Anticipation in Menière's disease

Abstract

The aetiology of Menière's disease (MD) remains obscure, but is likely to be multifactorial, one of the factors being a genetic predisposition. Forty-one families with more than one living member with MD were ascertained and affected and normal relations examined. Blood was collected and DNA extracted and stored. In these families the mode of inheritance is autosomal dominant, the penetrance of the mutation being about 60 per cent. Some of the family members exhibit a partial syndrome, vestibular symptoms predominating. Sporadic and familial cases exhibit the same clinical features. The striking finding is the phenomenon of anticipation, whereby with successive generations there is an earlier age of onset and a tendency to more severe manifestation. The inference, considering that the cells which regulate endolymph are of neuroectodermal origin, is that, like other neurodegenerative disorders which show anticipation, MD manifestation is likely to be related to trinucloetide expansion within a gene.

Familial Ménière's disease: clinical and genetic aspects

“…The majority were ascertained in the first few years 28,29 . Most came from private practice, a few from the UK National Health Service (NHS), some from a circular letter to UK ENT surgeons, and a small number from the Ménière's Society, a patient support group.…”

“…Ethical approval for this ongoing work and our subsequent genome search for genes predisposing to The family set -By 1994, from twelve possible families, only eight were suitable for inclusion in a paper also concerned with environmental factors 28 . By 1995 29 >70dB. There is also a functional scale based on patient selection of the best fit of six questions describing increasing incapacity in relation to vertigo-related symptoms.…”

“…Prior papers on our families 2,28,29 We have re-examined all the previously designated cases with partial syndromes and altered them to the most recent AAO-HNS CHE guidelines. The reclassified status of these individuals is not always an accurate reflection of their clinical phenotype.…”

Familiar Meniere's disease restricted to 1.48 Mb on chromosome 12p12.3 by allelic and haplotype association

“…7 Although the majority of cases with MD are sporadic, various studies estimate the frequency of familial cases to be between 5 and 15%. [8][9][10][11][12][13] The inheritance pattern from the analysis of familial cases is likely to be autosomal dominant with a reduced penetrance. Anticipation including both earlier onset and tendency to more severe symptoms in successive generations has also been suggested from a few studies.…”

“…Anticipation including both earlier onset and tendency to more severe symptoms in successive generations has also been suggested from a few studies. 10,11,14 Genetic factors in MD are now widely recognized, but no causative gene variants have been reported despite several suggested candidate genes. Early attempts to identify genetic factors associated with MD include the analysis of the histocompatibility antigens, but no consistent association has been verified.…”