CMT X Spectrum in Childhood

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CMT X Spectrum in Childhood

ANN Poster Session Seattle Thursday, April 30, 2009 7:00 AM

[P07.174] The Clinical Spectrum of X-Linked Charcot-Marie-Tooth Disease in

Childhood

Eppie M. Yiu, Parkville, , Australia, Nimeshan Geevasingha, Westmead,

NSW, Australia, Garth Nicholson, Sydney, New South Wales, Australia,

Fagan, A. Ouvrier, Westmead, NSW, Australia, M. , Parkville,

, Australia

OBJECTIVE: We reviewed clinical and neurophysiologic findings in a cohort of

pediatric patients with X-linked Charcot-Marie-Tooth disease (CMTX).

BACKGROUND: CMTX, the second most common form of CMT is most commonly caused by

mutations in GJB1 (designated CMTX1). CMTX is rarely recognised in childhood,

and the clinical features in this age group are not well described.

DESIGN/METHODS: Retrospective review of patients with CMTX from the Children's

Hospital at Westmead Sydney, and The Royal Children's Hospital Melbourne. The

diagnosis of CMTX was based on an identifiable GJB1 mutation (CMTX1), or a

consistent pedigree and neurophysiologic features in children without a GJB1

mutation (non-CMTX1).

RESULTS: Eighteen children (15 boys and three girls) were identified from 12

families. Five boys and two girls had CMTX1, and ten boys and one girl

non-CMTX1. Age of onset was one month to 13 years, with 16 children having onset

in early childhood (less than 5 years). Clinical features included pes cavus,

gait abnormalities, length dependent wasting and weakness, and distal areflexia.

Less common features included sensorineural hearing loss, hand tremor,

pathologic fractures and transient central nervous system disturbances. Fourteen

children underwent nerve conduction studies. Median nerve motor nerve conduction

velocities were in the intermediate to normal range (30 54 m/sec) in all

children aged over 2 years. Axon loss, reflected by low amplitude compound

muscle axon potentials was present in all patients. Temporal dispersion was seen

in two patients. The presence of X-linked dominant inheritance, with carrier

females showing an abnormal neurologic and/or neurophysiologic examination

correlated with the presence of a GJB1 mutation in all but two pedigrees.

CONCLUSIONS/RELEVANCE: 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.