title: Autosomal dominant hereditary sensory neuropathy with chronic cough and gastro-oesophageal reflux: clinical features in two families linked to chromosome 3p22-p24.
abstract: Autosomal dominant hereditary sensory neuropathy (HSN I) is a clinically and genetically heterogeneous group of disorders, and in some families it is due to mutations in the serine palmitoyltransferase (SPTLC1) gene. We have characterized two families with HSN I associated with cough and gastro-oesophageal reflux (GOR). From a large Australian family, 27 individuals and from a smaller family, 11 individuals provided clinical information and blood for genetic analysis. Affected individuals had an adult onset of paroxysmal cough, GOR and distal sensory loss. Cough could be triggered by noxious odours or by pressure in the external auditory canal (Arnold's ear-cough reflex). Other features included throat clearing, hoarse voice, cough syncope and sensorineural hearing loss. Neurophysiological and pathological studies demonstrated a sensory axonal neuropathy. Gastric emptying studies were normal, and autonomic function and sweat tests were either normal or showed distal hypohidrosis. Cough was likely to be due to a combination of denervation hypersensitivity of the upper airways and oesophagus, and prominent GOR. Most affected individuals were shown on 24 h ambulatory oesophageal pH monitoring to have multiple episodes of GOR, closely temporally associated with coughing. Hoarse voice was probably attributable to acid-induced laryngeal damage, and there was no evidence of vocal cord palsy. No other cause for cough was found on most respiratory or otorhinological studies. Linkage to chromosome 3p22-p24 has been found in both families, with no evidence of linkage to loci for known HSN I, autosomal dominant hereditary motor and sensory neuropathy, hereditary GOR or triple A syndrome. These families represent a genetically novel variant of HSN I, with a distinctive cough owing to involvement of the upper aerodigestive tract.
authors.affiliation: Institute of Clinical Neurosciences, Royal Prince Alfred Hospital and University of Sydney, Australia. pspring@med.usyd.edu.au
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Spring
authors.forename: Cindy
authors.initials: C
authors.lastname: Kok
authors.forename: Garth A
authors.initials: GA
authors.lastname: Nicholson
authors.forename: Alvin J
authors.initials: AJ
authors.lastname: Ing
authors.forename: Judith M
authors.initials: JM
authors.lastname: Spies
authors.forename: Mark L
authors.initials: ML
authors.lastname: Bassett
authors.forename: John
authors.initials: J
authors.lastname: Cameron
authors.forename: Paul
authors.initials: P
authors.lastname: Kerlin
authors.forename: Simon
authors.initials: S
authors.lastname: Bowler
authors.forename: Roger
authors.initials: R
authors.lastname: Tuck
authors.forename: John D
authors.initials: JD
authors.lastname: Pollard
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D002893:Chromosomes, Human, Pair 3; D003371:Cough / Q000209:etiology / Q000235:genetics*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000235:genetics*; D005799:Genes, Dominant; D008040:Genetic Linkage; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000235:genetics; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000150:complications / Q000235:genetics*; D006685:Hoarseness / Q000209:etiology / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013575:Syncope / Q000209:etiology / Q000235:genetics