Autosomal dominant Charcot-Marie-Tooth disease type 2N

Autosomal dominant Charcot-Marie-Tooth disease type 2N (CMT2N) is a rare inherited peripheral neuropathy caused by mutations in the AARS1 gene (alanyl-tRNA synthetase 1), located on chromosome 16q22. CMT2N belongs to the axonal form of Charcot-Marie-Tooth disease (CMT type 2), meaning it primarily affects the axons of peripheral nerves rather than the myelin sheath. The peripheral nervous system is the main body system affected, leading to progressive degeneration of motor and sensory nerves, particularly in the distal extremities. Key clinical features include progressive distal muscle weakness and atrophy, predominantly affecting the lower limbs initially, with later involvement of the hands and forearms. Patients typically experience difficulty walking, foot deformities such as pes cavus (high-arched feet) and hammer toes, and reduced or absent deep tendon reflexes. Sensory symptoms including decreased sensation to touch, pain, and vibration in the feet and hands may also occur. Nerve conduction studies generally show normal or near-normal conduction velocities with reduced amplitudes, consistent with an axonal neuropathy. There is currently no cure or disease-modifying therapy for CMT2N. Management is supportive and symptomatic, including physical therapy to maintain muscle strength and flexibility, occupational therapy, orthotic devices (such as ankle-foot orthoses) to improve gait stability, and pain management when needed. Surgical intervention may be considered for severe foot deformities. Regular monitoring by a neurologist and a multidisciplinary rehabilitation team is recommended to optimize quality of life and functional independence.

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