MUSCULAR DYSTROPHIES Muscular dystrophy is the largest and most common group of progressive neuromuscular disorders of childhood, although

signs of muscular dystrophy can occur at any point in the life span. It has a genetic origin and is characterized by ongoing symmetrical muscle wasting without neural or sensory deficits but with increasing deformity and disability. Paradoxically, the wasted muscle tend to hypertrophy because of connective tissue and fat deposits, giving the visual appearance of muscle strength. DYSTROPHIES : Hereditary or congenital disorder with progressive degeneration and muscle wasting. Pathogenesis of this disorder is unknown. lassification ! ". #$linked recessive female carry the abnormal gene which is located at the short arm of the x chromosome. %egative family history. &xamples! 'uchenne, (ecker, &mery$'reifus ). *utosomal dominant 'efect is seen in every generation of those affected. Positive family history. +. *utosomal recessive *ffected gene is non$dominant. ,ne of the parents carry the abnormal recessive gene but does not manifest the disease. %egative family history. -. #$linked dominant 'efective gene is x$chromosome. Postive family history.

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TYPE Duchenne MD Pseudohypertrophi c MD

MODE OF INHERITANCE #$linked recessive .female carriers/

INCIDENCE/ EPIDEMIOLOGY "01,222 live M births

ONSET )$3 y0o

ETIOLOGY 'efective gene in the p)" region of the short arm of the x chromosome affects the 4uantity and 4uality of the protein dystrophin. 'ystrophin deficiency causes impairment 5 degeneration in 6ype II$( muscle fibers.

PATHOPHYSIOLOGY 'ystrophin absence disrupts controlled calcium release causing large entry of calcium inside the cell and thereby resulting to proteolysis 5 eventually cell death. 7ith chronic necrosis,mm. regeneration fails.

CLINICAL MANIFESTATIONS (5- !/"#: 7eak pelvic girdle muscles 7addling gait 8way back posture Positive 9ower:s sign Pseudohypertrophy in ;2< ($ !/"#: .$/ stair climbing0walking shoulder$girdle weakness (%-1& !/"#: walking0standing with brace scoliosis "st apparent .=/ writing0>* activities (1' !/"#: wheelchair$bound hand function difficult completely dependent *'? impaired respiratory function (1 -'& !/"#: chest infection and cardiac failure Proximal to distal weakness Pelvic girdle ."st/ then shoulder girdle Pseudohypertrophy! constant feature Aespiratory failure! rare *mbulant in )nd or +rd decade of life

CLINICAL COUR SE 8evere rapid progression

LIFE SPAN 8hort@ death at )nd decade@ survival rare beyond mid$ )2:s

1 CAUSE OF DEATH "st ! respiratory )nd ! cardiac

PROGNOSIS 7orst of the dystrophies

(ec)e* MD

#$linked recessive .female carriers/

"012,222 live M births

*dolescence0 adulthood

Mutation of xp)"

8tructurally abnormal dystrophin with a degree of normal function accounting for the relative mildness of this variant.

8low progression

32 y0o .mild/@ )2:s .severe/

ardiac failure

Aelatively good@ *mbulant in )nd or +rd decade

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TYPE E+e*!-D*e,-u. MD Humeroperoneal MD

MODE OF INHERITANCE #$linked recessive .female carriers/

INCIDENCE/ EPIDEMIOLOGY "0"22,222 live M births

ONSET hildhood to early teens

ETIOLOGY 9ene defect on x chromosome that codes for the protein, &merin.

PATHOPHYSIOLOGY

CLINICAL MANIFESTATIONS lassic triad! &arly contractures .elbow, *chilles tendon, postcervical tiptoe, e4uinus/ ardiac conduction defect 7eakness or atrophy! humeroperoneal distribution Hypotonia0proximal limb weakness 5 Boint contractures at birth .arthrogryposis/ >acial muscle weakness %8 involvement.some/! tonic$clonic seizures Microcephaly MaBor feature! 8capular winging 7eakness! )nd$+rd decade >acial muscles generally spared ?imb girdle weakness.pelvis/ E& internal rotation with ambulation *lso! cardiopulmonary difficulties

CLINICAL COU RSE 8low progression

LIFE SPAN 8urvival up to middle age

1 CAUSE OF DEATH

PROGNOSIS 8ome unable to walk when they reach adulthood due to amputation of peroneal muscles

C"n/en,012 MD

*utosomal recessive, *utosomal dominant

Males and females

*t birth

*bnormal expression of dystrophin associated proteins.>ukuyama type/

8low progression

Aespiratory insufficiency

Progression is slow. 8ome patients learn to walk. Half never achieve the ability to stand

L,+3-/,*42e MD

*utosomal recessive, #$ linked recessive

MC>

?ate childhood to middle age

9ene defects that had been linked to the development of the disorder! chromosomes ),1,"+,"1,"D

9ross changes are nonspecific 5 consists of an early replacement by fat 5 fibrous tissue making the muscle appear yellow0white. 6hese infiltrations give rise to the pseudohypertrophic appearance of certain muscles.

