

- Not Otherwise Specified (PDD-NOS) Diagnostic Statistic Manual-4th Edition (1994): (DSM-IV)

→ As more is learned about Rett Syndrome, it is likely that the diagnostic criteria will soon be revised, and Rett syndrome will not be categorized with other pervasive developmental disorders. The characteristics of a child with Rett Syndrome are no longer congruent with those of a child with Autism.

Dr. Ratlif-Schaubb (2008) Nationwide Children’s Hospital

Etiology

• The majority of cases of Rett syndrome are caused by nonhereditary, acquired changes or mutations in the Rett syndrome gene on the X chromosome.

• Males with this defect often die before birth or in infancy• Males that live through infancy have an extra

X-chromosome in many/all of the body’s cells• Klinefelter syndrome

Etiology• Mutations in the CDKL5 and

MECP2 genes cause Rett syndrome • Majority of classic on the

MECP2 gene (75%)• This gene provides

direction for typical brain development.

• Connects synapses to nerve fibers

• Mutations in CDKL5:• Atypical form of Rett

syndrome• Early onset seizure

variant

Etiology: Inheritance

• 99% with classic Rett syndrome have no family history

• Inheritance research has shown:• X-linked• Dominant

• Groups with diseases in families more prevalent in:• Norway, Sweden,

Northern Italy• Genetics tests are used

but cannot identify every patient

Risk Factors

• There are no known risk factors with the exception of being female

• Mutation is sporadic

• Chance of having a second child with Rett Syndrome is less than 1%

• No opportunities for prevention

Other CommonMedical Issues

• Scoliosis: • 80% of girls with Rett Syndrome

• Constipation and gastro-esophageal reflux • Cardiac problems• Feeding, swallowing, chewing• Unusual breathing pattern (non-apneaic)• Sleep disruption

• Including sudden death in sleep• Seizures• Very little is known of the life expectancy

• Very few women in 40s/50s with diagnosis

Epidemiology

• Data are limited to case studies

• This disorder has been reported mainly in females

• Prevalence rate of Rett Syndrome:• 1 in 10,000 – 1 in

15,000

EpidemiologyRett Syndrome Course:

• Rett Syndrome has its onset prior to age 4 years, usually in the first or second year of life.

• The duration of the disorder is lifelong, and the loss of skills is generally persistent and progressive.

• In most instances, recovery is quite limited, although some very modest developmental gains may be made and interest in social interaction may be observed as individuals enter later childhood or adolescence.

• This disorder follows a continuous course. The social, communicative, and behavioral difficulties remain relatively constant throughout life.

Diagnostic FeaturesEssential features of Rett

Syndrome:

• Development of multiple specific deficits following a period of normal functioning after birth

• Apparently normal prenatal and perinatal period with normal psychomotor development through the first 5 months of life

• Head circumference at birth is also within normal limits

Epidemiology: Associated Features

• Typically associated with Severe or Profound Mental Retardation

• Increased frequency of EEG abnormalities and seizure disorder

• Nonspecific abnormalities on brain imaging have been reported

Differential Diagnosis• Rett syndrome is often

mistaken for autism, cerebral palsy, and mental retardation

• Rett syndrome differs from ChildhoodDisintegrative Disorder, Autistic Disorder &Asperger Syndrome in the following areas:

1. Sex ratio

2. Onset

3. Pattern of deficits

Diagnostic criteria for Rett Syndrome (DSM-IV)A. All of the following:

• apparently normal prenatal and perinatal development

• apparently normal psychomotor development through the first 5 months after birth

• normal head circumference at birth

B. Onset of all of the following after the period of normal development:

• deceleration of head growth between ages 5 and 48 months

• loss of previously acquired purposeful hand skills between ages 5 and 30 months with the subsequent development of stereotyped hand movements (e.g., hand-wringing or hand washing)

• loss of social engagement early in the course (although often social interaction develops later)

• appearance of poorly coordinated gait or trunk movements

• severely impaired expressive and receptive language development with severe psychomotor retardation

Diagnostic Criteria: StagesStage 1: 6-18 months

• Delayed head/brain growth

• Poor muscle tone

• Decreased interest in play/environment

Diagnostic Criteria: StagesStage 2: 12-36 months

• Language regressions

• Social skill regressions

• Motor skill regressions

• Social vacancy & stereotyped behaviors emerge

• Stereotypical ‘hand-wringing’ behavior not always evident. May present as hand-to-mouth or similar motor activity.

