Atypical phenotype of Charcot-Marie-Tooth disease type 1A

Two sisters with a Charcot–Marie–Tooth disease type 1A (CMT1A) duplication, who had an unusual CMT1A clinical phenotype, are described. The 63‐year‐old proband presented with dysesthesia on the inner side of the right leg. Neurological examination revealed a localized sensory disturbance in the lower extremities and mild weakness in the feet and left hand. Her 61‐year‐old sister had experienced several episodes of acute paralysis, and neurological examination showed moderate, sensory‐dominant polyneuropathy. A reduction of myelinated fibers with many onion‐bulb formations were observed in the sural nerve of the proband, and electrophysiological studies showed reduced motor nerve conduction velocities in both sisters. To diagnose CMT1A, we developed a CMT1A duplication test based on detection of CMT1A‐specific junction fragments using the long polymerase chain reaction (PCR) method. A 3.3‐kb CMT1A‐specific junction fragment was detected in both patients, and their neuropathy may therefore have been associated with CMT1A duplication. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1593–1596, 1999