Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort

Pleuntje J. van der Sluijs, Marieke Joosten, Caroline Alby, Tania Attié-Bitach, Kelly Gilmore, Christele Dubourg, Mélanie Fradin, Tianyun Wang, Evangeline C. Kurtz-Nelson, Kaitlyn P. Ahlers, Peer Arts, Christopher P. Barnett, Myla Ashfaq, Anwar Baban, Myrthe van den Born, Sarah Borrie, Tiffany Busa, Alicia Byrne, Miriam Carriero, Claudia CesarioKaren Chong, Anna Maria Cueto-González, Jennifer C. Dempsey, Karin E.M. Diderich, Dan Doherty, Stense Farholt, Erica H. Gerkes, Svetlana Gorokhova, Lutgarde C.P. Govaerts, Pernille A. Gregersen, Scott E. Hickey, Mathilde Lefebvre, Francesca Mari, Jelena Martinovic, Hope Northrup, Melanie O'Leary, Kareesma Parbhoo, Sophie Patrier, Bernt Popp, Fernando Santos-Simarro, Corinna Stoltenburg, Christel Thauvin-Robinet, Elisabeth Thompson, Anneke T. Vulto-van Silfhout, Farah R. Zahir, Hamish S. Scott, Rachel K. Earl, Evan E. Eichler, Neeta L. Vora, Yael Wilnai, Jessica L. Giordano, Ronald J. Wapner, Jill A. Rosenfeld, Monique C. Haak, Gijs W.E. Santen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Purpose: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes. Methods: Clinical data was collected through an extensive web-based survey. Results: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%). Conclusion: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.

Original languageEnglish
Pages (from-to)1753-1760
Number of pages8
JournalGenetics in Medicine
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 2022

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