Infantile hypertrophic pyloric stenosis in patients with esophageal atresia.

Autor: Ten Kate CA; Department of Pediatric Surgery and Intensive Care Children, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands., Brouwer RWW; Center for Biomics, Erasmus University Medical Center, Rotterdam, The Netherlands., van Bever Y; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Martens VK; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Brands T; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., van Beelen NWG; Department of Pediatric Surgery and Intensive Care Children, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands., Brooks AS; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Huigh D; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., van der Helm RM; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Eussen BHFMM; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., van IJcken WFJ; Center for Biomics, Erasmus University Medical Center, Rotterdam, The Netherlands., IJsselstijn H; Department of Pediatric Surgery and Intensive Care Children, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands., Tibboel D; Department of Pediatric Surgery and Intensive Care Children, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands., Wijnen RMH; Department of Pediatric Surgery and Intensive Care Children, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands., de Klein A; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Hofstra RMW; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Brosens E; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Birth defects research [Birth Defects Res] 2020 May 15; Vol. 112 (9), pp. 670-687. Date of Electronic Publication: 2020 Apr 16.
DOI: 10.1002/bdr2.1683
Abstrakt: Background: Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes. We hypothesized that defects disturbing foregut morphogenesis are responsible for this combination of malformations.
Methods: We investigated the genetic variation of 15 patients with both EA and IHPS with unaffected parents using exome sequencing and SNP array-based genotyping, and compared the results to mouse transcriptome data of the developing foregut.
Results: We did not identify putatively deleterious de novo mutations or recessive variants. However, we detected rare inherited variants in EA or IHPS disease genes or in genes important in foregut morphogenesis, expressed at the proper developmental time-points. Two pathways were significantly enriched (p < 1 × 10 -5 ): proliferation and differentiation of smooth muscle cells and self-renewal of satellite cells.
Conclusions: None of our findings could fully explain the combination of abnormalities on its own, which makes complex inheritance the most plausible genetic explanation, most likely in combination with mechanical and/or environmental factors. As we did not find one defining monogenetic cause for the EA/IHPS phenotype, the impact of the corrective surgery could should be further investigated.
(© 2020 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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