This 2009 Lancet Neurology review covers the diagnosis, natural history, and management of Charcot-Marie-Tooth disease, the most common inherited neuromuscular disorder. It addresses nerve-conduction-velocity-based classification of CMT subtypes, characterizes the clinical course across genotypes, and reviews rehabilitation and surgical options for skeletal deformities. No proven disease-modifying drug therapy existed at the time of publication.
The classic CMT presentation — pes cavus, steppage gait, distal muscle wasting, absent deep-tendon reflexes, positive family history. Should prompt nerve-conduction studies before genetic testing.
A median or ulnar motor nerve-conduction velocity below 38 m/s confirms demyelinating CMT1; above 38 m/s points to axonal CMT2. When velocity falls in the 25-45 m/s intermediate range, think CMTX1 first, particularly in men without male-to-male transmission. This single distinction determines which genes you test and in what order.
For the orthopedic surgeon, two principles stand out: scoliosis affects up to 1 in 4 CMT patients and requires active surveillance, and triple arthrodesis for fixed cavovarus carries a documented long-term risk of adjacent joint arthritis that belongs in every consent discussion.
Because no drug currently modifies disease progression, counsel patients that mild-to-moderate exercise is beneficial, high-resistance training should be avoided, and neurotoxic chemotherapy agents (vinca alkaloids, cisplatin, taxols) can precipitate acute neuropathy resembling Guillain-Barré syndrome. Flag these to oncology whenever a CMT patient faces cancer treatment.
This 2009 Lancet Neurology review covers the diagnosis, natural history, and management of Charcot-Marie-Tooth disease, the most common inherited neuromuscular disorder. It addresses nerve-conduction-velocity-based classification of CMT subtypes, characterizes the clinical course across genotypes, and reviews rehabilitation and surgical options for skeletal deformities. No proven disease-modifying drug therapy existed at the time of publication.
The classic CMT presentation — pes cavus, steppage gait, distal muscle wasting, absent deep-tendon reflexes, positive family history. Should prompt nerve-conduction studies before genetic testing.
A median or ulnar motor nerve-conduction velocity below 38 m/s confirms demyelinating CMT1; above 38 m/s points to axonal CMT2. When velocity falls in the 25-45 m/s intermediate range, think CMTX1 first, particularly in men without male-to-male transmission. This single distinction determines which genes you test and in what order.
For the orthopedic surgeon, two principles stand out: scoliosis affects up to 1 in 4 CMT patients and requires active surveillance, and triple arthrodesis for fixed cavovarus carries a documented long-term risk of adjacent joint arthritis that belongs in every consent discussion.
Because no drug currently modifies disease progression, counsel patients that mild-to-moderate exercise is beneficial, high-resistance training should be avoided, and neurotoxic chemotherapy agents (vinca alkaloids, cisplatin, taxols) can precipitate acute neuropathy resembling Guillain-Barré syndrome. Flag these to oncology whenever a CMT patient faces cancer treatment.