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Congenital Anomalies and Genetic Associations in Hirschsprung’s Disease

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Hirschsprung's Disease and Allied Disorders

Abstract

Hirschsprung’s disease is a complex congenital disorder mostly of genetic origin, which from a molecular perspective appears to result from disruption of normal signalling during development of enteric nerve cells, resulting in aganglionosis of the distal bowel. It is a frequent cause of neonatal intestinal obstruction and beyond.

It occurs as an isolated phenotype in 70% but is not infrequently associated with congenital abnormalities (5–32%) and syndromic phenotypes. These abnormalities have been linked to distinct genetic sites, indicating underlying genetic associations of the disease and probable gene-gene interaction in its pathogenesis.

This review looks at the prevalence, congenital associations and possible genetic factors influencing the development of congenital anomalies. In addition, possible tumour linkages and other autonomic nervous system disturbances are investigated. The combined effects of a number of susceptibility loci at critical genes controlling the mechanisms of cell proliferation, differentiation and maturation as well as the influence of potential ‘modifying’ associations and modifying genetic factors on the final phenotypic expression of HSCR are also explored.

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  1. Division of Pediatric Surgery, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, South Africa

    Samuel William Moore

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

    Prem Puri

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Moore, S.W. (2019). Congenital Anomalies and Genetic Associations in 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_11

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