Govindan Aparna, Fiest Carly, Chou David W, Saade Mia, Gray Mingyang, Cosetti Maura
Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miami, Florida, USA.
Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Otolaryngol Head Neck Surg. 2025 Mar;172(3):811-820. doi: 10.1002/ohn.1060. Epub 2024 Dec 3.
To review the literature on genetics of nonsyndromic microtia and congenital aural atresia (CAA).
Embase, Ovid (Medline), and Web of Science.
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.
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.
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.
综述非综合征性小耳畸形及先天性耳道闭锁（CAA）的遗传学文献。
Embase、Ovid（Medline）及科学网。
检索遵循系统评价与Meta分析的首选报告项目（PRISMA）范围综述指南。纳入研究为讨论非综合征性小耳畸形和/或CAA的遗传学或遗传模式的原创性研究，非综合征性小耳畸形和/或CAA定义为除听力损失外完全孤立存在的小耳畸形和/或CAA。
30项研究符合纳入标准，描述了40个独特基因及1个与非综合征性小耳畸形、CAA或小耳畸形合并CAA相关的易感基因位点（4p15.32 - 4p16.2）。仅描述小耳畸形遗传学的3个被引用最多的基因是HOXA2、MUC6和GSC。单独一篇描述非综合征性CAA的文章将TSHZ1鉴定为候选基因。在18篇描述非综合征性小耳畸形或小耳畸形合并CAA孟德尔遗传的手稿中的194名受试者中，发现49%的个体为常染色体显性遗传，4%为常染色体隐性遗传，5%为X连锁隐性遗传，42%未报告遗传模式。
目前关于小耳畸形和CAA遗传学的文献主要来自综合征患者的基因分析。尽管非综合征患者占临床人群的一半以上，但可用数据仍然有限。了解基因多态性及其与耳鼻喉科医生更容易获得的表型数据的相关性，有望对解剖畸形和听力损失的严重程度进行分类，以指导未来的干预，并提高提供以患者和家庭为中心咨询的能力。
