My Op at Hies

8/8/2019 My Op at Hies

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HEREDITARYMETABOLIC

ENDOCRINE ANDTOXIC


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DUCHENNE MUSCULAR DYSTROPHYBECKER MUSCULAR DYSTROPHY

MYOTONIC DYSTROPHYFACIOSCAPULOHUMERAL (FSH)MUSCULAR DYSTROPHY

LIMB-GIRDLE MUSCULAR DYSTROPHYOCULOPHARYNGEAL DYSTROPHYCONGENITAL MUSCULAR DYSTROPHYDISTAL MYOPATHIES


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Muscular dystrophy refers to a group of hereditary progressive diseases each withunique phenotypic and genetic features.


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X-l inked recessive disorder.Duchenne dystrophy is caused by a mutation of

the gene that encodes dystrophin, a 427-kDaprotein loca lized to the inner surface of the

sarco lemma of the musc le fiber.It is loca lized to the short arm of theX chromosome at Xp21The most common gene mutation is a de letion.


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Disorder usua lly becomes apparent between ages 3

and 5.The boys fa ll frequent ly and have difficu lty keeping upwith friends when p laying.By age 5, musc le weakness is obvious by musc le

testingGowers sign-O n getting up from thef loor, the patient uses his hands to c limb up himse lf.Contractures of the hee l cords and i liotibia l bands

become apparent by age 6.

Clinical Features


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Toe wa lking is associated with a lordotic posture.Loss of musc le strength is progressive, with predi lection

for proxima l limb musc les and the neck f lexors.Leg invo lvement is more severe than arm invo lvement.By age 12, most patients are whee lchair dependent.Progressive sco liosis often deve lops the chest deformity

which impairs pu lmonary function.By age 16 to 18 , patients are predisposed to serious,

sometimes fata l pu lmonary infections .

Clinical Features


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O ther causes of death inc lude aspiration of food andacute gastric di lation.The typica l ECG shows an increase net RS in lead V1;deep, narrow Q waves in the precordia l leads; andta ll right precordia l R waves in V1.

Intellectua

limpairment in Duchenne dystrophy iscommon,

The average inte lligence quotient (IQ)is approximate lyone standard deviation be low the mean.

Clinical Features


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Serum creatine kinase (CK) leve ls are invariab lye levated to between 20 and 100 times norma l.The leve ls are abnorma l at birth but dec line late in the

disease because of inactivity and loss of musc le mass.Electromyography (EMG) demonstrates features

typicalof myopathy.The musc le biopsy shows musc le fibers of varying

size as we ll as sma ll groups of necrotic andregenerating fibers. Connective tissue and fat rep lacelost musc

le fibers.

Laboratory Features


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Glucocorticoids, administered as prednisone in a doseof 0.75 mg/kg/day , significant ly slow progression of Duchenne dystrophy for upto 3 years.

Treatment


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X-l inked recessive disorder.Becker & Keiner in 1955.

3/1,00,000.Clinical FeaturesResemb les that seen in Duchenne.Proxima l musc les, especia lly of the lower

extremities.Hypertrophy of musc les, particu lar ly in the ca lvesFirst experience difficu lties between ages 5 and

15 years, third or fourthdecade or even later a lso.


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Becker patients walk beyond age 15 un likeDMD s.

Most survive into the fourth or fifth decade.Cardiac invo lvement occurs in Beckerdystrophy and may resu lt in heart failure .

Laboratory Featureswestern b lot ana lysis of musc le biopsy areduced amount or abnorma l size of dystrophin.


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A utosoma l dominant.Mutation on chromosome 19 q13.3.

Clinical FeaturesW ide ly and invo lves many systems.

hatc hetfaced appearance due totempora lis, masseter, and facia l musc leatrophy and weakness.Fronta l ba ldness is characteristic of men withthe disease.


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N eck musc les -f lexors and sternoc leidomastoids ,and dista l limb musc les are invo lved ear ly.

