Type X Disability research - from Switzerland

March 7, 2003

Abstract from J Neurol Sci 2003 Mar 15;207(1-2):77-86

Phenotypic expression of a Pro 87 to Leu mutation in the onnexin 32 gene

in a large Swiss family with Charcot-Marie-Tooth neuropathy.

Kuntzer T, Dunand M, Schorderet DF, Vallat JM, Hahn AF, Bogousslavsky J.

Service de Neurologie, Centre Hospitalier Universitaire Vaudois, BH

7/306, 1011, Lausanne, Switzerland

BACKGROUND: The clinical manifestations of CMTX have been well described

but the natural history has not yet been studied in detail. We studied

phenotype variability in a family with a Pro 87 to Leu mutation of the

connexin 32 (Cx32) gene.

METHODS: A total of 32 family members, of which 19 patients were

affected, underwent clinical, electrophysiological, and genetic studies.

RESULTS: Onset was in the second decade. Clinical features were similar

in both sexes when quantitative scores were compared, but more males had

a steppage gait and skeletal deformities. All adult patients had a

predominant involvement of the thenar muscles. The median values of

nerve conduction velocities (NCVs) were not statistically different in

men and in women. The correlation coefficients were low between motor

NCVs within the same extremities, indicating nonuniform slowing between

nerves, the ulnar nerve being the least affected. When disability was

rated, a strong correlation was seen in male patients between severity

of motor axonal loss and duration of the disease. The main pathological

features were axonal loss, clusters of regenerating fibers and paranodal

demyelination, the hallmark of a Schwann cell pathology.

CONCLUSIONS: Our data support the hypothesis that clinical disability in

CMTX is caused by loss of large myelinated axons in men. Furthermore,

this study shows that the nerves are not uniformly affected in terms of

axonal loss. Preventing axonal degeneration and promoting axonal

regeneration in the most affected nerves might be the best therapeutic

approaches to ameliorate disability in CMTX.

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