Genetics of Nonsyndromic Microtia and Congenital Aural Atresia: A Scoping Review.

Objective: To review the literature on genetics of nonsyndromic microtia and congenital aural atresia (CAA).

Data sources: Embase, Ovid (Medline), and Web of Science.

Review methods: The search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews. Included studies were original research studies discussing the genetics or pattern of inheritance of non-syndromic microtia and/or CAA, defined as microtia and/or CAA that was completely isolated except for the presence of hearing loss.

Results: Thirty studies met inclusion criteria, describing 40 unique genes and one susceptibility gene locus (4p15.32-4p16.2) associated with nonsyndromic microtia, CAA, or microtia and CAA. The 3 most cited genes describing microtia genetics alone were HOXA2, MUC6, and GSC. A single article describing nonsyndromic CAA alone identified the TSHZ1 as a candidate gene. Among 194 subjects from 18 manuscripts describing mendelian inheritance for non-syndromic microtia or microtia and CAA, 49% of the individuals were found to have autosomal dominant transmission, 4% had autosomal recessive, 5% had X-linked recessive, and 42% had no reported pattern of inheritance.

Conclusion: Current literature on the genetics of microtia and CAA is largely derived from genetic analysis of syndromic patients. Despite comprising over half of the clinical population, available data on non-syndromic patients remains limited. Understanding genetic polymorphisms and their correlation to phenotypic data more readily available to otolaryngologists offers the prospect of categorizing severity of anatomic malformation and hearing loss to guide future intervention, and improve ability to provide patient- and family-centered counseling.