title: Autosomal dominant inherited neuropathies with prominent sensory loss and mutilations: a review.
abstract: 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.
authors.affiliation: Institute of Medical Biology and Human Genetics, Karl-Franzens University Graz, Harrachgasse 21/8, A-8010 Graz, Austria. michaela.auergrumbach@kfunigraz.ac.at
authors.forename: Michaela
authors.initials: M
authors.lastname: Auer-Grumbach
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Kristien
authors.initials: K
authors.lastname: Verhoeven
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: Klaus
authors.initials: K
authors.lastname: Wagner
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Garth A
authors.initials: GA
authors.lastname: Nicholson
mesh_terms: D005799:Genes, Dominant; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D012652:Self Mutilation / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D020886:Somatosensory Disorders / Q000209:etiology / Q000235:genetics / Q000503:physiopathology