What this research is about
Ménière’s disease (MD) is a condition affecting the inner ear that causes attacks of vertigo (spinning sensation), fluctuating hearing loss, tinnitus (ringing in the ear), and ear pressure or fullness. Although it’s been known for many years, its cause remains unclear. This review examines what we know about the genetics of MD—how genes may contribute to the disease—and how that knowledge may help us understand who gets it and how to treat it.
Why the genetic approach matters
The authors point out that MD is likely a genetic disorder, and environmental factors can trigger the symptoms (like loud noise, infections, autoimmunity, and allergies). Anatomical differences in the temporal bone also suggest a genetic origin. Because we still manage MD primarily by symptom control (diet, salt restriction, diuretics, surgery in some cases), understanding the underlying genetic causes could lead to better, more specific treatments.
What genetic studies have found so far
- Approximately 1/10 cases are familial. Family studies show that people with a close relative with MD have a higher risk (16-48 times higher) themselves, suggesting genetics plays an important role.
- Rare genetic variations linked to familial MD pathogenesis are primarily found in genes related to the stereocilia links of hair cells in the organ of Corti, including OTOG, TECTA, and MYO7A.
- Around 15% of familial MD is caused by rare mutations in the OTOG gene, and the inheritance is recessive (parents are likely to have no symptoms).
- The most common gene associated with sporadic (non-familial) MD is GJD3, which is found in ~4% of patients. The gene encodes the gap junction protein delta 3, also known as human connexin 31.9 (Cx31.9). A total of 18 MD patients, including 10 familial cases (three unrelated families) and eight sporadic cases, share an identical rare mutation (TGAGT) in the GJD3 coding sequence.
Some studies have found associations with genes involved in immune-system function, fluid regulation in the ear, and inner-ear structure. For example, genes involved in regulating the volume of inner ear fluid or in connecting inner ear cells have been implicated.
Challenges and gaps
- Many studies have small sample sizes, so statistical power is low (it’s easy to get false positives).
- There’s considerable heterogeneity in MD—some patients have mostly vertigo, others mostly hearing loss; some have bilateral disease, some unilateral; some have a clear family history, others don’t. That makes it harder to find consistent genetic patterns.
- Differences in study methods, populations (ethnic background), and diagnostic criteria also limit comparability across studies.
- There is a lack of functional studies—that is, even when a gene variant is associated with MD, we often don’t know how it might lead to disease (what biological mechanism). The review emphasizes that linking gene variants to biological effects in the ear remains an important frontier.
What this means for the future
- The review encourages larger, more collaborative genetic studies across countries, with well-defined MD patient groups and matched controls, to boost the chances of discovering meaningful associations.
- Integrating genetic data with other types of data (epigenomic, transcriptomic) will accelerate mutation discovery.
- Such sub-typing could eventually lead to precision medicine: tailored treatments based on a patient’s genetic and biological profile (rather than “one-size-fits-all”).
- The authors also highlight the need for translational work—taking gene findings and tracing them into lab models to understand mechanisms, which might point to new drug targets or preventive strategies.
Key takeaways
- Familial MD is 10% cases. The causal gene can be identified in 50% of familial patients.
- The most common genes are GJD3, OTOG, MYO7A, and TECTA.
- Many non-familial cases could have a recessive mutation.
Source: Pham MT, Cruz-Granados P, Lopez-Escamez JA. Dissecting the genome in Ménière disease: a review. Res Vestib Sci. 2025;24(3):139-152. doi: 10.21790/rvs.2025.010
This article was reviewed by Jose Antonio Lopez-Escamez, MD, PhD
Additional Resources
A Conversation with the Professor of Meniere’s Disease, by Neil Canham
