Objective: X-linked Charcot-Marie-Tooth disease (CMTX) is infrequently diagnosed in childhood, and its clinical and neurophysiologic features are not well-described. We reviewed clinical, neurophysiologic, and pathologic findings in 17 children with CMTX.
Methods: This was a retrospective review of children with CMTX from 2 tertiary pediatric hospitals. The diagnosis of CMTX was based on an identifiable connexin 32 mutation (CMTX1) or a consistent pedigree and neurophysiologic features in children without a connexin 32 mutation (CMTX-other).
Results: Six boys and 2 girls from 8 kindreds had CMTX1, and 8 boys and 1 girl from 5 kindreds had other forms of CMTX (CMTX-other). Fifteen children, including males and carrier females, were symptomatic from infancy or early childhood (younger than 5 years). In addition to the typical Charcot-Marie-Tooth disease clinical phenotype, some patients had delayed motor development, sensorineural hearing loss, tremor, pathologic fractures, or transient CNS disturbances. Eleven children underwent nerve conduction studies. Median nerve motor nerve conduction velocities were in the intermediate to normal range (30-54 m/s) in all children older than 2 years. Axon loss, reflected by low-amplitude compound muscle action potentials, was present in all patients. A pattern of X-linked dominant inheritance, with carrier females showing an abnormal neurologic or neurophysiologic examination, correlated with the presence of a connexin 32 mutation in all but 2 pedigrees.
Conclusions: The clinical phenotype of CMTX is broader than previously reported. Onset in males and carrier females is most often in early childhood. Families with an X-linked dominant inheritance pattern are likely to have CMTX1.