X-LINKED CHARCOT-MARIE-TOOTH DISEASE IN CHILDHOOD

Objectives: Charcot-Marie-Tooth disease is the second most common form of inherited neuropathy but is rarely recognised in childhood. We reviewed clinical, neurophysiologic and nerve pathology findings in a cohort of paediatric patients with CMTX.

Methods: Ten patients were identified. The diagnosis of X-linked CMT was based on genetic analysis (identifiable connexin 32 mutation, CMTX1) or on consistent pedigree with negative genetic testing (connexin 32 mutation negative, CMTX2/CMTX3).

Results: Age of the patients at presentation ranged from 5–14. Symptoms commonly antedated presentation by several years. At least one patient was symptomatic from early infancy. Clinical findings included pes cavus, severe hand and foot weakness and gait abnormalities. One female patient had moderate hearing impairment with no clinical features of neuropathy. One child experienced multiple pathologic fractures. Neurophysiologic testing showed slowing of conduction and axon loss to be far more prominent in the lower extremities. Nerve biopsies showed predominant axonal degeneration with some segmental demyelination and onion bulb formation. Five connexin 32 mutations were identified (Val35Met, His73Fs, Gly159Ser, Ser182Thr and Met34Thr). In five patients mutation analysis was negative.

Conclusion: This is the largest series of childhood CMTX yet described. The clinical phenotype of this condition appears broader than was previously reported, with some cases presenting early and with symptoms being apparent in some carrier females, even in childhood. The pattern of neurophysiologic abnormalities is characteristic and strongly suggestive of the diagnosis of CMTX.