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01-12-2023 | Review Article

Genetics of Hirschsprung’s disease

Authors: Clara Sze-man Tang, Anwarul Karim, Yuanxin Zhong, Patrick Ho-yu Chung, Paul Kwong-hang Tam

Published in: Pediatric Surgery International | Issue 1/2023

Abstract

Hirschsprung’s disease (HSCR) is a classical model of enteric neuropathy, occurring in approximately 2–2.8 in 10,000 newborns. It is the commonest form of congenital bowel obstruction and is characterized by the absence of enteric ganglia in distal colon. Recent advances in genome-wide association analysis (GWAS) and next generation sequencing (NGS) studies have led to the discovery of a number of new HSCR candidate genes, thereby providing new insights into the genetic architecture and molecular mechanisms of the disease. Altogether, these findings indicated that genetic heterogeneity, variable penetrance and expressivity, and genetic interaction are the pervasive characteristics of HSCR genetics. In this review, we will provide an update on the genetic landscape of HSCR and discuss how the common and rare variants may act together to modulate the phenotypic manifestation. Translating the genetic findings to genetic risk prediction and to optimize clinical outcomes are undoubtedly the ultimate goals for genetic studies on HSCR. From this perspective, we will further discuss the major obstacles in the clinical translation of these latest genetic findings. Lastly, new measures to address these clinical challenges are suggested to advance precision medicine and to develop novel alternative therapies.

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Title: Genetics of Hirschsprung’s disease
Authors: Clara Sze-man Tang
Anwarul Karim
Yuanxin Zhong
Patrick Ho-yu Chung
Paul Kwong-hang Tam
Publication date: 01-12-2023
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 1/2023
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-022-05358-x

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Genetics of Hirschsprung’s disease

Abstract

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Abstract

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