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This Article Figures Only Full Text Full Text (PDF) Take the CME quiz CME: Take the course for this article: Volume 71, Number 1, July 1, 2008 Data Supplement Podcast All Versions of this Article: 01.wnl.0000304048.94023.73v1 71/1/14    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bennett, C. L. Articles by Bird, T. D. Search for Related Content PubMed PubMed Citation Articles by Bennett, C. L. Articles by Bird, T. D. Related Collections Peripheral neuropathy Genetic linkage

Late-onset hereditary axonal neuropathies

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.

Address correspondence and reprint requests to Dr Bird, 182-GRECC, VA PSHCS, 1660 S Columbian Way, Seattle, WA 98108 tomnroz{at}u.washington.edu

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.

Abbreviations: AFO = ankle foot orthoses; BAC = bilateral arm crutches; CMAP/SNAP = compound motor and sensory nerve action potentials; CMT = Charcot-Marie-Tooth; CV = conduction velocities; HMSN = hereditary motor and sensory neuropathy; LON = late-onset neuropathy.

e-Pub ahead of print on May 21, 2008, at www.neurology.org.

*These authors contributed equally.

Supplemental data at www.neurology.org

Editorial, page 9

Supported by VA Research Funds, National Institute of Neurological Disorders and Stroke K23, National Center for Research Resources (M01-RR00064), D. Huckabay, and J. Lea.

Disclosure: Dr. Seltzer was an employee of Athena Diagnostics, Inc., at the time of this study. Dr. Chance has received Speaker's Bureau honoraria from Athena Diagnostics, Inc. Dr. Bird has received licensing fees from Athena Diagnostics, Inc.

Received June 20, 2007. Accepted in final form October 31, 2007.