Current genetic evidence does not point to one gene as the cause of familial Ménière’s disease, according to a systematic review of sequencing studies. Instead, the findings suggest a markedly varied genetic picture, with different rare variants reported across a range of genes.
That conclusion matters because Ménière’s disease can appear in families. Familial clustering has been reported in 8% to 10% of cases, which has prompted researchers to look for a genetic contribution. The new review, however, says the available evidence is still provisional and mainly useful for generating hypotheses rather than settling the question.
A scattered set of candidates
The review brought together nine original human genetic studies involving 194 families diagnosed under Bárány Society or AAO–HNS criteria. Across those studies, researchers reported 29 rare variants in 17 genes. The review was designed both to catalogue the sequencing findings and to assess how strong the case was for the genes proposed in the original research.
The review reports 24 of the 29 variants as missense variants. The remaining findings included three nonsense variants and two frameshift deletions.
The original studies labelled 17 variants as pathogenic or likely pathogenic. The review does not establish that these classifications identify causes of Ménière’s disease. Evidence that a variant tracked with the disease within families was limited, and functional validation was not always available.
Why the evidence remains unsettled
The studies did not all use the same methods, the families were small, and information about whether variants segregated with disease was incomplete. Together, those problems greatly weaken causal inference, making it difficult to distinguish a true disease-related gene from a coincidental finding or a variant whose significance is not yet clear.
The biological fit was also uneven. Some candidates, including OTOG, MYO7A, TECTA and DMXL2, have known roles in hearing or auditory function, but the conditions associated with those genes differ markedly from Ménière’s disease. They do not feature the combination of fluctuating hearing loss or episodic vertigo highlighted in the review.
The review was based on a PRISMA-guided search of PubMed and Embase carried out in June 2024. Two reviewers independently screened the studies and extracted the data, reassessed variants using ACMG/AMP guidelines, and evaluated risk of bias with the Newcastle–Ottawa Scale. Even with those safeguards, only nine studies met the inclusion criteria, leaving a relatively narrow and methodologically varied evidence base.
The next tests will need to be larger and more direct
The authors call for larger genome-wide studies to validate candidate genes and clarify the mechanisms involved. They specifically identify knock-in models and patient-specific cochlear or vestibular organoids as possible ways to test those candidates more directly.
For now, the review supports a genetically heterogeneous set of candidates, not a single inherited explanation for familial Ménière’s disease. The current evidence does not support a single monogenic cause, and the authors describe their conclusions as provisional and hypothesis-generating. The paper’s version-of-record date is 20 August 2026. Funding information is not reported in the supplied article text, which is available as a subscription preview.
Paper data and sources
Original title: Genetic contributions to familial Ménière's disease: a systematic review.
Authors: Cassandre Djian, Laurence Jonard, Sandrine Marlin
Journal/Repository: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery
Status: Peer-reviewed
First online: 2026-08-20
DOI: 10.1007/s00405-026-10535-y
Original paper · Full text