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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Familial Ménière's disease in five generations.

OBJECTIVE: Clinical characterization of a Swedish family followed for five generations. Several members of each generation had Ménière's disease (MD). Possible modes of genetic transmission were assessed. STUDY DESIGN: Retrospective family survey. SETTING: University hospital. Tertiary referral center. PATIENTS: Members of a large family in which several members in each generation were affected by MD. INTERVENTIONS: Hearing levels were assessed, and the patients were asked to complete a questionnaire regarding age at onset, hearing loss, tinnitus, aural fullness, vertigo, and if MD was unilateral or bilateral. Glycerol tests were performed in a few cases. For deceased relatives, information was obtained from patient charts and interviews with relatives. Genetic studies with linkage analysis was performed for the loci DFNA 1, DFNA6/14, DFNA9, and DFNA15. RESULTS: One member of Generation I and, according to patient charts, two members of Generation II could have suffered from MD. In Generations III to V, 9 of 25 members developed inner ear dysfunction. Six of these individuals developed MD that was strictly in accordance with American Academy of Otolaryngology and Head and Neck Surgery, 1995 guidelines criteria, whereas three individuals had unilateral or bilateral hearing impairment, one in combination with benign paroxysmal positioning vertigo, which could represent an incomplete expression of the disease. The mean age at disease onset was 64.5 years in Generation III, 43 years in Generation IV, and 25 years in Generation V. In the genetic studies, none of the regions investigated showed linkage to the disease gene with a significant calculated log of odds ratio (LOD) score above three. CONCLUSION: The pattern of inheritance suggested that familial MD was autosomal dominant and exhibited incomplete expression of inner ear symptoms in some affected members. The decreasing age at onset of disease with succeeding generations could indicate anticipation. None of the hitherto-known DFNA loci, which has phenotypes bearing some resemblance to MD, had haplotypes in common with this large family affected by MD.[1]


  1. Familial Ménière's disease in five generations. Frykholm, C., Larsen, H.C., Dahl, N., Klar, J., Rask-Andersen, H., Friberg, U. Otol. Neurotol. (2006) [Pubmed]
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