Molecular Genetic Analysis of Ménière's Disease

Abstract

Ménière's disease (MD) is an inner ear disease characterised by tinnitus, vertigo and sensorineural hearing loss. The exact aetiology of MD is unknown but it is generally considered as a multifactorial disease. The role of genetic factors in the development of MD has been well documented. Familial clustering of MD has been observed in several studies and the proportion of familial cases is estimated to be 5–23.5%. Single locus on chromosome 12p12.3 has been reported in Swedish MD families. In addition, several inconclusive candidate‐gene analyses have been performed. At the moment, knowledge of genetic factors associated with MD is modest. Molecular genetic study of MD is complicated by genetic and clinical heterogeneity and diagnostic challenges. However, modern genetics may be useful in discovering new pathways associated with the pathophysiology of MD in the future. Key Concepts: The knowledge of genetic factors associated with MD is currently modest. Genetic and clinical heterogeneity, diagnostic challenges, multifactorial origin and late onset of MD create challenges to the molecular genetic analysis of the disease. Family‐based studies may assist to reduce genetic and phenotypic heterogeneity to identify molecular mechanisms or pathways involved in the pathogenesis of MD. Candidate‐gene analysis is an ineffective way to study the genetics of MD and future genetic studies should emphasise the usage of linkage analyses and next‐generation sequencing as well as studying epigenetic pathways. A strong interdisciplinary research environment is needed to successfully study molecular genetics of MD. Combined efforts of highly skilled otologists, geneticists and statisticians are needed to overcome the difficulties in the molecular genetic analyses of MD. To achieve power for genetic studies, a greater number of subjects are needed. This shortcoming may be corrected by an international cooperation between study groups.

Update on Vertigo in Autoimmune Disorders, from Diagnosis to Treatment

“…Although most cases are sporadic, a familial form of the disease has been described, from 2.6% to 23.5% [ 32 ]. Familial MD (FMD) should be considered if at least two family members (first or second degree) fulfill all the criteria of definite or probable MD.…”

Whole‐exome sequencing suggests multiallelic inheritance for childhood‐onset Ménière's disease

“…Patient records of all MD patients who visited the Departments of Otolaryngology in Oulu University hospital (Oulu, Finland) and Kainuu Central Hospital (Kajaani, Finland) during 2005-2010 were studied as previously described to identify familial MD patients (Hietikko et al, 2013a). A male patient diagnosed with childhood-onset MD at the age of 11 was discovered during the study and recruited for further genetic analysis.…”

“…An estimated 5%-15% of MD cases present with a positive family history of MD. Ménière families show autosomal-dominant inheritance with reduced penetrance (Hietikko, Kotimäki, & Mannikko, 2013a). Several genes known to be involved in autoimmunity or fluid homeostasis have been studied as candidate genes of MD, but the studies have been small and the results have not been replicated (Hietikko, Kotimäki, Sorri, & Männikkö, 2013b).…”