The clinical signs and genetic analysis of early-onset Charcot-Marie-Tooth disease (CMT) in a 2-year-old boy and members of his family are reported from the Academic Medical Center, Amsterdam, and Sophia Children’s Hospital, Rotterdam, the Netherlands. The proband was seen at 2.5 years of age because of toe walking and severe pes equinovarus for which he had surgery at 2 years. He had bilateral foot drop, atrophy of lower legs, genu recurvatum, and absent deep tendon reflexes. The diagnosis of CMT was also suspected in both parents because of corrected pes cavus and Achilles tenotomies in their teens. Vibration sense was diminished in the toes, motor and sensory NCVs were decreased, and deep tendon reflexes wee absent. The mother’s father and a paternal aunt had CMT, and the father’s father, his brother, and sister had bilateral pes cavus. On genetic analysis, the boy was heterozygous for both peripheral myelin protein 22 (PMP22) duplication and a mutation in LITAF gene, while each parent had only one mutated CMT gene. [1]

COMMENT. A compound phenotype in a severe case of CMT1 is identified by molecular genetic analysis. This more severe phenotype resulted from the co-occurrence of both PMP22 duplication and a LITAF mutation. Modifier genes can alter the severity of CMT caused by PMP22 duplication. In addition to PMP22 and LITAF, 4 other genes (MPZ, GJB1, EGR2, and NEFL) have been identified for autosomal dominant demyelinating neuropathies (Young, Suter, 2003; cited by authors).