Weakness of wrist extensors, fingerextensors, and intrinsic hand musc les impairs

function.A nkle dorsif lexor weakness causes footdrop .

Proxima l musc les remain strongerthroughout the course, a lthough preferentia l atrophy and weakness of quadriceps musc lesoccur in many patients.


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Pa lata l,pharyngea l, and tongue invo lvementproduce a dysarthric speech, nasa l voice, and

swa llowing prob lems.Some patientshave diaphragm andintercosta l musc le weakness, resu lting inrespiratory insufficiency.Myotonia, which usua lly appears by age5, isdemonstrab le by percussion of the thenareminence, the tongue, and wrist extensor

musc les.


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Myontoia causes a s low re laxation of handgrip after a forced vo luntary c losure.A dvanced musc le wasting makes myotoniamore difficu lt to detect.C ongenital myotonic dystrophy is a moresevere form and occurs in 25% of infants of affected mothers.Severe facia l and bu lbar weakness, transientneonata l respiratory insufficiency, and low IQ


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Laboratory FeaturesSe ldom requires lab studies as c linica l

diagnosis is good.Serum CK leve ls may be norma l or mi ldlye levated.Muscle biopsy - musc le atrophy, whichse lective ly involves type 1 fibers in 50% of cases.Typica lly, increased numbers of centra l nuc lei

can be seen.


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TreatmentPhenytoin is the preferred agent for the

occasiona l patient who requires anantimyotonia drug; other agents, particu lar lyquinine and procainamide, may worsencardiac conduction.Cardiac pacemaker insertion shou ld beconsidered for patients with unexp lainedsyncope or advanced conduction system


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Cardiac pacemaker insertion for patientswith unexp lained syncope or advanced

conduction system abnorma lities withevidence of second -degree heart b lock, ortrifascicu lar conduction disturbances withmarked pro longation of the PR interva l.Molded ank le -foot orthoses he lp preventfootdrop in patients with dista l lowerextremity weakness.


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.A utosoma l dominant.Dista l long arm of chromosome 4q35

1 in 20,000Clinical features

O nset in chi ldhood or young adu lthood.Facia l weakness is the initia l manifestation,appearing as an inabi lity to smi le, whist le, orfully close the eyes.Loss of scapu lar stabi lizers -scapu lar winging.


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Biceps and triceps musc les severe ly affected,with sparing of the de ltoid musc les.W eakness wrist extension > f lexion, andW eakness of the anterior compartmentmusc les of the legs may lead to foot drop.In 20% of patients, weakness progresses toinvolve the pe lvic girdle musc les, and possib lewhee lchair dependency may resu lt.O ther sys. invo lvement -HTN , nerve deafness.


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Laboratory Features .CKleve l may be norma l or mi ldly elevated.

EMG usually indicates a myopathic pattern.The musc le biopsy - nonspecific features of amyopathy. A prominent inf lammatoryinfiltrate, which is often mu ltifoca l indistribution, is present in some biopsysamp les.


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Treatment .N o specific treatment is avai lab le;

A nkle -foot orthoses are he lpfu l for footdrop.Scapu lar stabi lization procedures improvescapu lar winging but may not improvefunction.


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Both ma les & fema les.O nset from late in the first decade to the

fourth decade.A utosoma l dominant.Deficiency of dystrophin associatedglycoprotein( links it with extrace llularmatrix).


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Clinical featuresW eakness of prox. Leg mus. By 2 nd & 3rd

decade.Upper limb invo lvement with scapu larwinging.Respiratory invo lvement may rsu lt dueinvolvement of diaphragm , as maycardiomyopathy -- >arrhythmias.N orma l IQ.

Treatment N o specific treatment.


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This form of muscu lar dystrophyrepresentsone of severa l disorders

characterized by progressive externa l ophtha lmop legia, which consists of s low lyprogressive ptosis and limitation of eyemovements with sparing of pupi llaryreactions for light and accommodation.


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A utosoma l dominant.French & canadians are most ly involved.

