Genetics of vestibular disorders: pathophysiological insights

• Published in: Journal of Neurology Vol. 263; no. Suppl 1; pp. 45 - 53
• Main Authors: Frejo, Lidia, Giegling, Ina, Teggi, Roberto, Lopez-Escamez, Jose A., Rujescu, Dan
• Format: Journal Article Book Review
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016; Springer Nature B.V
• Subjects: Computational Biology; DNA-Binding Proteins; Extracellular Matrix Proteins; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Homeodomain Proteins - genetics; Humans; Medicine; Medicine & Public Health; Mitochondrial Proteins - genetics; Myosins; Neurology; Neuroradiology; Neurosciences; Review; Transcription Factor Brn-3C - genetics; Transcription Factors; Vestibular Diseases - classification; Vestibular Diseases - genetics; Vestibular Diseases - physiopathology; Motion sickness; Vestibular disorders; Meniere disease; Whole exome sequencing; Vestibular migraine
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-015-7988-9

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.