Genetic small fiber sensory neuropathy and channelopathy

Abstract

Genetic neuropathies comprise a range of conditions which can include neuropathy as a predominant feature of the disease or as part of a multisystem disease. Small fiber sensory neuropathy and symptoms have been described in association with sodium channel mutations such as in the SCN9A, SCN10A, and SCN11A genes, which encode Nav1.7, Nav1.8, and Nav1.9 sodium channels, respectively. Erythromelalgia is an autosomal dominant painful condition characterized by redness of the skin and intermittent burning sensation of extremities, triggered by heat or exercise, and was shown to be related to mutations of Nav1.7. Paroxysmal extreme pain disorder (PEPD, first described as familial rectal pain) is an inherited syndrome with paroxysms of rectal, ocular, or submandibular pain with flushing, also linked to gain-of-function mutations of Nav1.7. In addition, SCN9A gene variants have been found in subjects of an idiopathic small fiber neuropathy (SFN) cohort. Predominant involvement of small nerve fibers has been documented in patients with Fabry disease, familial amyloid polyneuropathy (FAP), and Tangier's disease. This chapter focuses on small fiber neuropathies and channelopathies with sensory symptoms, particularly pain, as the sole or primary feature.