Department of Child and Adolescent Health, Aarhus University Hospital, Palle Juul-Jensens Blvd. 99, DK-8200, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Blvd. 11, DK-8200, Aarhus, Denmark.
Clin Genet. 2023 Jul;104(1):22-62. doi: 10.1111/cge.14331. Epub 2023 Mar 27.
The genetic causes underlying incontinence in both children and adults have begun to be unravelled during the last decades. The aim of this scoping review is to synthesize current knowledge on the genetics of childhood and adult urinary and faecal incontinence, identify similarities between different incontinence subgroups, and identify knowledge gaps to aid future research. PRISMA-ScR was used, and 76 studies were included. Early epidemiological family and twin studies suggest high heritability of incontinence. Linkage studies provide evidence for the existence of rare genetic variants; however, these variants have not been identified. Later candidate gene association studies and recent genome-wide association studies provide the first preliminary evidence that common risk variants also play a role. The genetics of incontinence in children and adults has predominantly been studied separately, but this review identifies for the first time the endothelin system as a potential common pathophysiological pathway. Overall, these findings strengthen the hypothesis that genetic variants play a prominent role in the pathogenesis of incontinence. Future research should include hypothesis-free studies of rare and common variants in large well-characterized cohorts with incontinence. Studies should include different age groups and ethnicities and both sexes to fully reveal the genetics of incontinence.
在过去几十年中，儿童和成人失禁的遗传原因已开始被揭示。本综述的目的是综合目前关于儿童和成人尿失禁和粪失禁遗传的知识，确定不同失禁亚组之间的相似之处，并确定知识空白以帮助未来的研究。使用了 PRISMA-ScR，共纳入 76 项研究。早期的流行病学家族和双胞胎研究表明，失禁具有高度遗传性。连锁研究为罕见遗传变异的存在提供了证据；然而，这些变异尚未被识别。后来的候选基因关联研究和最近的全基因组关联研究首次提供了常见风险变异也起作用的初步证据。儿童和成人失禁的遗传学主要是分开研究的，但本综述首次确定内皮素系统是潜在的共同病理生理途径。总的来说，这些发现支持遗传变异在失禁发病机制中起重要作用的假说。未来的研究应包括在具有失禁的大而特征明确的队列中进行罕见和常见变异的无假设研究。研究应包括不同的年龄组和种族以及两性，以充分揭示失禁的遗传学。
