Autosomal dominant Charcot-Marie-Tooth disease type 2C

Autosomal dominant Charcot-Marie-Tooth disease type 2C (CMT2C), also known as hereditary motor and sensory neuropathy type 2C (HMSN2C) or CMT2C with vocal cord and diaphragm involvement, is a rare inherited peripheral neuropathy caused by mutations in the TRPV4 gene on chromosome 12q24.11. It is classified as an axonal form of CMT disease, meaning it primarily affects the nerve fibers (axons) rather than the myelin sheath that surrounds them. CMT2C is distinguished from other forms of CMT2 by its prominent involvement of the vocal cords and diaphragm in addition to the typical features of peripheral neuropathy. Affected individuals commonly experience vocal cord paresis or paralysis, which can lead to hoarseness or a weak, breathy voice. Diaphragm weakness may cause breathing difficulties, particularly during sleep or exertion, and in severe cases may require ventilatory support. Other key features include progressive distal muscle weakness and atrophy predominantly affecting the lower limbs, reduced or absent deep tendon reflexes, and sensory loss in the hands and feet. Some patients may also develop hearing loss and skeletal abnormalities such as scoliosis. The age of onset is variable but symptoms often begin in childhood or early adulthood, and the severity can vary considerably even within the same family. There is currently no cure for CMT2C. Treatment is supportive and multidisciplinary, focusing on managing symptoms and maintaining function. This may include physical and occupational therapy to preserve muscle strength and mobility, orthotic devices such as ankle-foot orthoses, speech therapy for vocal cord involvement, and respiratory monitoring and support when diaphragm weakness is present. Surgical interventions such as vocal cord medialization may be considered for significant vocal cord paralysis. Genetic counseling is recommended for affected individuals and their families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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