FAP and CMT research from Japan

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Research from Rinsho Shinkeigaku. 2003 Nov;43(11):769-74. (just indexed)

Clinical phenotype of Charcot-Marie-Tooth disease (CMT) and familial

amyloid polyneuropathy (FAP) (original article in Japanese)

Sobue G.

Department of Neurology, Nagoya University Graduate School of Medicine.

A nationwide study of CMT and FAP has been performed. In FAP TTR Met30

families with late onset, neuropathy showed male preponderance, low

penetrance, little relationship to endemic foci, sensorimotor symptoms

beginning distally in the lower extremities with disturbance of both

superficial and deep sensation, and relatively mild autonomic symptoms,

consistent with pathological findings. In contrast, families with early

onset

showed higher penetrance, concentration in endemic foci, predominant

loss of superficial sensation, severe autonomic dysfunction.

Demyelinating versus axonal phenotypes are major issues in CMT.

CMT1A duplication caused mainly demyelinating phenotype, while axonal

features were

variably present. In CMT1B, two distinctive phenotypic subgroups were

present: one showed exclusively axonal features; and another was

exclusively demyelinating. CMTX showed intermediate slowing of MCV,

predominantly axonal features, and relatively mild demyelinating

pathology. Differing from CMT1B, these axonal and demyelinating features

were concomitantly present in individual patients in variable extent.

Median nerve MCVs were well maintained independently of age, disease

duration, and severity of clinical and pathologic abnormalities.

Amplitude of CMAPs was correlated significantly with distal muscle

strength, indicating that clinical weakness results from reduced numbers

of functional large axons, not from demyelination.

CMT patients with demyelinating and/or axonal features, together with

FAP patients with axonal feature and scattered distribution, are

supposed to increase according to the

development of genetic diagnosis for hereditary neuropathy that verifies

late-onset, de novo and asymptomatic patients.