Overview Snapshot A 4-year-old boy is brought to his pediatrician by his mother for muscle weakness. She reports that he has trouble running with his friends and climbing the stairs. She also states that the patient has increased difficulty arising from a seated position on the ground and walks in a "waddling" way. On physical exam, there is significant proximal muscle weakness and pseudohypertrophy of the bilateral calves. He also has Gower sign. Laboratory testing is notable for a significantly elevated creatine kinase and aldolase. A sample is obtained for genetic analysis of the dystrophin gene. (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 25-30 years of age and death results from 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 Labs ↑ serum creatine kinase ↑ aldolase, alanine transaminase, and aspartate transaminase Genetic testing confirms the diagnosis Dystrophin analysis Duchenne muscular dystrophy complete or almost complete loss of dystrophin Becker muscular dystrophy dystrophin with abnormal molecular weight reduced quantity of dystrophin Biopsy muscle fibril degeneration, regeneration, and isolated fiber hypertrophy muscle replacement with fat and connective tissue performed if genetic testing is negative Differential Limb-girdle muscular dystrophy Spinal muscular atrophy Treatment Management approach treatment for both Duchenne and Becker muscular dystrophy is multidisciplinary to manage symptoms and complications 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