(D) (Becker's muscular dystrophy) (3492-95 H 18th)* Becker muscular dystrophy differ from Duchene muscular dystrophy by its (595- Ghai 8th)* Later age of onset (usually >6 years of age)* Later age of wheelchair confinement (>15 years)* More incidence of myalgias* Occasional rhabdomyolysis following exercise and early cardiomyopathyPresence of muscular weakness in association with positive Gower's sign, hypertrophy of calves (pseudohypertrophy) and elevated CPK values in a young male suggests a diagnosis of Duchenne's muscular dystrophy.Essentials of Diagnosis; Duchenne Muscular Dystrophy; Current Diagnosis & Treatment Neurology * Typically affects males* Positive family History (X-linked recessive inheritance)* Onset before 5 years of age with delayed motor milestones* Proximal muscle weakness, positive Gower's sign and calf muscle pseudohypertrophy (common)* Elevated CK levels (>10 fold increase)* Severely reduced or absent dystrophin in muscle biopsy or genetic testing provides definitive diagnosisDuchenne Muscular Dystrophy (pseudohypertrophic Muscular Dystrophy; ReviewDuchenne's muscular dystrophy is the most common hereditary neuromuscular disease affecting all races and ethnic groupInheritance and pathology* Duchenne's muscular dystrophy is inherited as an x-Linked Recessive disorder9* It is caused by a multation in the gene responsible for producing dystrophin9* Dystrophin is a subsarcolemmal protein9 localized to the inner surface of the sarcolemma9 of the muscle fibre* Lack of dystrophin protein results in weakness of sarcolemma, causing membrane tears and muscle fibre necrosis, therepy resuiting in muscle weaknessPresentation & clinical Manifestations* Typically affects males & family histoy is positive (X Linked recessive inheritance)* Typically present between ages 3 and 5 (Disorder docs not present at birth9 or infancy) (Delayed motor milestones may be apparent after the first year of life)* Gower's sign is positive9* Pseudohypertrophy of calf is seen9 (muscle is replaced by fat & connective tissue)* Loss of muscle strength is progressive9* Proximal muscle and neck flexors are involved more9* Leg involvement is more severe than arm involvement* Contractures of heel cords and iliotibial band occurs (by age of 6 years)* Progressive scoliosis developsComplicationsChest deformity9 (Scoliosis)9;Impairs pulmonary function9By age of 16 and 18 years patients are predisposed to serious pulmonary fatal infectionsCardiacCardiomyopathy9 and CHF may be seenCardiac cause of death is uncommonIntelectual impairment;is common9 (IQ is one SD below the mean)Remember: Onset9Before age of 59 Confined to wheel chairInability to walkAfter age of 129 Respiratory failureIn second or third decade (after 16-18years)9 Progressive Musclear DystrophiesTypeInheritanceDefective Gene/proteinOnset AgeClinical featuresOther organ system involvedDuchenne'sXRDystrophinBefore 5 yearsProgressive weakness of girdle muscles unable to walk after age 12 progressive kyphoscoliosis Respiratory failure in 2nd or 3rd decadeCardiomyopathy Mental impairmentBecker'sXRDystrophinEarly childhood to adultProgressive weakness of girdle muscle Able to walk after age 15 Respiratory failure may develop by 4th decadeCardiomyopathyLimb-girdleAD/ARSeveralEarly childhood to early adultSlow progressive weakness of shoulder and hip girdle muscles+- CardiomyopathyEmery-DreifussXR/ADEmerin/Lamins A/C Nesprin-1, Nesprin 2, TMEM43Childhood to adultElbow contractures, umeral and peroneal weaknessCardiomyopathyCongenitalARSeveralAt birth or within first few monthsHypotonia, contractures, delayed milestones progression to respiratory failure in some; static course in othersCNS abnormalities (hypomyelination,malform ation) Eye abnormalitiesMyotonic (DMI,DM2)ADDM1; Expansion CTG repeat DM2; Expansion CCTG repeatChildhood to adult Maybe infancy if mother affected (DMI Only)Slowly progressive weakness of face, shoulder girdle, and foot dorsiflexion preferential proximal weakness in DM2Cardiac conduction defectsMental impairment cataracts frontal baldness Gonadal atrophyFacioscapulohumeralADDUX44qChildhood to adultSlowly progressive weakness fo face, shoulder girdle, and foot dorsiflexionDeafness coats (eye)diseaseOculopharyngealADExpansion, poly- A RNA binding protein5th to 6th decadeSlowly progressive weakness of extraocular, pharyngeal, and limb muscles