Charcot-Marie-Tooth disease type 4H

Charcot-Marie-Tooth disease type 4H (CMT4H), also known as hereditary motor and sensory neuropathy Russe type (HMSNR), is a rare autosomal recessive demyelinating peripheral neuropathy. It was originally described in the Romani (Gypsy) population of Russe, Bulgaria, and is predominantly found in Romani communities across Europe. CMT4H is caused by mutations in the FGD4 gene (also known as FRABIN), which encodes a guanine nucleotide exchange factor involved in actin cytoskeleton regulation and myelination of peripheral nerves. The disease primarily affects the peripheral nervous system, leading to progressive weakness and wasting of the distal muscles of the limbs, particularly the feet and hands. Onset typically occurs in childhood, usually between the ages of 8 and 16 years. Key clinical features include progressive difficulty walking, foot deformities (such as pes cavus and hammer toes), distal muscle atrophy and weakness in the lower and upper extremities, reduced or absent deep tendon reflexes, and sensory loss. Nerve conduction velocities are markedly reduced, consistent with a demyelinating neuropathy. The disease progresses slowly, and many patients eventually require mobility aids. There is currently no cure or disease-modifying treatment for CMT4H. Management is supportive and symptomatic, including physical therapy and rehabilitation to maintain muscle strength and flexibility, orthopedic devices such as ankle-foot orthoses to assist with walking, and surgical interventions for severe foot deformities when necessary. Occupational therapy may help patients maintain hand function. Regular monitoring by a multidisciplinary team including neurologists, orthopedic specialists, and rehabilitation professionals is recommended to optimize quality of life.

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