The Clinical Spectrum of X-Linked Charcot-Marie Tooth Disease in Childhood

  • Dr Eppie Yiu, Royal Children's Hospital Melbourne, Australia
  • Dr Nimeshan Geevasinga, The Children's Hospital at Westmead, Australia
  • Prof Garth Nicholson, Concorde Hospital Sydney, Australia
  • Prof Robert Ouvrier, The Children's Hospital at Westmead, Australia
  • Dr Monique Ryan, Royal Children's Hospital Melbourne, Australia

    • Objectives

    X-linked Charcot-Marie-Tooth disease (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. We reviewed clinical, neurophysiologic and pathological findings on a cohort of paediatric patients with CMTX.

    Methods

    A retrospective review of patients with CMTX treated at 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/or neurophysiological features in children without a GJB1 mutation (non-CMTX1).

    Results

    Seventeen patients (14 male and three female) were identified. Five males and two females had CMTX1, and nine males and one female non-CMTX1. Age of onset was six months to 13 years, mean 6.3 years. At least one patient was symptomatic from early infancy. Clinical features included pes cavus, gait abnormalities, length dependent wasting and weakness, and distal areflexia. Less common features included sensorineural hearing loss, tremor, pathologic fractures and transient central nervous system disturbances. Intermediate median motor nerve conduction velocities in children above age two years (male and female) were seen (ranging from 30 -54 m/sec), with lower amplitude motor responses in the lower extremities. Temporal dispersion was present in two patients.

    Conclusions

    The clinical phenotype of CMTX is broader than previously reported, with some cases presenting early in life and with symptoms being apparent in some carrier females, even in childhood.