• May become irritable

Diagnostic Criteria: StagesStage 3

Stage 3: 2-10 years

• Social vacancy decreases

• Profound motor delays

Diagnostic Criteria: StagesStage 4

Stage 4: (10yrs+)

• Improved social interactive behaviors

• Processing speed issues

• Increased motor problems

• Oral-motor skills decrease• Often receive feeding tube at this

point if one is not already in place

“We have to be careful not to underestimate their capabilities. Often their motor limitations interfere with their abilities.”

Ex: ability to use sign language

Dr. Ratlif-Schaubb (2008) Nationwide Children’s Hospital

Services

• In recent years, advances in medical technology have led to increases in the survival of individuals with complex medical conditions

• This causes increasing numbers of children with disabilities, and increasing demands for services• Moore et al (2005)

Services

General trends for medical service use:

• Specialist appointments are most frequent in the younger age groups, and decline with age

• General practitioner appointments are frequent in younger age groups and increase with age

• Predisposing factors (e.g., demographics, social structure, genetics) played a large role in service use

• Moore et al (2005)

Services

Medical Services• Seizures

• Anti-seizure medications

• Feeding Disorders• GERD

• Behavioral issues/agitation/sleep disorders

Services

Physical Therapy• Usually begin when there is loss of

developmental milestones• Range of motion and ambulation

• Deformities and contractures• Maintaining postural alignment

• Loss of mobility• Range of motion, transferring, positioning

ServicesOccupational Therapy

• Increase the use of the body, especially hands• 75% of those with Rett Syndrome lose most

functional use of hands• Decrease repetitive hand movements• Feeding skills• Sensory processing• Encouraging independence

• A lot of the motor skill regressions can be prevented with aggressive OT. Working to decrease repetitive hand movements (ie. splits on hands) and improve functional hand use could prevent a total loss of motor ability.

Dr. Ratlif-Schaubb (2008)

Nationwide Children’s Hospital

Services

Nutrition• Seizure management

• Ketogenic diet

• Osteoporosis• Supplements

• Constipation

Services

Speech Therapy• Language development affected by

• General cognitive deficits, auditory processing, apraxia, dyarthria, abnormal respiration

• Expressive vs. receptive language abilities• Increase communication abilities

• Speech of augmentative communication

• Increase socialization/participation

Services

• Other potential therapies…• Hydrotherapy• Music Therapy• Hippotherapy

• International Rett Syndrome Association & Budden (1997)

Resources• Rett Syndrome Research Foundation (RSRF)

• Founded in 1999 by a group of parents concerned about the lack of research on Rett Syndrome

• the world's leading private funder of Rett research.• In the last five years RSRF has funded 104 projects at

premiere institutions totaling over $11 million• organizes the only annual scientific meeting devoted to

Rett Syndrome.• Each June RSRF convenes over 100 researchers and

clinicians from around the world for a three day Rett Syndrome symposium

• RSRF Office4600 Devitt DriveCincinnati, OH 45246Tel: (513) 874-3020http://www.rsrf.org/about_rsrf/

Resources• International Rett

Syndrome Association

• Stated purpose:• “to bring about cures

and treatments for Rett syndrome AS SOON AS POSSIBLE while taking care of the families and individuals living with Rett syndrome RIGHT NOW.”

• Information, research, family support, awareness, advocacy, fundraising

http://www.rettsyndrome.org/index.asp

Resources• Ohio’s Parent Guide to Autism

Spectrum Disorders• Developed by the Ohio Center for Autism and Low Incidence

(OCALI) Parent Resource Manual Task Force (including Pat Cloppert, Parent Advocate at the Nisonger Center)

• “This guide was developed and written by parents of individuals with autism spectrum disorders. The examples provided are from their experiences. The information included in this manual is a result of their answer to the question:

When your child was first diagnosed, what information did you need most?”

• http://www.ocali.org/family/fs_res_guide.php

Resources•Girl Power 2 Cure, Inc.

• “Girl power 2 Cure, Inc is a non-profit organization dedicated to raising funds for research for treatments and to find a cure for Rett Syndrome. The Foundation will also allocate funds to build and manage an interactive website where girls can learn about Rett Syndrome, and Rett families can find unique resources for their girls”

• Activities• Events/Programs• CD available for purchase

• proceeds benefit Rett research

• http://www.girlpower2cure.org/

Resources• Rett Angels

• Membership based• A collection of links,

current events and news items, blogs, pictures and personal stories.

