Autosomal recessive intermediate Charcot-Marie-Tooth disease

Autosomal recessive intermediate Charcot-Marie-Tooth disease (AR-ICMT) is a group of rare inherited peripheral neuropathies that share features of both demyelinating (CMT type 1) and axonal (CMT type 2) forms of Charcot-Marie-Tooth disease. The term 'intermediate' refers to nerve conduction velocities (NCVs) that fall between the typical ranges for demyelinating and axonal CMT, generally between 25 and 45 m/s in the median motor nerve. This condition primarily affects the peripheral nervous system, leading to progressive weakness and atrophy of the distal muscles of the limbs, particularly the feet and hands, along with sensory impairment. Several genetic subtypes have been identified within this group, including CMTRIA (caused by mutations in the GDAP1 gene), CMTRIB (KARS1 gene), CMTRIC (PLEKHG5 gene), and CMTRID (COX6A1 gene), among others. Clinical features typically include progressive distal muscle weakness and wasting, foot deformities such as pes cavus (high-arched feet) and hammer toes, difficulty walking, reduced or absent deep tendon reflexes, and variable sensory loss affecting vibration and pain perception. Some subtypes may also present with additional features such as hearing loss, vocal cord paresis, or diaphragmatic weakness depending on the specific genetic cause. Onset is generally in childhood or adolescence, though this can vary by subtype. Disease severity ranges from mild to severe, with some patients requiring mobility aids. There is currently no cure for AR-ICMT. Treatment is supportive and symptomatic, including physical therapy and occupational therapy to maintain muscle strength and function, orthotic devices (such as ankle-foot orthoses) to improve gait, and surgical intervention for severe skeletal deformities when necessary. Pain management and regular monitoring by a multidisciplinary team including neurologists, physiatrists, and orthopedic specialists are recommended.

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