clinical aspect of dystrophinopathies

• duchenne muscular dystrophy o onset 3 to 5 yrs o clinical § weakness o distribution § proximal > distal § symmetric § legs & arms § most involved muscles: adductor magnus in legs § relatively spared muscles: gracilis & sartorius o course § reduced motor function by 2 to 3 years § steady decline in strength: after 6 to 11 years o gowers sign: standing up with the aid of hands pushing on knees o failure to walk: 9 - 13 years § muscle hypertrophy o especially calf o may be generalized o § musculoskeletal o contractures § especially ankles3 o scoliosis § onset: after loss of ambulation § may be reduced if walking & standing is prolonged to 17 to 18 years § other clinical features o cardiomyopathy: dilated especially > 15 years o mental retardation: mean iq ~ 88 o night blindness o gastrointestinal: rare § type: pseudo-obstruction gastric dilatation § upper gi tract § late in disease course § death o most common between 15 - 25 years o due to respiratory or cardiac failure o life prolonged by ~ 6 years to 25 years with respiratory support8 o life shortened by 2 years with cardiomyopathy o • becker muscular dystrophy o genotype: dystrophin mutations o clinical features of myopathy § onset > 7 yrs § weakness o proximal > distal symmetric legs & arms o may be especially prominent in quadriceps or hamstrings o slowly progressive o severity & onset age correlate with muscle dystrophin levels § calf pain on exercise § muscle hypertrophy: especially calves § failure to walk 16 - 80 years o systemic § joint contractures: ankles & other § cardiomyopathy: may occur before severe weakness § mental retardation o associated with deletion of dp140 transcription unit o serum ck § very high: 5,000 to 20,000 § lower levels with increasing age • dystrophinopathies: cardiomyopathy5 o general features § nosology: x-linked dilated cardiomyopathy § onset: commonly in teenage years § types: dilated cardiomyopathy > hypertrophic > conduction defects § probable pathophysiology: dystrophin deficiency o two clinical types § cardiomyopathy with becker or duchenne md syndromes: common o common mutations: deletions in exons 48-53 region (spectrin-like region) o clinical features § tachycardia: > 100 common even < 10 years of age § dilated cardiomyopathy: may develop after period of hypertrophy increased frequency with age § conduction system abnormalities: occasional patients § symptomatic: 57% by age 18 § progression: variable § weakness: typical becker or duchenne syndrome § may be associated with only: myalgias after exercise & high ck § selective cardiomyopathy minimal or mild weakness o cardiac muscle dystrophin o skeletal muscle dystrophin o clinical features § weakness: minimal or mild § cardiomyopathy: males o onset: late teens o congestive heart failure o rapidly progressive: 1 to 2 years § cardiomyopathy: manifesting females o onset: 5th decade o congestive heart failure o chest pain: atypical o slowly progressive over > 10 years • dystrophinopathies: manifesting female carriers o weakness § course: progressive mild to severe onset 16 to 48 years § distribution o proximal & asymmetric o often arms > legs o shoulder abduction elbow flexion knee extension § female duchenne phenotype (rare) o severe weakness o muscle biopsy: absent dystrophin o normal x chromosome o total inactivation o usually associated with chromosomal translocation o cramps & myalgia: 70% have weakness o cardiomyopathy § dilated: duchenne 8% becker • mental retardation (several types) o reduced verbal iq § present in most dmd patients o reduced total iq < 80 o