1. ^*Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
2. ^†Department of Dermatology, CHU Poitiers, Poitiers, France
3. ^‡Pediatric Dermatology Unit, Hôpital Pellegrin-Enfants, Bordeaux, France
4. ^§Department of Medicine, Division of Physical Medicine and Rehabilitation, Dalhousie University, Halifax, NS, Canada

Correspondence: Joost P. H. Drenth, MD, PhD, Department of Medicine, Division of Gastroenterology and Hepatology, University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Email: joostphdrenth@cs.com

Received 19 November 2004; Revised 7 February 2005; Accepted 9 February 2005; Published online 3 June 2005.

Abstract

Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm and painful hands, and/or feet. We previously localized the gene for primary erythermalgia to a 7.94 cM region on chromosome 2q. Recently, Yang et al identified two missense mutations of the sodium channel subunit SCN9A in patients with erythermalgia. The presence of voltage-gated sodium channels in sensory neurons is thought to play a crucial role in several chronic painful neuropathies. We examined four different families and two sporadic cases and detected missense sequence variants in SCN9A to be present in primary erythermalgia patients. A total of five of six mutations were located in highly conserved regions. One family with autosomal dominantly inherited erythermalgia was double heterozygous for two separate SCN9A mutations. These data establish primary erythermalgia as a neuropathic disorder and offers hope for treatment of this incapacitating painful disorder.