Persistent CNS Abnormalities in a Boy with CMT1X

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Persistent CNS Abnormalities in a Boy with CMT1X

(ANN April 17, 2008)

Carly E. Siskind, a Feely, Detroit, E. Shy,

Garbern, Detroit, MI

OBJECTIVE: To characterize persistent CNS abnormalities in a male

patient with X-linked Charcot Marie Tooth disease (CMT1X).

BACKGROUND: CMT1X is a hereditary demyelinating neuropathy caused by

mutations in the GJB1 gene encoding the gap junction protein connexin

32 (Cx32). Cx32 is expressed in oligodendrocytes and Schwann cells,

yet clinical manifestations of CMT1X invariably arise from peripheral

neuropathy. Recent studies have demonstrated that some GJB1 mutations

cause transient clinical CNS dysfunction accompanied by diffuse and

symmetric white matter abnormalities, which in some cases followed

potential metabolic stresses. We report a boy with persistent CNS

abnormalities caused by CMT1X.

DESIGN/METHODS: A five year old boy was evaluated by clinical,

electrophysiological, MRI and genetic testing. RESULTS: By 9 months

the patient was unable to sit but was crawling and could pull to

stand. His subsequent course was punctuated by brief periods of loss

of ability to sit between 5 to 10 months of age, development of

dysarthria between 12 months and 2 years of age and 1 episode of non-

clinically observed resolved left-sided facial weakness. At age 5, he

ambulates independently with a walker, but has truncal instability

and appendicular ataxia. Cognitive skills have remained normal

although speech remains dysarthric. He had mild distal toe weakness

and mild intrinsic muscle atrophy. Sensory function was normal. MRI

evaluation revealed deep cerebellar and periventricular cerebral

white matter abnormalities. Nerve conduction velocities are slowed

and sensory responses of low amplitude. A CMT gene panel was tested

which noted only a novel missense mutation in GJB1, predicted to

cause a p.54N>H substitution.

CONCLUSIONS/RELEVANCE: This is the first CMT1X patient reported with

persistent CNS abnormalities. His CNS abnormalities are similar to

transient deficits rarely reported in patients with CMT1X.