Overview Snapshot A 2-year-old boy presents with fatigue and difficulty with walking. The mother describes her child as “clumsy,” as he usually falls while walking. The mother also reports difficultly with climbing the stairs, which is new. The mother recalls that a relative died in his teens and also experienced muscle weakness when he was very young. On physical exam, there is weakness in the proximal muscles of the lower extremity, bilateral enlargement of the calves, and a positive Gower sign. (Duchenne muscular dystrophy) Introduction Clinical definition inherited disorder of skeletal muscle leading to progressive muscle weakness Epidemiology incidence Duchenne muscular dystrophy most common early onset form Becker muscular dystrophy a relatively common form that typically presents later in life demographics male children recall that males have only one X-chromosome Etiology X-linked recessive mutation in the dystrophin gene Duchenne muscular dystrophy frameshift or deletion of the dystrophin gene results in complete loss of dystrophin Becker muscular dystrophy non-frameshift results in partial function of dystrophin in other words, the reading frame is not disrupted Pathogenesis normal biology dystrophin is one of the largest human genes and appears to be involved in preventing muscle fiber degeneration by providing mechanical stability between the myofiber and its cell membrane connecting actin to α- and β-dystroglycan transmembrane proteins cell signaling dystrophin is expressed in cardiac, skeletal, and neural tissue pathology absent or decreased function of dystrophin leads to cycles of muscle fiber degeneration and regeneration this subsequently leads to fatty replacement and a distorted fascicular architecture Prognosis Duchenne muscular dystrophy mean age of death is 25 to 30 years of age secondary to heart failure respiratory failure Becker muscular dystrophy less severe than Duchenne muscular dystrophy Presentation Symptoms progressive muscle weakness most severe in the proximal muscles and lower extremity waddling gait Physical exam Gower sign a patient using their upper extremity to stand signifies weakness of the proximal lower extremity muscles calf pseudohypertrophy lumbar lordosis hypo- or areflexia Studies Creatine kinase elevated Muscle biopsy degeneration and regeneration muscle replacement by fat and connective tissue Genetic analysis gold standard Immunostaining absent dystrophin Differential Limb-girdle muscular dystrophy Spinal muscular atrophy Becker muscular dystrophy Treatment Approach to management treatment for both Duchenne and Becker muscular dystrophy is multidisciplinary to manage symptoms and complications e.g., physical therapy to maintain ambulation and prevent contractures Medical glucocorticosteroids indication mainstay of treatment for patients with Duchenne muscular dystrophy drugs prednisone deflazacort adverse effects weight gain hirsutism cushingoid appearance Complications Muscular wheel chair bound Cardiac dilated cardiomyopathy arrhythmia Orthopedic fractures secondary to falling