CMT2B

Charcot–Marie–Tooth disease type 2B (CMT2B) is a hereditary sensorimotor neuropathy classified as an axonal form of Charcot–Marie–Tooth disease. It is caused by heterozygous mutations in the RAB7A gene, which encodes Rab7A, a small GTPase involved in late endosome–lysosome trafficking and intracellular transport. The condition follows autosomal dominant inheritance, with most cases arising de novo or transmitted from an affected parent.

Clinically, CMT2B presents with distal weakness and atrophy, particularly in the feet and hands, with sensory impairment in the same regions. Foot deformities such as pes cavus are common, and reflexes are often reduced or absent. A characteristic feature is recurrent ulcers of distal digits (fingers or toes) due to impaired sensation and repetitive trauma. Onset typically occurs in adolescence or early adulthood, and progression is variable.

Diagnosis combines clinical evaluation, neurologic examination, and nerve conduction studies that show an axonal pattern (reduced compound muscle action potential amplitudes with relatively preserved conduction velocities). Genetic testing confirms a pathogenic RAB7A variant. Differential diagnosis includes other CMT subtypes and distal hereditary motor or sensory neuropathies.

There is no cure for CMT2B. Management is supportive and multidisciplinary, focusing on physical and occupational therapy, orthotic devices for foot stabilization, orthopedic interventions for deformities when needed, pain management, skin and ulcer care, and regular monitoring. Genetic counseling is advised due to the autosomal dominant inheritance and variable expressivity. Prognosis varies, with many individuals experiencing slow progression or stabilization of symptoms over time.