Objective: X-linked Charcot Marie Tooth disease (CMT1X) is a hereditary demyelinating neuropathy caused by mutations in the GJB1 gene encoding the gap junction protein connexin 32 (Cx32). Some GJB1 mutations have been reported to cause transient clinical CNS dysfunction. We report a boy with persistent CNS abnormalities possibly caused by CMT1X.
Methods: A five year old boy was evaluated by clinical, electrophysiological, MRI and genetic testing.
Results: The patient's early motor milestones were normal to age 5 months. His subsequent course was one of slow improvement punctuated by brief periods of loss of ability to sit between age 5 and 10 months, loss of language between 12 months and 2 years and 1 episode of non-clinically observed resolved left-sided facial weakness. At age 5, he had truncal instability, appendicular ataxia, and dysarthric speech. Cognition was normal. He had mild toe weakness and intrinsic muscle atrophy. MRI evaluation was abnormal. Electrophysiologic testing revealed slowed motor conduction velocities and sensory responses of low amplitude. Genetic workup was normal excepting a novel missense mutation in GJB1, causing a p.54N>H substitution.
Conclusion: The patient has persistent CNS abnormalities characterized by dysarthria and ataxia. These are similar to transient CNS abnormalities reported in patients with CMT1X. These CNS findings may be the direct result of his novel Cx32 mutation.