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Infantile hypertrophic pyloric stenosis—genetics and syndromes

Nature Reviews Gastroenterology & Hepatology volume 9, pages 646–660 (2012)Cite this article

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Abstract

Infantile hypertrophic pyloric stenosis (IHPS) is a common condition in neonates that is characterized by an acquired narrowing of the pylorus. The aetiology of isolated IHPS is still largely unknown. Classic genetic studies have demonstrated an increased risk in families of affected infants. Several genetic studies in groups of individuals with isolated IHPS have identified chromosomal regions linked to the condition; however, these associations could usually not be confirmed in subsequent cohorts, suggesting considerable genetic heterogeneity. IHPS is associated with many clinical syndromes that have known causative mutations. Patients with syndromes associated with IHPS can be considered as having an extreme phenotype of IHPS and studying these patients will be instrumental in finding causes of isolated IHPS. Possible pathways in syndromic IHPS include: (neuro)muscular disorders; connective tissue disorders; metabolic disorders; intracellular signalling pathway disturbances; intercellular communication disturbances; ciliopathies; DNA-repair disturbances; transcription regulation disorders; MAPK-pathway disturbances; lymphatic abnormalities; and environmental factors. Future research should focus on linkage analysis and next-generation molecular techniques in well-defined families with multiple affected members. Studies will have an increased chance of success if detailed phenotyping is applied and if knowledge about the various possible causative pathways is used in evaluating results.

Key Points

  • Genetic factors have an important role in the multifactorial aetiology of infantile hypertrophic pyloric stenosis (IHPS)

  • Family members of affected infants have an increased risk of IHPS

  • Genetic studies have identified different susceptibility loci for IHPS, but these findings could usually not be replicated in subsequent individuals or families, indicating that IHPS has considerable genetic heterogeneity

  • Numerous clinical syndromes are associated with IHPS that result from mutations in genes affecting different pathophysiological pathways

  • Future research should focus on further elucidation of pathophysiological pathways in nonisolated forms of IHPS

  • Next-generation techniques in families and genome-wide association studies in patients with IHPS will probably become successful when detailed phenotyping is applied and if identified pathophysiological pathways are taken into account

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Figure 1: Nitric oxide and its influence in smooth muscle relaxation.

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  1. Department of Pediatric Gastrointestinal Motility and Nutrition, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9,C2-312, Amsterdam, 1105 AZ, The Netherlands

    Babette Peeters & Marc A. Benninga

  2. Department of Pediatrics and Department of Translational Genetics, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9,C2-312, Amsterdam, 1105 AZ, The Netherlands

    Raoul C. M. Hennekam

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Peeters, B., Benninga, M. & Hennekam, R. Infantile hypertrophic pyloric stenosis—genetics and syndromes. Nat Rev Gastroenterol Hepatol 9, 646–660 (2012). https://doi.org/10.1038/nrgastro.2012.133

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