A 3-year-old boy is brought to the office by his parents. They say that the child cannot keep up with his cousin, who is the same age. The boy climbs up from a squat by using his hands to push off the ground and his lower extremities. His calves appear enlarged on physical examination. This patient's condition is most likely associated with which of the following?

Question

A 3-year-old boy is brought to the office by his parents.  They say that the child cannot keep up with his cousin, who is the same age.  The boy climbs up from a squat by using his hands to push off the ground and his lower extremities.  His calves appear enlarged on physical examination.  This patient's condition is most likely associated with which of the following?

Quizplus · Accepted Answer

11ec160b_3a56_2c37_9249_fbb78ac89c3b_MD0001_00 Muscular dystrophy is a term that applies to the various diseases that manifest with progressive muscular weakness. Deletions of the dystrophin gene that encodes the dystrophin protein on X chromosome p21 are the most common mutation in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Deletions that are not a multiple of 3 change the reading frame, causing a frameshift mutation, which results in a nonfunctional protein and severe clinical manifestations (DMD). In contrast, deletions that are a multiple of 3 base pairs preserve the reading frame, resulting in a truncated but functional protein and a milder clinical phenotype (BMD). Dystrophin is a structural component of skeletal muscle fibers that provides mechanical stability to the sarcolemma. It links a component of the cytoskeleton (actin) to transmembrane proteins (α- and β-dystrophiglycans) that are connected to the extracellular matrix. Loss of dystrophin results in cellular injury (myonecrosis). On light microscopy, there is segmental degeneration and regeneration of the myofibers with marked variation in size (both atrophic and hypertrophic fibers). Over time, the muscle tissue undergoes progressive fatty replacement. On clinical examination, the presence of Gowers sign and calf enlargement in a boy age 2-5 is classic for DMD. Calf hypertrophy allows affected children to overcome proximal muscle weakness, but it is later replaced by fat and connective tissue (pseudohypertrophy). The Gowers sign involves the use of one's hands to rise from a squat or from a chair to compensate for proximal muscle weakness. (Choice A) Endomysial inflammatory infiltration is found on muscle biopsy in polymyositis. Dermatomyositis is associated with perifascicular inflammation. Both diseases cause proximal muscle weakness but not distal muscle hypertrophy. (Choice B) Endoneural inflammatory infiltration is characteristic of Guillain-Barré syndrome, which classically manifests as ascending flaccid paralysis and hyporeflexia. (Choice C) Examples of ion channel myopathies include hyper- and hypokalemic periodic paralysis, which present with episodic, painless muscle weakness. (Choice D) Charcot-Marie-Tooth disease is due to mutation of the genes responsible for myelin synthesis. Affected patients frequently present with distal muscle weakness, sensory loss, and atrophy of the calf muscles (producing the characteristic stork leg deformity). (Choice F) Mutations involving sarcomere proteins are responsible for hypertrophic cardiomyopathy and certain forms of familial dilated cardiomyopathy. Educational objective: Duchenne muscular dystrophy is an X-linked recessive myopathy that manifests with proximal muscle weakness and enlargement of the calf muscles in boys age 2-5. It most often results from frameshift deletions affecting the dystrophin gene. Dystrophin provides a stabilizing interaction between the sarcolemma and the intracellular contraction apparatus, and disruption of the protein results in membrane damage and myonecrosis. __________ References: Muscle disease. (http://www.ncbi.nlm.nih.gov/pubmed/24488829) Clinical aspects, molecular pathomechanisms and management of myotonic dystrophies. (http://www.ncbi.nlm.nih.gov/pubmed/24803843) Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. (http://www.ncbi.nlm.nih.gov/pubmed/16770791)

A 3-Year-Old Boy Is Brought to the Office by His