Clin Surg | Volume 2, Issue 1 | Review Article | Open Access

The Evolving Genetic Landscape of Hirschprung Disease: An Update and Review

Amit Kumar Yadav* and Gaurav Chopra

Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India

*Correspondance to: Amit Kumar Yadav 

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Hirschsprung Disease (HD) is a developmental disorder characterized by the complete absence of ganglion cells in the distal gastrointestinal tract. It is the most common cause of functional intestinal obstruction in neonates and children. The aganglionosis is believed to be either due to failure of neural crest cells to migrate, proliferate, differentiate or survive during gut development in the embryonic stage. The incidence of HD is estimated at 1/5000 live births and shows a male predominance. It is usually sporadic, although it can be familial and may be inherited as autosomal dominant or autosomal recessive. In 70% of cases, HD occurs as an isolated trait and in the other 30% it is associated with other congenital malformation syndromes. HD has a complex multifactorial etiology, and genetic factors play a key role in its pathogenesis. Several gene loci appear to be involved. Many of these have been identified by conducting Genome Wide Association (GWAS) studies and recently by Next Generation Sequencing (NGS). These genes encode for receptors, ligands (especially those participating in the RET, EDNRB and Semaphorin signaling pathways), transcriptional factors (PHOX2B & SOX10). These genes are involved in the neural crest cell development and migration that give rise to ganglion cells. Overall, the RET proto-oncogene is considered the major disease causing gene in HD. A greater understanding of the genetic landscape of this disease might pave way for genetic counseling, prenatal and preimplantation diagnosis in the management of HD.


Hirschprung disease; Genetics; RET; Genome wide association studies (GWAS); Next generation sequencing (NGS); Semaphorins


Yadav AK, Chopra G. The Evolving Genetic Landscape of Hirschprung Disease: An Update and Review. Clin Surg. 2017; 2: 1672.

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