Genet Med

. 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

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.

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.