. 2022 May 17;S1098-3600(22)00727-4. doi: 10.1016/j.gim.2022.04.010. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/35579625/
Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort
Pleuntje J van der Sluijs 1, Marieke Joosten 2, Caroline Alby 3, Tania Attié-Bitach 3, Kelly Gilmore 4, Christele Dubourg 5, Mélanie Fradin 6, Tianyun Wang 7, Evangeline C Kurtz-Nelson 8, Kaitlyn P Ahlers 8, Peer Arts 9, Christopher P Barnett 10, Myla Ashfaq 11, Anwar Baban 12, Myrthe van den Born 2, Sarah Borrie 11, Tiffany Busa 13, Alicia Byrne 14, Miriam Carriero 15, Claudia Cesario 16, Karen Chong 17, Anna Maria Cueto-González 18, Jennifer C Dempsey 19, Karin E M Diderich 2, Dan Doherty 20, Stense Farholt 21, Erica H Gerkes 22, Svetlana Gorokhova 23, Lutgarde C P Govaerts 2, Pernille A Gregersen 24, Scott E Hickey 25, Mathilde Lefebvre 26, Francesca Mari 15, Jelena Martinovic 27, Hope Northrup 11, Melanie O’Leary 28, Kareesma Parbhoo 29, Sophie Patrier 30, Bernt Popp 31, Fernando Santos-Simarro 32, Corinna Stoltenburg 33, Christel Thauvin-Robinet 34, Elisabeth Thompson 10, Anneke T Vulto-van Silfhout 35, Farah R Zahir 36, Hamish S Scott 37, Rachel K Earl 8, Evan E Eichler 38, Neeta L Vora 4, Yael Wilnai 39, Jessica L Giordano 40, Ronald J Wapner 40, Jill A Rosenfeld 41, Monique C Haak 42, Gijs W E Santen 43Affiliations expand
- PMID: 35579625
- DOI: 10.1016/j.gim.2022.04.010
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.
Keywords: ARID1A; ARID1B BAFopathy; BAF-complex; Fetal; SMARCA4; SMARCB1.
Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.