Genetic basis of Hirschsprung’s disease

  title={Genetic basis of Hirschsprung’s disease},
  author={Paul K.H. Tam and Maria-Mercedes Garcia-Barcel{\'o}},
  journal={Pediatric Surgery International},
Hirschsprung’s disease (HSCR) is a developmental disorder characterized by the absence of ganglion cells in the lower digestive tract. Aganglionosis is attributed to a disorder of the enteric nervous system (ENS) whereby ganglion cells fail to innervate the lower gastrointestinal tract during embryonic development. HSCR is a complex disease that results from the interaction of several genes and manifests with low, sex-dependent penetrance and variability in the length of the aganglionic segment… 
Genetics of Hirschsprung’s Disease
This review will focus on the genes known to be involved in HSCR pathology, how they interact and on how technological advances are being employed to uncover the pathological processes underlying this disease.
Advances in Molecular Genetics of Hirschsprung's Disease
This review discusses the progress that has been made in understanding the molecular genetics of HSCR and summarizes the currently identified genes as well as interactions between pathways and gene‐modifying loci in H SCR.
Genetic Background of Hirschsprung Disease: A Bridge Between Basic Science and Clinical Application
This review focuses on those genes that have been identified as either low penetrant or high penetrant variants that determine the risk of Hirschsprung's disease.
Hirschsprung's disease.
This review aims to draw these strands together to explain the developmental and biological basis of HSCR, and how this knowledge may be used in the future to aid children with H SCR.
Hirschsprung’s Disease and Inflammatory Bowel Disease
The pathophysiological link between HSCR and IBD is not fully understood, but there are similarities between the disorders with respect to altered microbiota and inflammatory responses.
The advances of genetics research on Hirschsprung's disease
This review summaries the current development of the genetics researches on HSCR based on GWASs/EWASs and NGS, focusing on the newly discovered variants and genes, and their potential roles in H SCR pathogenesis.
Comparative proteomics of Hirschsprung's disease.
Genetic interactions and modifier genes in Hirschsprung's disease.
The current knowledge of the genetics underlying Hirschsprung's disease is summarized based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modifier genes.
The Emerging Genetic Landscape of Hirschsprung Disease and Its Potential Clinical Applications
This review summarizes the roadmap of genetic discoveries of HSCR from the earlier family-based linkage analyses to the recent population-based genome-wide analyses coupled with functional genomics, and how these discoveries facilitated the understanding of the genetic architecture of this complex disease and provide the foundation of clinical translation for precision and stratified medicine.
Congenital intestinal stenosis and Hirschsprung’s disease: two extremely rare pathologies in a newborn puppy
This is the first report of congenital intestinal stenosis and Hirschprung’s disease in a newborn puppy and a reduced number of ganglion cells (1–3 cells per ganglions) were found.


Hirschsprung disease, associated syndromes and genetics: a review
Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment, which stands as a model for genetic disorders with complex patterns of inheritance.
The contribution of associated congenital anomalies in understanding Hirschsprung’s disease
  • S. Moore
  • Medicine
    Pediatric Surgery International
  • 2006
The importance of certain flanking genes of critical areas in the final phenotypic expression of HSCR are explored, appearing to arise from the combined cumulative effects of susceptibility loci at critical genes controlling the mechanisms of cell proliferation, differentiation and maturation.
Is there a role for the IHH gene in Hirschsprung's disease?
Investigation of the involvement of the human IHH gene in HSCR revealed seven single nucleotide polymorphisms, six of which were new and should be tested simultaneously to characterize gene–gene interaction.
PMX2B, a new candidate gene for Hirschsprung's disease
The present observation suggests that PMX2B haploinsuffciency might predispose to HSCR, a congenital intestinal malformation of the enteric nervous system.
Role of RET and ko=PHOX2B gene polymorphisms in risk of Hirschsprung’s disease in Chinese population
There is growing evidence indicating that functional single nucleotide polymorphisms (SNPs) of RET could act as low susceptibility factors for Hirschsprung’s disease.
Mutations of the RET proto-oncogene in Hirschsprung's disease
No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest, and it is shown that the mutant genotypes segregate with the disease in HSCR families.
Mapping of a Hirschsprung's disease locus in 3p21
A five-marker haplotype, spanning a 118 kb gene-rich region, was found to be overtransmitted to affected offspring and encompasses three genes involved in neurological phenotypes, and could be used in follow-up studies to finally pinpoint this HSCR locus.
Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease
S segregation analysis suggested an incompletely penetrant dominant inheritance in HSCR families with agan-glionosis extending beyond the sigmoid colon, and mutations of the gene encoding GDNF could either cause or modulate the H SCR phenotype in some cases.
Endothelin-3 Gene Mutations in Isolated and Syndromic Hirschsprung Disease
The present data give further support to the role of the endothelin-signaling pathway in the development of neural crest-derived enteric neurons and suggest the possibility that either recessive or weakly penetrant dominant alleles could occur at the EDN3 locus, depending on the nature of the mutation.
Hirschsprung disease and L1CAM: is the disturbed sex ratio caused by L1CAM mutations?
HSCR is a congenital disorder characterised by an absence of enteric ganglia over various lengths of the bowel and proliferation of nerve fibres in the distal bowel and genetic analysis of HSCR has confirmed the heterogeneity.