CMT 1X: Persistent CNS dysfunction in a boy

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J Neurol Sci. 2009 Feb 2. [Epub ahead of print]

Persistent CNS dysfunction in a boy with CMT1X.

Siskind C, Feely SM, Bernes S, Shy ME, Garbern JY.

Department of Neurology, Wayne State University, Detroit, MI, USA.

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.