A 4-Year-Old Boy with Progressive Weakness, Difficulty Walking and Running, and Increased Falls

Duchene muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin gene. Patients with DMD present around 2–5 years of age with motor delays and non-motor delays in 1/3 of the patients. The most common motor delays are gait difficulties, toe walking, recurrent falls, inability to keep up with peers and proximal weakness. The non-motor complaints vary from autistic spectrum disorders to academic or behavioral difficulties. Physical examination reveals proximal muscle weakness, initially worse in the legs, pseudohypertrophy of the calves, lumbar lordosis, waddling gait, shortening of the Achilles tendon, hypotonia, hyporeflexia or areflexia and Gower’s sign. Laboratory investigations show elevated creatine kinase that is 10–20 times the upper limit of normal. Aldolase and other muscle enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) are also elevated. The majority of the mutations of the dystrophin gene are deletions of one or more exons, in approximately 60–65% of patients. Partial gene duplications, single nucleotide or splice variants are responsible for the other 35–40% of patients. Muscle biopsy with dystrophin protein analysis is useful to confirm the clinical diagnosis in rare “mutation-negative” cases. In those cases, a muscle biopsy reveals total absence of the dystrophin protein. Management involves steroids and multi-disciplinary care with neurology, cardiology, pulmonology and rehabilitation. New therapies that are being developed currently include gene transfer (micro-dystrophin), exon skipping, trans-splicing, genome editing, stop codon read-through and cell therapy.