Cholesteatoma and family history: An international survey

Abstract

ObjectiveTo explore the relative frequency of a family history of cholesteatoma in patients with known cholesteatoma, and whether bilateral disease or earlier diagnosis is more likely in those with a family history. Associations between cleft lip or palate and bilateral disease and age of diagnosis were also explored.DesignAn online survey of patients with diagnosed cholesteatoma was conducted between October 2017 and April 2019.ParticipantsThe sample consisted of patients recruited from two UK clinics and self‐selected respondents recruited internationally via social media.Main outcome measuresSide of cholesteatoma, whether respondents had any family history of cholesteatoma, age of diagnosis and personal or family history of cleft lip or palate were recorded.ResultsOf 857 respondents, 89 (10.4%) reported a positive family history of cholesteatoma. Respondents with a family history of cholesteatoma were more likely to have bilateral cholesteatoma (P = .001, odds ratio (OR) 2.15, 95% confidence interval (CI) 1.35‐3.43), but there was no difference in the age of diagnosis (P = .23). Those with a history of cleft lip or palate were not more likely to have bilateral disease (P = .051, OR 2.71, CI 1.00‐7.38), and there was no difference in age of diagnosis (P = .11).ConclusionThe relatively high proportion of respondents that reported a family history of cholesteatoma offers supporting evidence of heritability in cholesteatoma. The use of social media to recruit respondents to this survey means that the results cannot be generalised to other populations with cholesteatoma. Further population‐based research is suggested to determine the heritability of cholesteatoma.

A pathogenic deletion in Forkhead Box L1 (FOXL1) identifies the first otosclerosis (OTSC) gene

“…In the NL family, PID III-2 was diagnosed with cholesteatoma at 17 years of age. β-catenin (part of WNT pathway) expression is increased in cholesteatoma cells when compared with normal epithelium cells and we postulate that cholesteatoma, like otosclerosis, may be a result of mutation in FOXL1, given reported cases of familial cholesteatoma, including rare autosomal dominant families (Collins et al 2020;Jennings et al 2018). Industry focus on pharmacologically modulating the Wnt signalling pathway in cancer provides a potential treatment option for otosclerosis and possibly cholesteatoma as well (Zimmerli et al 2017).…”

A Pathogenic Deletion in Forkhead Box L1 (FOXL1) Identifies the First Otosclerosis (OTSC) Gene

“…In the NL family, PID III-2 was diagnosed with cholesteatoma at 17 years of age. β-catenin (part of WNT pathway) expression is increased in cholesteatoma cells when compared with normal epithelium cells and we postulate that cholesteatoma, like otosclerosis, may be a result of mutation in FOXL1, given reported cases of familial cholesteatoma, including rare autosomal dominant families (Collins et al 2020;Jennings et al 2018). Industry focus on pharmacologically modulating the Wnt signalling pathway in cancer provides a potential treatment option for otosclerosis and possibly cholesteatoma as well (Zimmerli et al 2017).…”

Whole exome sequencing study identifies candidate loss of function variants and locus heterogeneity in familial cholesteatoma

“…A clinical observation of familial clustering, and the possibility of a heritable component for cholesteatoma was reported by one of the authors in 2009 (18). A systematic review on the genetics of cholesteatoma identified 35 relevant studies, including case-reports describing segregation of cholesteatoma within families in a pattern consistent with a monogenic, oligogenic, or multifactorial trait (19), and in a recent survey more than ten percent of cholesteatoma patients reported a positive family history (20). Identifying functionally important gene variants associated with disease has potential to uncover the molecular basis of cholesteatoma pathology, and whole exome sequencing (WES) can identify variants in coding DNA that co-segregate with the phenotype.…”

“…A clinical observation of familial clustering, and the possibility of a heritable component for cholesteatoma was reported by one of the authors in 2009 (18). A systematic review on the genetics of cholesteatoma identified 35 relevant studies, including casereports describing segregation of cholesteatoma within families in a pattern consistent with a monogenic, oligogenic, or multifactorial trait (19), and in a recent survey more than ten percent of cholesteatoma patients reported a positive family history (20).…”