CMT2B/HSMN/HSN - an international review

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Abstract from Archives of Neurology March 2003

Arch Neurol. 2003;60:329-334.

Autosomal Dominant Inherited Neuropathies With Prominent Sensory Loss

and Mutilations

A Review

a Auer-Grumbach, MD; De Jonghe, MD, PhD; Kristien

Verhoeven, PhD; Timmerman, PhD; Klaus Wagner, PhD; Hans-

Hartung, MD; Garth A. Nicholson, MD, PhD

Hereditary sensory neuropathies (HSNs) are rare disorders characterized

by progressive distal sensory loss, predominantly affecting the lower

limbs. Foot ulcers, severe skin and bone infections, arthropathy, and

amputations are frequent and feared complications. Occasionally,

patients complain of spontaneous shooting or lancinating pain. Autonomic

fibers can be affected to a variable degree. Patients with HSN

can also have severe distal weakness, and some HSN variants have

therefore been classified among the hereditary motor and sensory

neuropathies (HMSNs). Molecular genetic studies of autosomal dominant

inherited neuropathies with prominent sensory loss and ulceromutilating

features have assigned the genetic loci for HMSN type 2B

(Charcot-Marie-Tooth syndrome type 2B) and HSN type 1 to chromosomes

3q13-22 and 9q22.1-22.3, respectively. However, some families with HSN

have been excluded for linkage to these loci, suggesting further genetic

heterogeneity. Recently, disease-causing mutations in the SPTLC1 gene

have been identified in patients with HSN type 1. In this review, we

discuss the hallmark features associated with the distinct genetic

subtypes of autosomal dominant inherited HSN and provide

genotype-phenotype correlations.

From the Institute of Medical Biology and Human Genetics, Karl-Franzens

University Graz, Graz, Austria (Drs Auer-Grumbach and Wagner); the

Flanders Interuniversity Institute for Biotechnology, Born-Bunge

Foundation, University of Antwerp (Drs De Jonghe, Verhoeven, and

Timmerman), and the Division of Neurology, University Hospital Antwerp

(Dr De Jonghe), Antwerp, Belgium; the Department of Neurology,

Heinrich-Heine University, Düsseldorf, Germany (Dr Hartung); and the

Neurobiology Laboratory, Anzac Research Institute, University of Sydney,

Concord Hospital, Concord, Australia (Dr Nicholson).