Genetic architecture of Meniere's disease

Meniere's disease (MD) is a complex disorder of the inner ear that causes vertigo attacks, fluctuating sensorineural hearing loss (SNHL), tinnitus and aural fullness. MD has been attributed to an accumulation of endolymph in the cochlear duct. The diagnosis of MD is based on the phenomenological association of clinical symptoms and the demonstration of SNHL during the vertigo attacks. Several evidences support a genetic contribution to MD including differences in the prevalence according to the ethnic background and familial aggregation in European and Asian populations in multiplex families with autosomal dominant inheritance. The genetic underpinnings of MD may include some rare monogenic forms in isolated families and a polygenic contribution in most familial and sporadic cases. So, familial MD has been reported in 6-8% of sporadic cases and several genes have been described in single Familial MD including FAM136A, DTNA, PRKCB, SEMA3D and DPT, suggesting genetic heterogeneity. Multiplex rare missense variants in OTOG gene have been reported in 33% of familial MD, suggesting multiallelic inheritance. Moreover, the genetic landscape of sporadic MD is more complex and it involves multiplex rare variants in several SNHL genes such as GJB2, USH1G, SLC26A4, ESRRB, and CLDN14 and axonal-guidance signalling genes such as NTN4 and NOX3. This review summarizes evidence to support a genetic contribution in MD and the start of deciphering the genetic architecture to design and develop a molecular map of MD.