Summary

Charcot-Marie-Tooth disease, type 4B1 (CMT4B1) is a severe early-onset demyelinating CMT peripheral sensorimotor polyneuropathy. It was initially described in an Italian family and around 10 additional families have been described so far (including further families from Italy, and Saudi Arabia). Onset occurs during early childhood with distal and proximal muscular weakness starting in the lower extremities, sensory loss and cranial nerve involvement. Foot deformities (pes equinovarus) are frequent and diaphragmatic and facial involvement has been reported. Nerve conduction velocities are reduced and nerve biopsies reveal demyelization with characteristic myelin outfoldings in the peripheral nerve. The clinical and pathological features of CMT4B1 and CMT4B2 (see this term) are very similar. CMT4B1 is transmitted in an autosomal recessive manner and is caused by mutations in the gene encoding myotubularin-related protein 2 (MTMR2; 11q22), involved in polyphosphoinositide signaling. Patients are severely handicapped and wheelchair-bound by the third decade of life. Death in the fourth or fifth decade of life has been reported, probably due to respiratory insufficiency.

Expert reviewer(s)

• Dr Carmen ESPINÓS
• Pr Francesc PALAU