Duchenne Muscular Dystrophy
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Duchenne Muscular Dystrophy Becker Muscular Dystrophy US Prevalence 15,000 2,200 Incidence Rate 1/3,500 male births Unknown Inheritance X-linked X-linked Gene location Xp21 (reading frame shifted) Xp21 (reading frame maintained) Protein Dystrophin Dystrophin Onset 2- 6 years 4-12 years (severe EMD) Late teenage to adulthood (mild EMD) Severity and course Relentlessly progressive Reduced motor function by 2-3 years Steady decline in strength Life span <35 years Slowly progressive Severity and onset correlate with muscle dystrophin levels Ambulation status Loss of ambulation 7 to 13 yrs (no corticosteroids) Loss of ambulation 9 to 15 years (corticosteroids) Loss of ambulation >16 years Weakness Proximal > distal Symmetric Legs and arms Proximal > distal Symmetric Legs and arms Cardiac Dilated cardiomyopathy first to second decade Onset of signs second decade Cardiomyopathy may occur before weakness, Third to fourth decade frequent Respiratory Profoundly reduced vital capacity in second decade Ventilatory dependency in second decade Respiratory involvement in subset of patients Ventilator dependency in severe patients Muscle size Calf hypertrophy Calf hypertrophy Musculoskeleta l Contractures: ankles, hips, and knees Scoliosis: onset after loss of ambulation Contractures: ankles and others in adulthood CNS Reduced cognitive ability or reduced verbal ability Some patients have reduced cognitive ability Muscle Endomysial fibrosis and Variable fiber size
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Transcript of Duchenne Muscular Dystrophy
Duchenne Muscular DystrophyBecker Muscular Dystrophy
US Prevalence15,0002,200
Incidence Rate1/3,500 male birthsUnknown
InheritanceX-linkedX-linked
Gene locationXp21 (reading frame shifted)Xp21 (reading frame maintained)
ProteinDystrophinDystrophin
Onset2- 6 years4-12 years (severe EMD)Late teenage to adulthood (mild EMD)
Severity and courseRelentlessly progressiveReduced motor function by 2-3 yearsSteady decline in strengthLife span 16 years
WeaknessProximal > distalSymmetricLegs and armsProximal > distalSymmetricLegs and arms
CardiacDilated cardiomyopathy first to second decadeOnset of signs second decadeCardiomyopathy may occur before weakness, Third to fourth decade frequent
RespiratoryProfoundly reduced vital capacity in second decadeVentilatory dependency in second decadeRespiratory involvement in subset of patientsVentilator dependency in severe patients
Muscle sizeCalf hypertrophyCalf hypertrophy
MusculoskeletalContractures: ankles, hips, and kneesScoliosis: onset after loss of ambulationContractures: ankles and others in adulthood
CNSReduced cognitive ability or reduced verbal abilitySome patients have reduced cognitive ability
Muscle pathologyEndomysial fibrosis and fatty infiltrationVariable fiber size and myopathic groupingFiber degeneration/regenerationDystrophin:absentSarcoglycans: secondary reductionVariable fiber sizeEndomysial connective tissue and fatty infiltrationFiber degenerationFiber regenerationDystrophin: reduced (usually 10-60% of normal)
Blood chemistry and hematologyCK: very high (10,000-50,000)High AST and ALT (normal GGT)High aldolaseCK: 5,000-20,000Lower levels with increasing age