Clinical featuresIt usua lly presents with ptosis and/ordysphagia in the fourth to sixth decade.Mild weakness of the neck and extremitiesa lso occurs.


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Laboratory featuresserum CK leve l may be 2 to 3O n biopsy, musc le fibers are found to containvacuo les, contain membranous whor ls,accumu lation of g lycogen, and othernonspecific debris re lated to lysosomes.A distinct feature of ocu lopharyngea ldystrophy is the presence of tubu larfilaments, 8.5 nm in diameter, in musc le ce ll

nuc lei.


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TreatmentCricopharyngea l myotomy may improve

swa llowing, a lthough it does not preventaspiration.Eyelid crutches can improve vision in patientsin whom ptosis.


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The dista l myopathies, are notab le for theirpreferentia l dista l distribution of musc le

weakness in contrast to most musc leconditions associated with proxima l weakness.


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W elander distal myopathy (AD) and tibial muscular dystrophy (AD) , are lateonset disorders, usua lly manifestingafter age 40.

N onanka distal myopathy (AR) andMiyoshi myopathy (AR)


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Disease Clinical Features Laboratory Features

W e lander dista lmyopathy

W eakness beginsin handsSlow progression

with spread todista l lowerextremitiesLifespan norma l

-Serum CK 2 3 xnorma l-EMG myopathic- N CS norma l-Muscle biopsyshows dystrophicfeatures


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Tibial Muscu lardystrophy(Markesbery/Griggs/Udd

-O nset 4th to 8thdecade-Dista l lowerextremity-weakness (tibia ldistribution)-Upper extremitiesusua lly norma l-Lifespan norma l

-Serum CK 2 4 xnorma l-EMG myopathic- N CS norma l-Muscle biopsyshows dystrophicFeatures- Titin absent in M -line of musc le


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N onanka dista lmyopathy(dista lmyopathywith rimmedvacuo les)

-O nset 2th to 3 rd

decade-Lower extremity dista lweakness-Mild dista l upper limbweakness may be

present ear ly-Progression to othermusc les sparingquadriceps-A mbu lation may belostin 10 15 years

-Serum CK 3 10norma l-EMG myopathic- N CS norma l-Dystrophic

features on musc lebiopsy p lus rimmedvacuo les15 19-nm filamentswithin vacuo les


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Miyoshimyopathy

-O nset 2d to 3d decade-Lower extremityweakness in posteriorcompartment musc les

-Progression leads to

weakness in othermusc le groups

- A mbu lation lost after10 15 years in aboutonethird of cases

-Serum CK 20 100norma l-EMG myopathic- N CS norma l-Muscle biopsy -

shows nonspecificdystrophic features


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CENTRAL CORE DISEASENEMALINE MYOPATHYCENTRONUCLEAR(MYOYUBULAR)MYOPATHY

MULTI CORE DISEASEFINGER PRINT BODY MYOPATHY

SARCOTUBULAR MYOPATHY

These rare disorders are distinguis hed from musculardystrop h ies by t he presence of specific h istoc hemical andstructural abnormalities in muscle.


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A DLong arm of chromosome 19.Patients with centra l core disease may havedecreased feta l movements and breechpresentation.Hypotonia and de lay in motor mi lestones,particu lar ly in walking, are common.Later in chi ldhood, patients deve lop prob lemswith stair c limbing, running, and getting up fromthe f loor.


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O n examination, there is mi ld facia l, neckf lexor, and proxima l- extremity musc le

weakness.Legs > arms.Ske leta l abnorma lities inc lude congenita l hipdislocation, sco liosis, and pes cavus; c lubbedfeet a lso occur.Most cases are nonprogressive.


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The serum CK leve l is usua lly norma l.Muscle biopsy shows fibers with sing le or

multip

le centra

lor eccentric discrete zones(cores) devoid of oxidative enzymes.

Treatment- Specific treatment is notrequired, but estab lishing a diagnosis of

centralcore disease is extreme

ly important,because these patients have a known

predisposition to ma lignant hyperthermiaduring anesthesia.

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