Autosomal dominant Charcot-Marie-Tooth disease type 2A1

Autosomal dominant Charcot-Marie-Tooth disease type 2A1 (CMT2A1) is a rare inherited peripheral neuropathy caused by mutations in the KIF1B gene on chromosome 1p36. It belongs to the broader group of Charcot-Marie-Tooth type 2 diseases, which are characterized by axonal degeneration of peripheral nerves rather than demyelination. CMT2A1 primarily affects the peripheral nervous system, leading to progressive weakness and atrophy of the distal muscles, particularly in the lower legs and feet, and later in the hands. 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 loss in the extremities, particularly affecting vibration and position sense, is also common. The disease usually presents in childhood or adolescence, though the age of onset and severity can vary even within the same family. Nerve conduction studies typically show normal or near-normal conduction velocities (above 38 m/s), which distinguishes CMT type 2 from the demyelinating CMT type 1 forms. CMT2A1 is very rare, with only a limited number of families reported with confirmed KIF1B mutations; the majority of axonal CMT2A cases are instead caused by MFN2 mutations (classified as CMT2A2). There is currently no cure or disease-modifying treatment for CMT2A1. Management is supportive and includes physical therapy, occupational therapy, orthotic devices to improve mobility, and surgical intervention for severe foot deformities when necessary. Pain management and regular monitoring by a multidisciplinary team including neurologists and rehabilitation specialists are recommended.

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