Genetics of vestibular disorders: pathophysiological insights

Abstract

The two most common vestibular disorders are motion sickness and vestibular migraine, affecting 30 and 1–2 % of the population respectively. Both are related to migraine and show a familial trend. Bilateral vestibular hypofunction is a rare condition, and some of patients also present cerebellar ataxia and neuropathy. We present recent advances in the genetics of vestibular disorders with familial aggregation. The clinical heterogeneity observed in different relatives of the same families suggests a variable penetrance and the interaction of several genes in each family. Some Mendelian sensorineural hearing loss also exhibits vestibular dysfunction, including DFNA9, DFNA11, DFNA15 and DFNA28. However, the most relevant finding during the past years is the familial clustering observed in Meniere’s disease. By using whole exome sequencing and combining bioinformatics tools, novel variants in DTNA and FAM136A genes have been identified in familial Meniere’s disease, and this genomic strategy will facilitate the discovery of the genetic basis of familial vestibular disorders.

Recent Advances in the Understanding of Vestibular Migraine

“…VM is related to migraine and exhibits a familial trend [67]. A genetic deficiency in voltage-gated calcium channels was identified in patients with familial hemiplegic migraine and type II episodic ataxia; these two paroxysmal diseases are characterized by vertigo and migraine as the major symptoms [68].…”

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross‐sectional study with cluster analysis

“…5 Genetic factors may contribute to the development of MD. 6,7 Familial MD has been found in 10% of cases; 8 most of these families have an autosomal dominant pattern of inheritance with incomplete penetrance and variable expressivity. Using exome sequencing, six genes have been involved in familial MD.…”

Clinical Features, Familial History, and Migraine Precursors in Patients With Definite Vestibular Migraine: The VM‐Phenotypes Projects

“…The diagnostic criteria for definite VM are included in the 3rd edition of the International Classification of Headache Disorders (ICHD-III), published in 2013, where it appears in the appendix for new disorders. 7 Familial aggregation has been widely observed in migraine 8 and episodic vertigo, 9 and both disorders may arise from the interplay between genetic predisposition and environmental factors. While different reports have been published on the genetics and familiarity of migraine, the few studies on VM up to the present time have produced inconclusive results.…”