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

van der Sluijs PJ, Joosten M, Alby C, Attié-Bitach T, Gilmore K, Dubourg C, Fradin M, Wang T, Kurtz-Nelson EC, Ahlers KP, Arts P, Barnett CP, Ashfaq M, Baban A, van den Born M, Borrie S, Busa T, Byrne A, Carriero M, Cesario C, Chong K, Cueto-González AM, Dempsey JC, Diderich KE, Doherty D, Farholt S, Gerkes EH, Gorokhova S, Govaerts LC, Gregersen PA, Hickey SE, Lefebvre M, Mari F, Martinovic J, Northrup H, O'Leary M, Parbhoo K, Patrier S, Popp B, Santos-Simarro F, Stoltenburg C, Thauvin-Robinet C, Thompson E, Vulto-van Silfhout AT, Zahir FR, Scott HS, Earl RK, Eichler EE, Vora NL, Wilnai Y, Giordano JL, Wapner RJ, Rosenfeld JA, Haak MC, Santen GW (2022)

Publication Type: Journal article

Publication year: 2022


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.

Authors with CRIS profile

Involved external institutions

Centre hospitalier universitaire de Rennes / CHU Rennes FR France (FR) University of South Australia AU Australia (AU) Erasmus University Medical Center (MC) NL Netherlands (NL) Eli and Edythe L. Broad Institute of MIT and Harvard US United States (USA) (US) Leiden University Medical Center NL Netherlands (NL) Hôpital Necker-Enfants malades FR France (FR) University of North Carolina at Chapel Hill US United States (USA) (US) University of Washington US United States (USA) (US) Women’s and Children’s Hospital AU Australia (AU) University of Texas Health Science Center at Houston (UTHealth) US United States (USA) (US) Ospedale Pediatrico Bambino Gesu IT Italy (IT) Hôpital de la Timone FR France (FR) Università degli Studi di Siena (UNISI) / University of Siena IT Italy (IT) University of Toronto CA Canada (CA) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES) Rigshospitalet DK Denmark (DK) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen NL Netherlands (NL) Aarhus University Hospital / Aarhus Universitetshospital DK Denmark (DK) Nationwide Children's Hospital US United States (USA) (US) Université de Bourgogne (uB) / University of Burgundy / University of Dijon FR France (FR) Hospital Center University Rouen / Centre hospitalier universitaire de Rouen (CHU) FR France (FR) Hospital Universitario La Paz ES Spain (ES) Charité - Universitätsmedizin Berlin DE Germany (DE) Donders Institute for Brain, Cognition and Behaviour NL Netherlands (NL) University of British Columbia CA Canada (CA) Tel Aviv Sourasky Medical Center / Ichilov Hospital IL Israel (IL) Columbia University Irving Medical Center (CUIMC) US United States (USA) (US) Baylor College of Medicine US United States (USA) (US)

How to cite


van der Sluijs, P.J., Joosten, M., Alby, C., Attié-Bitach, T., Gilmore, K., Dubourg, C.,... Santen, G.W. (2022). Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort. Genetics in Medicine.


van der Sluijs, Pleuntje J., et al. "Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort." Genetics in Medicine (2022).

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