• http://www.rettangels.org/news.php

Resources• The Blue Bird Circle Rett Center at Baylor

College of Medicine• One of just a few centers in the United State that specializes

in Rett Syndrome• Provides care to women and girls with Rett Syndrome

worldwide• Rett syndrome information package available upon request• Contact Information:

• 6621 Fannin Street, CC1250Houston,TX 77030Phone: 832-822-RETT (7388)Toll-free: 1-888-430-7388 Fax: 832-825-7388email: rett@bcm.edu

• http://www.bcm.edu/pediatrics/index.cfm?Realm=99991118&This_Template=pedi_home.cfm

Bibliography• Budden, S. (1997). Rett syndrome: Habilitation and management

reviewed. European Child & Adolescent Psychiatry, 6, 103-107.• This article examines the different services available to individuals

with Rett Syndrome, with emphasis on the areas of medical, nutritional, physical, and speech-language. Each of these areas is then subdivided into its different foci (e.g., medical deals with seizures, GERD, and agitation/behavioral disturbances). Each of the remediation techniques/methods discussed has been shown via research to be effective in the management of some aspect of the disorder. Additionally, the article mentions several additional therapies that may be helpful to some individuals (e.g., hippotherapy, hydrotherapy, music therapy). While slightly outdated, this is one of the few articles that provides a comprehensive overview of different methods to remediate some of the characteristics of the disorder.

Bibliography• Matson, J. (2007). Current status of differential diagnosis for

children with autism spectrum disorders. Research in Developmental Disabilities, 28, 109-118.• This article provides an overview of recent developments

regarding diagnosis of children with autism spectrum disorders, with emphasis on diagnosis in early childhood. The author describes common instruments used by clinicians for diagnosing on the autism spectrum (e.g. CARS, AID-R). Methods currently used for early (birth - 4 years) diagnosis are discussed (genetic mapping, screening questionnaires) are discussed. The article concludes with a review of the range of autism spectrum disorders (Aspergers Syndrome, Rett Syndrome), with particular attention to prevalence rates and diagnostic measures used to assess these disorders on the autism spectrum.

Bibliography• Moore, H., Leonard, H., de Klerk, N., Robertson, I., Fyfe, S.,

Christodoulou, J., Weaving, L., Davis, M., Mulroy, S., Colvin, L. (2004) Health service use in Rett syndrome. Journal of Child Neurology, 19, 42-50.• This article examines the extent to which different factors affect

service use by families with children who have Rett Syndrome. These factors include the following: age, maternal education, phenotype classification (mild atypical, classic, atypical early onset), X-inactivation, mutation location, and mutation type. The researchers then examined use of the following forms of medical service: annual rates of medical appointments, number of general practitioner appointments, number of specialist appointments, and annual rates of hospital admissions. Based on a multivariate analysis, it was determined that phenotype classification, maternal education, and X-inactivation were significant predictors of the use of medical services.

Bibliography• Morrison, J. & Anders, T. (1999). Interviewing children and adolescents:

Skills and strategies for effective DSM-IV diagnosis. New York: Guilford Press. 

• This book is designed for clinicians assessing children and adolescents. Psychiatric disorders typically diagnosed in non-adult populations, as outlined in the Diagnostic Statistical Manual (DSM) are described at length. The book contains an entire chapter on autism spectrum disorders, including diagnostic features and diagnostic criteria. This chapter is particularly helpful in differential diagnostics (e.g. differentiating Rett Syndrome from Childhood Disintegrative Disorder). The chapter also contains several case study vignettes which provide a more comprehensive illustration of disorders on the autism spectrum. These vignettes, in addition to a chapter that offers specific strategies for working with youth make this book an essential complement to the DSM.

Bibliography• Normura, Y and Segawa, M. (2005). Natural history of Rett syndrome.

Journal of Child Neurology. Vol. 20 (9), pp. 764-8.

• This article gave an historical look at the discovery and research behind Rett syndrome. It details the typical signs and symptoms present during onset, late infancy, early childhood, childhood, and adulthood. It also gives interesting data on a sleep study of patients diagnosed with Rett syndrome and associated disorders that have been found in these patients. It linked characteristic sleep abnormalities with gene components.

Bibliography• Therapies. (2007). International Rett Syndrome

Association. Retrieved November 16, 2007 from http://www.rettsyndrome.org/

• Harris, S., Glasberg, B., & Rice, D. (1996). Pervasive Developmental Disorders: Distinguishing among subtypes. The School Psychology Review, 25(3), 308-315.