Late-onset hereditary axonal neuropathies

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Neurology. 2008 May 21.

Late-onset hereditary axonal neuropathies.

CL, Lawson VH, Brickell KL, Isaacs K, Seltzer W, Lipe HP,

Weiss MD, GT, Flanigan KM, Chance PF, Bird TD.

From the Departments of Pediatrics (C.L.B., P.F.C.), Neurology

(M.D.W., P.F.C., T.D.B.), Medicine (T.D.B.), and Rehabilitation

Medicine (G.T.C.), University of Washington Medical School,

Children's Hospital and Regional Medical Center, Geriatric Research

Education and Clinical Center (T.D.B., H.P.L.), VA Puget Sound Health

Care System, Seattle, WA; Department of Neurology (V.H.W.), Ohio

State University, Columbus; Neurological Foundation of New Zealand

(K.L.B.), Auckland; Walla Walla (K.I.), WA; Athena Diagnostics, Inc.

(W.S.), Worcester, MA; and Departments of Neurology, Pathology, Human

Genetics, and Pediatrics (K.M.F.), University of Utah School of

Medicine, Salt Lake City.

BACKGROUND: Hereditary motor-sensory neuropathy or the Charcot-Marie-

Tooth syndrome is known to represent considerable genetic

heterogeneity. Onset is usually in childhood, adolescence, or young

adulthood. The objective of this study was to define late-onset forms

of the disorder.

METHODS: A clinical and genetic study of families with uniformly late

onset of peripheral neuropathy was performed in a university

neurogenetics setting.

RESULTS: Six families were identified with consistently late onset of

a primarily axonal neuropathy. Median age at symptom onset was 57

years (range 35-85 years) of a mixed motor and sensory neuropathy

with electrophysiologic characteristics of an axonal rather than

demyelinating condition. There was a possible association with

deafness. Two families showed autosomal dominant inheritance whereas

four families had only one affected generation with an excess of

males. An extensive mutation screen of nine genes known to cause

Charcot-Marie-Tooth was negative.

CONCLUSIONS: There are late-onset forms of hereditary axonal

neuropathies. The genetic causes remain unknown and genetic

heterogeneity within this entity is likely.