A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood.

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Neurology. 2011 Feb 1;76(5):461-6.

A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood.

Yiu EM, Geevasinga N, Nicholson GA, Fagan ER, MM, Ouvrier RA.

Children's Neuroscience Centre, Royal Children's Hospital, Flemington Road,

Parkville, VIC, Australia

Abstract

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.