Clinical and electrophysiological phenotype of a homozygously duplicated Charcot-Marie-Tooth (type 1A) disease

Type 1A of Charcot-Marie-Tooth disease (CMT1A) is associated with a microduplication of chromosome 17 (region 17p11.2) which contains PMP22, an important gene for peripheral nerve myelination. Patients carrying two duplications are expected to have a more severe phenotype, close to the Dejerine-Sottas syndrome. In this article, we report a family of 5 CMT1A patients in whom the unrelated father and mother carry a 17p11.2 duplication. The 2 daughters carry only one duplication (one given by the father, the other given by the mother), but the son carries two 17p11.2 duplications. Interestingly, the clinical phenotype of the son is more severe (scoliosis) compared to those of his sisters, but his motor nerve conduction velocities are in the range of a heterozygote CMT1A patient. The mechanisms leading to a more severe phenotype for CMT1A are discussed and may not be strictly related to lower nerve conduction velocities.