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Genetics of Hirschsprung’s Disease

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Hirschsprung's Disease and Allied Disorders

Abstract

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 mainly results from the interaction of several genes and manifests with low, sex-dependent penetrance and variability in the length of the aganglionic segment. The genetic complexity observed in HSCR can be conceptually understood in the light of the molecular and cellular events that take place during ENS development. DNA alterations in any of the genes involved in the ENS development may interfere with the colonization process and represent a primary aetiology for HSCR. 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.

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Abbreviations

CDS:

Coding sequences

ENS:

Enteric nervous system

FMTC:

Familiar medullary thyroid carcinoma

HSCR:

Hirschsprung disease, Hirschsprung’s disease, Congenital intestinal aganglionosis, Congenital megacolon

L-HSCR:

Long segment aganglionosis

MEN:

Multiple Endocrine Neoplasia

NCCs:

Neural crest cells

NCDS:

Non-coding regions

PTC:

Papillary thyroid carcinoma

S-HSCR:

Short segment aganglionosis

TCA:

Total colonic aganglionosis

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Acknowledgements

The authors would like to acknowledge the Theme Based Research (TBR) T12C-714/14-R1 grant to PT.

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Authors and Affiliations

  1. Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR China, Hong Kong SAR

    Paul K. H. Tam, Clara S. M. Tang & Maria-Mercè Garcia-Barceló

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  1. Paul K. H. Tam
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  2. Clara S. M. Tang
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  3. Maria-Mercè Garcia-Barceló
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Correspondence to Paul K. H. Tam .

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Editors and Affiliations

  1. National Children’s Research Centre, Our Lady’s Childrens Hospital, University College Dublin, Dublin, Ireland

    Prem Puri

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Tam, P.K.H., Tang, C.S.M., Garcia-Barceló, MM. (2019). Genetics of Hirschsprung’s Disease. In: Puri, P. (eds) Hirschsprung's Disease and Allied Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-15647-3_7

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  • DOI: https://doi.org/10.1007/978-3-030-15647-3_7

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