Genetics of Hirschsprung’s disease
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Read the article on link.springer.com ↗Article · Feb 2023 · 1 min read
In brief
In brief
This review examines recent genetic discoveries in Hirschsprung's disease through GWAS and next-generation sequencing, revealing complex genetic architecture involving multiple variants with variable penetrance. The authors discuss challenges in translating these findings to clinical risk prediction and propose strategies for advancing precision medicine and novel therapies.
Written by the GCMD Library team from the article.
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.