Autosomal dominant Charcot-Marie-Tooth disease type 2I

Autosomal dominant Charcot-Marie-Tooth disease type 2I (CMT2I) is a rare inherited peripheral neuropathy caused by mutations in the MPZ (myelin protein zero) gene located on chromosome 1q23.3. CMT2I belongs to the axonal subgroup of Charcot-Marie-Tooth disease (CMT type 2), meaning it primarily affects the peripheral nerve axons rather than the myelin sheath, although MPZ is a myelin-related gene. This condition is also sometimes referred to as CMT2I or late-onset CMT2 due to MPZ mutations, and it is allelic with CMT1B (a demyelinating form) and Dejerine-Sottas disease caused by the same gene. CMT2I primarily affects the peripheral nervous system, leading to progressive distal muscle weakness and atrophy, particularly in the lower legs and feet, as well as 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 is common, and some patients may develop hearing loss or pupillary abnormalities. The age of onset in CMT2I is generally later than in many other CMT subtypes, often presenting in adulthood, though variability exists even within families. Nerve conduction studies typically show reduced amplitudes with relatively preserved or mildly reduced conduction velocities, consistent with an axonal neuropathy pattern. There is currently no cure or disease-modifying treatment for CMT2I. 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 multidisciplinary team including neurologists, physiatrists, and orthopedic specialists is recommended to optimize quality of life and functional independence.

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