Autosomal dominant Charcot-Marie-Tooth disease type 2D

Autosomal dominant Charcot-Marie-Tooth disease type 2D (CMT2D), also known as hereditary motor and sensory neuropathy type 2D or distal hereditary motor neuropathy type V (dHMN-V), is a rare inherited peripheral neuropathy caused by mutations in the GARS1 gene (glycyl-tRNA synthetase 1) on chromosome 7p14.3. CMT2D belongs to the axonal form of Charcot-Marie-Tooth disease, meaning it primarily affects the nerve fibers (axons) themselves rather than the myelin sheath that surrounds them. The disease predominantly affects the peripheral nervous system, particularly the motor and sensory nerves supplying the hands and feet. CMT2D is characterized by a distinctive pattern of weakness and wasting that preferentially affects the upper limbs, particularly the small muscles of the hands, which is relatively unusual among CMT subtypes. Patients typically present with difficulty performing fine motor tasks such as buttoning clothes, writing, or gripping objects. Lower limb involvement, including foot drop and distal leg weakness, may also occur but is often less prominent. Sensory loss, when present, tends to be mild and affects vibration and pain perception in the distal extremities. Nerve conduction studies typically show normal or near-normal conduction velocities with reduced amplitudes, consistent with an axonal neuropathy. Onset is usually in the teenage years or early adulthood, though it can vary from childhood to later in life. There is currently no cure or disease-modifying treatment for CMT2D. Management is supportive and symptomatic, including physical and occupational therapy to maintain strength and function, orthotic devices such as hand splints or ankle-foot orthoses, and pain management when needed. Surgical intervention may occasionally be considered for skeletal deformities. Genetic counseling is recommended for affected individuals and their families given the autosomal dominant inheritance pattern, meaning each child of an affected parent has a 50% chance of inheriting the condition.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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