CMT1A ASSOCIATED WITH 17p11.2 DUPLICATION AND ASYMMETRICAL LEG MUSCLE HYPERTROPHY

Charcot‐Marie‐Tooth disease (CMT) is the most common inherited disorder of the peripheral nervous system. It is characterized by distal muscle weakness and atrophy, first involving legs and particularly the peroneal muscles with the typical leg as “inverted champagne bottle”. The CMT1A is an autosomal dominant demyelinating sensorimotor neuropathy most often associated with a duplication of chromosome 17p11.2, a region that contains the gene for the peripheral protein 22 (PMP22). We describe two families with CMT1A, in which three of six members did not show the typical feature of leg atrophy. In fact, a patient belonging to the first family showed a bilateral symmetric hypertrophy of the calf. In the second family, a patient had an asymmetric bilateral calf hypertrophy, and his son showed a similar condition but the asymmetric hypertrophy involved the whole left limb. The other cardinal features in our family were distal weakness of lower limbs (5 of 6), pes cavus (3 of 6), and reduced or absent tendon reflexes (6 of 6). Motor and sensory conduction velocities showed, in all nerves explored, values at or below 38 m/sec. The computed tomography of lower limbs showed that leg enlargement was due to true muscle hypertrophy without concomitant increase of adipose or connective tissue. The pathophysiological mechanisms responsible for muscle enlargement are yet unclear. It is possible that one or more genetic factors, still unknown, may be linked genetically to the neuropathy in such pedigrees in which most or all affected members carry the trait.