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

Genet Med

. 2022 May 17;S1098-3600(22)00727-4. doi: 10.1016/j.gim.2022.04.010. Online ahead of print.

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

Pleuntje J van der Sluijs 1Marieke Joosten 2Caroline Alby 3Tania Attié-Bitach 3Kelly Gilmore 4Christele Dubourg 5Mélanie Fradin 6Tianyun Wang 7Evangeline C Kurtz-Nelson 8Kaitlyn P Ahlers 8Peer Arts 9Christopher P Barnett 10Myla Ashfaq 11Anwar Baban 12Myrthe van den Born 2Sarah Borrie 11Tiffany Busa 13Alicia Byrne 14Miriam Carriero 15Claudia Cesario 16Karen Chong 17Anna Maria Cueto-González 18Jennifer C Dempsey 19Karin E M Diderich 2Dan Doherty 20Stense Farholt 21Erica H Gerkes 22Svetlana Gorokhova 23Lutgarde C P Govaerts 2Pernille A Gregersen 24Scott E Hickey 25Mathilde Lefebvre 26Francesca Mari 15Jelena Martinovic 27Hope Northrup 11Melanie O’Leary 28Kareesma Parbhoo 29Sophie Patrier 30Bernt Popp 31Fernando Santos-Simarro 32Corinna Stoltenburg 33Christel Thauvin-Robinet 34Elisabeth Thompson 10Anneke T Vulto-van Silfhout 35Farah R Zahir 36Hamish S Scott 37Rachel K Earl 8Evan E Eichler 38Neeta L Vora 4Yael Wilnai 39Jessica L Giordano 40Ronald J Wapner 40Jill A Rosenfeld 41Monique C Haak 42Gijs W E Santen 43Affiliations expand


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.

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