Autosomal dominant Charcot-Marie-Tooth disease type 2M

Autosomal dominant Charcot-Marie-Tooth disease type 2M (CMT2M) is a rare inherited peripheral neuropathy caused by mutations in the DNM2 gene, which encodes dynamin 2, a protein involved in membrane trafficking and endocytosis. CMT2M belongs to the broader group of Charcot-Marie-Tooth type 2 diseases, which are characterized by axonal degeneration of peripheral nerves rather than demyelination. The condition primarily affects the peripheral nervous system, leading to progressive distal muscle weakness and atrophy, predominantly in the lower limbs, along with sensory impairment. Patients may also develop foot deformities such as pes cavus (high-arched feet) and hammer toes. The age of onset in CMT2M is variable but often occurs in childhood or adolescence, though later onset has been reported. Key clinical features include progressive difficulty with walking, distal limb weakness (particularly in the legs), reduced or absent deep tendon reflexes, and mild to moderate sensory loss affecting vibration and proprioception. Some patients may experience upper limb involvement as the disease progresses. Nerve conduction studies typically show reduced compound muscle action potential amplitudes with relatively preserved nerve conduction velocities, consistent with an axonal neuropathy. There is currently no cure or disease-modifying treatment for CMT2M. Management is supportive and symptomatic, including physical therapy to maintain muscle strength and flexibility, occupational therapy, orthotic devices such as ankle-foot orthoses to assist with gait, and surgical intervention for significant skeletal deformities when necessary. Pain management may also be required. Regular follow-up with a multidisciplinary team including neurologists, rehabilitation specialists, and orthopedic surgeons is recommended to optimize quality of life and functional independence.

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