Familial clustering and genetic heterogeneity in Meniere's disease

Abstract

The aims of this study were to estimate the prevalence of familial cases in patients with Meniere's disease (MD) and to identify clinical differences between sporadic and familial MD. We recruited 1375 patients with definite MD according to the American Academy of Otolaryngology-Head and Neck Surgery criteria, obtaining the familial history of hearing loss or episodic vertigo by direct interview or a postal survey in 1245 cases in a multicenter study. Familial clustering was estimated by the recurrence risk ratio in siblings (λs ) and offspring (λo ) using intermediate and high prevalence values for MD in European population. A total of 431 patients (34%) reported a familial history of hearing loss or recurrent vertigo and 133 patients had a relative with possible MD. After clinical reevaluation, 93 relatives in 76 families were diagnosed of definite MD (8.4%), including three pairs of monozygotic twins. λs and λo were 16-48 and 4-12, respectively. We observed genetic heterogeneity, but most families had an autosomal dominant inheritance with anticipation. No clinical differences were found between sporadic and familial MD, except for an early onset in familial cases. We may conclude that MD has a strong familial aggregation and that sporadic and familial MDs are clinically identical.

Population-Based Study on the Epidemiology of Ménière's Disease

“…Even if familial aggregation and ethnic diversity have been described in the literature [Ohmen et al, 2013;Requena et al, 2014], we were not in the position to assess these factors since often family history is not recorded and since genetic data are not available within the CPRD. We further could not exclude Cogan syndrome, Tullio phenomenon, or otoliths since no Read codes exist for these conditions either.…”

Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere’s disease

“…15,17 Some of the described families presented co-segregation with migraine and anticipation, 12,25,26 but the two Spanish families that we report here do not show these features. Our study shows that AD-FMD has an incomplete penetrance with variable expressivity and it confirms a clinical heterogeneity in FMD.…”

“…[27][28][29] Third, several relatives in these families presented a partial syndrome with different types of SNHL, including sudden hearing loss (III: 2 in family 2) or pantonal SNHL (II: 2 in family 2) and no vestibular symptoms. These findings observed across different families with MD 12,14,15 suggests that (1) different genes can be involved in the development of the partial or complete phenotype or (2) the interaction of environmental or epigenetic factors can also determine the differences in expressivity within the phenotype. Our findings have started to define two candidate genes associated with FMD and support the hypothesis of genetic heterogeneity in FMD.…”

“…13 Most of the cases of MD are considered sporadic, but familial clustering has been reported. 12,[14][15][16] Familial MD (FMD) is observed in 8-10% of sporadic cases, 17 and FAM136A and DTNA genes have been found in a single family with incomplete penetrance. 18 Although most cases present an autosomal dominant (AD) pattern of inheritance, different patterns have been observed, 14,15 suggesting a genetic heterogeneity in FMD.…”

Pathophysiology of Meniere's Disease

“…While genetic heterogeneity has been observed, most families had an autosomal-dominant inheritance patern with anticipation. No clinical diferences were found between sporadic and familial MD, except for an expected earlier onset in familial cases [10]. Studies have discovered two heterozygous singlenucleotide variants in FAM136A and DTNA genes, both from a Spanish family with three afected cases in consecutive generations, suggestive of autosomal-dominant inheritance [11] with various other gene mutations being explored in diferent familial groups.…”