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We report two siblings of Indian origin with no known consanguinity who presented with early onset severe Charcot-Marie-Tooth (CMT) disease. They demonstrated features of CMT type 1 and CMT type 2J. Genetic analysis confirmed heterozygosity in both siblings, carrying peripheral myelin protein 22 (PMP22) duplication and a novel variant myelin protein zero (MPZ) mutation. Each parent contributed to one of the two mutations. Pupil abnormalities were the key to the diagnosis of compound CMT disease in this kindred, and we encourage further genetic testing in atypical CMT disease cases. We also propose that MPZ mutations should be preferentially tested in the presence of pupil abnormalities.
Proband 1 (III:6)
The 33-year-old elder sister presented with muscle wasting in the hands coupled with walking difficulty. She had delayed walking aged 18 months, and was unable to take part in sports. She developed pes cavus, grip weakness and reduced sensation in all extremities in her teenage years. She had corrective surgery for scoliosis and tendon transfers of her feet. She continued to deteriorate and required the use of a mobility scooter. Neurological examination showed findings of a severe sensorimotor neuropathy, with reduced tone, severe symmetrical distal weakness in both upper and lower limbs with wasting, areflexia, reduced distal sensation in all modalities and sensory ataxia. There was tongue fasciculation and mild sensorineural hearing loss in the …