Neuropathy, Hereditary Sensory And Autonomic, Type I, With Cough And Gastroesophageal Reflux

Description

The hereditary sensory and autonomic neuropathies (HSAN), which are also referred to as hereditary sensory neuropathies (HSN) in the absence of significant autonomic features, are a genetically and clinically heterogeneous group of disorders associated with sensory dysfunction. For a discussion of genetic heterogeneity of HSAN, see HSAN1A (162400).

Clinical Features

HSN1 with cough and gastroesophageal reflux (GER) was described by Spring et al. (2002). The first symptoms of HSN1 with cough and GER were sometimes an unexplained chronic cough, which could progress to cough syncope. Monitoring of esophageal pH for 24 hours showed the cough to be temporally associated with GER and impaired laryngeal sensation. The disorder usually presented in adult life, with either cough or GER symptoms. The cough may occur between the second and the fourth decades. Sensory loss began in the feet and legs between the third and fifth decades. Achilles tendon reflexes were decreased in some individuals, and nerve conduction velocity studies showed an axonal neuropathy with absent or reduced sensory nerve action potentials. Nerve biopsy showed loss of unmyelinated and myelinated axons.

Spring et al. (2005) reported detailed clinical features of the 2 unrelated affected families studied by Kok et al. (2003). Affected individuals had onset in early adulthood of paroxysmal cough and frequent throat clearing associated with gastroesophageal reflux, with later onset of an axonal neuropathy with distal sensory impairment of the upper and lower limb. The cough was triggered by noxious odors or by pressure in the external auditory canal and could be severe. Variable features included bilateral sensorineural hearing loss, lancinating pains, alacrima, and impotence.

Mapping

Kok et al. (2003) identified 2 families with HSN1 with cough and GER. One, a 3-generation Australian family, was large enough for linkage studies. Male-to-male transmission indicated autosomal dominant inheritance. The second unrelated family with 9 at-risk family members was large enough for haplotype studies. Genome screen showed linkage to 3p24-p22, with a lod score of 3.51 at marker D3S2338 and a recombination fraction of 0.0. The 2 families did not share a common disease haplotype.