A 15-year-old boy is evaluated for progressive lower extremity weakness. The patient has had difficulty running and keeping up with peers for the past several years and has sprained his ankles on multiple occasions. His father also experienced similar symptoms beginning at the same age and became wheelchair bound. Physical examination shows weakness and atrophy of the distal lower extremity muscles. There is bilateral pes cavus deformity. Ankle reflexes are absent, and sensation to vibration is also absent in the feet. Abnormal function of which of the following is the most likely cause of this patient's condition?

Question

A 15-year-old boy is evaluated for progressive lower extremity weakness.  The patient has had difficulty running and keeping up with peers for the past several years and has sprained his ankles on multiple occasions.  His father also experienced similar symptoms beginning at the same age and became wheelchair bound.  Physical examination shows weakness and atrophy of the distal lower extremity muscles.  There is bilateral pes cavus deformity.  Ankle reflexes are absent, and sensation to vibration is also absent in the feet.  Abnormal function of which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

11ec160b_39b4_bcdd_9249_a119d7b935fd_MD0001_00 This adolescent with lower extremity weakness, muscle atrophy, and peripheral neuropathy (ie, decreased vibratory sense, absent ankle reflex) likely has Charcot-Marie-Tooth disease (CMT). CMT is a group of hereditary peripheral neuropathies characterized by mutations in genes coding for peripheral nerve axonal or myelin proteins. The most common subtype, CMT1, occurs due to an autosomal dominant mutation in the PMP22 gene. Manifestations of CMT depend on the underlying genetic abnormality; however, most cases present in adolescence or early adulthood with progressive, symmetric distal muscle atrophy and weakness. Initial manifestations often include frequent ankle sprains or difficulty with exercise. Physical examination typically demonstrates muscle wasting most prominent in the distal lower extremities, with sensory loss, areflexia, pes cavus (ie, high arches), and hammer toes. Upper extremity involvement (ie, intrinsic musculature of the hands) typically occurs later in the disease course. (Choice A) Duchenne and Becker muscular dystrophy are X-linked inherited disorders caused by abnormalities in muscle dystrophin. Patients also develop distal limb weakness but present with a waddling gait and pseudohypertrophy (rather than atrophy) of the calf muscles. (Choice C) Malignant hyperthermia occurs in patients with abnormal ryanodine receptors, which allow excessive calcium accumulation within the skeletal muscle when exposed to volatile anesthetics (eg, halothane, isoflurane). This results in sustained muscle contraction, leading to muscle rigidity, hyperthermia, hypercarbia, and rhabdomyolysis. (Choice D) Botulinum toxin cleaves SNARE proteins within neurons, preventing the synaptic vesicle from fusing to the cell membrane and releasing neurotransmitters. Botulism typically causes acute-onset cranial neuropathies (eg, dysarthria, ptosis) and descending muscle weakness after toxin ingestion (eg, eating contaminated home-canned food) or spore exposure (eg, giving honey to an infant). Muscle wasting is unexpected. (Choice E) Hyperphosphorylated tau protein is seen in multiple neurodegenerative diseases (eg, Alzheimer dementia, frontotemporal dementia). These typically occur in elderly patients and present with progressive impairments in cognitive function, not muscle atrophy. Educational objective: Charcot-Marie-Tooth is a group of hereditary peripheral neuropathies characterized by mutations in genes coding for peripheral nerve axonal or myelin proteins. Manifestations typically include progressive, symmetric distal muscle atrophy and weakness most prominent in the feet and calf musculature, with sensory loss, areflexia, pes cavus (ie, high arches), and hammer toes.

A 15-Year-Old Boy Is Evaluated for Progressive Lower Extremity Weakness