Autosomal dominant Charcot-Marie-Tooth disease type 2L

Autosomal dominant Charcot-Marie-Tooth disease type 2L (CMT2L) is a rare inherited peripheral neuropathy caused by mutations in the HSPB8 gene (also known as HSP22), which encodes a small heat shock protein involved in protein quality control and autophagy. CMT2L is also referred to as hereditary motor and sensory neuropathy type 2L. It belongs to the axonal form of Charcot-Marie-Tooth disease (CMT2), meaning the primary pathology affects the nerve axons rather than the myelin sheath, and nerve conduction velocities are typically normal or near-normal while amplitudes are reduced. The disease primarily affects the peripheral nervous system, leading to progressive distal muscle weakness and atrophy, predominantly in the lower limbs. Patients typically develop difficulty walking, foot deformities such as pes cavus (high-arched feet) and hammer toes, and sensory loss in a stocking-glove distribution. Onset is variable but often occurs in adulthood, though earlier presentations have been reported. Upper limb involvement may develop as the disease progresses. Some patients with HSPB8 mutations may present with a predominantly motor phenotype overlapping with distal hereditary motor neuropathy type II (dHMN-II/HMN2A). There is currently no cure or disease-modifying treatment for CMT2L. Management is supportive and multidisciplinary, including physical therapy to maintain muscle strength and flexibility, occupational therapy, orthotic devices such as ankle-foot orthoses to improve gait, and orthopedic surgery when needed for foot deformities. Pain management may be necessary for neuropathic symptoms. Regular monitoring by a neurologist is recommended to track disease progression.

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