Progressive, varies

8horter@ severity! intermediate

ardiopulmonary complications

8low progression with long periods of plateau. 6heb earlier the onset, the more rapid the progression. Many are severely disabled within )2 years of onset.

)"TYPE F1c,".c15u2"hu+e*12 MD Dejerine-Landouzy MD MODE OF INHERITANCE *utosomal dominant INCIDENCE/ EPIDEMIOLOGY +$"20million malesCfemales ONSET hildhood to early adulthood ETIOLOGY Enknown@ abnormal gene has been localized on chromosome PATHOPHYSIOLOGY CLINICAL MANIFESTATIONS )nd decade! onset facial weakness at "1 ."st/ shoulder girdle weakness F biceps 5 triceps .=/ (ell:s sign@ face is smooth0unlined and pouting lips scapular winging.primary disability/ wrist drop cardiac involvement! rare >acial apperance is typical! frontal baldness myopathic face with ptosis hanging Baw muscle wasting at neck, shoulder girdle, 5 muscles of mastication. ptosis0dysphagia! -th$3th decade ."st/ dysphagia, facial 5 proximal limb weakness.later/ pupillary reaction is spared muscles "st affected! hands0lower legs handsIlegs decreased tendon reflexes at ankle sensory loss in some patients rare! proximal weakness CLINICAL COUR SE Progressive, varies

M!"0"n,c D!.0*"5h!

*utosomal dominant

+$10"22,222

hildhood to middle age

9ene flaw on chromosome "G for an enzyme named myotonin protein kinase

8low progression

Ocu2"5h1*!n/e12 MD

*utosomal dominant

>rench$ anadians coomonly affected group

&arly adulthood to middle age

8low progression

D,.012 MD

*utosomal dominant

*ffects both males and females@ high in 8weden@ Aarest of all muscular dystrophy

-2$32 y0o

7elander! chromosome )p"+

8low progression but not life threatening

FUNCTIONAL GRADES (MUSCULAR DYSTROPHY# * 6I,%8 8tarting arms at sides@ patient can abduct arm in full circle$ overhead ) F Aaise arms above haed by using elbow flexion or acessory muscles + F an:t raise hand above head but only )-2ml .;oz./ glass of water to mouth .or with both hands/ F Aaise hand to mouth but not an ;oz glass of water 1 F an:t raise hand to mouth but hold a pen or pick$up coins from table 3 F an:t raise hand to mouth and no useful hand function ?& 9A*'&8 * 6I,%8 1 7alks0 climbs stairs without assistance 2 7alks0 climbs stairs with aid of railing 3 7alks0 climbs stairs slowly with aid of railing F 7alks unassisted, rises from chair, can:t climb stairs 1 F 7alks unassisted, can:t rise from chair or climb stairs 3 F 7alks only with assistance or walks independently with ??( D F 7alks in ??(, re4uires assistance for balance ; F 8tands in ??(, unable to walk with assistance G F 7heelchair$borne "2 F (ed$bound GENERAL DIAGNOSTIC TESTS IN MUSCULAR DYSTROPHY "/ PH serum enzyme determination E& 9A*'&8 1

)"1 )/ +/ -/ 1/ "/ &M9 Muscle biosy & 9 Pulmonary function tests MANAGEMENT OF MUSCULAR DYSTROPHIES 'E H&%%&! .$/ ure Medications! steroids Pulmonary Insufficiency! Jentilation ontractures! (races, stretching, positioning, surgery 'ecreased mobility secondary to contractures! (races 5 surgery 8coliosis! 8urgery omplications .osteoporosis/! minimal immobilization ?oss of strength! &xercise, &8 ?oss of hand function! A,M, stretching, positioning, splint, assistive device, work simplification techni4ues Preventive measures (& H&A Medications! steroids (races 8tretching 8urgery 7eight training program &M&AK$'A&I>E88 (races worn at night A,M Positioning Pacemaker .critical form of treatment/ ,%9&%I6*? M' Medications for seizures ?IM($9IA'?& M' Jentilatory assistance Monitored strength training >*8 I,8 *PE?,HEM&A*? 8urgery ,rthosis MK,6,%I Medications as stabilizers! phonytoin, 4uinine ?& orthoses , E?,PH*AK%9&*? %96 'I86*? ,rthopedic devices to improve ambulation.

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