Delineation of the adult phenotype of Coffin–Siris syndrome in 35 individuals

• Published in: Human genetics Vol. 143; no. 1; pp. 71 - 84
• Main Authors: Schmetz, Ariane, Lüdecke, Hermann-Josef, Surowy, Harald, Sivalingam, Sugirtahn, Bruel, Ange-Line, Caumes, Roseline, Charles, Perrine, Chatron, Nicolas, Chrzanowska, Krystyna, Codina-Solà, Marta, Colson, Cindy, Cuscó, Ivon, Denommé-Pichon, Anne-Sophie, Edery, Patrick, Faivre, Laurence, Green, Andrew, Heide, Solveig, Hsieh, Tzung-Chien, Hustinx, Alexander, Kleinendorst, Lotte, Knopp, Cordula, Kraft, Florian, Krawitz, Peter M., Lasa-Aranzasti, Amaia, Lesca, Gaetan, López-González, Vanesa, Maraval, Julien, Mignot, Cyril, Neuhann, Teresa, Netzer, Christian, Oehl-Jaschkowitz, Barbara, Petit, Florence, Philippe, Christophe, Posmyk, Renata, Putoux, Audrey, Reis, André, Sánchez-Soler, María José, Suh, Julia, Tkemaladze, Tinatin, Tran Mau Them, Frédéric, Travessa, André, Trujillano, Laura, Valenzuela, Irene, van Haelst, Mieke M., Vasileiou, Georgia, Vincent-Delorme, Catherine, Walther, Mona, Verde, Pablo, Bramswig, Nuria C., Wieczorek, Dagmar
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2024; Springer Nature B.V; Springer Verlag
• Series: Human Genetics
• Subjects: Adults; Biomedical and Life Sciences; Biomedicine; Coffin-Siris syndrome; Cognitive ability; Gene Function; Hereditary diseases; Human Genetics; Intellectual disabilities; Life Sciences; Metabolic Diseases; Molecular Medicine; Original Investigation; Pediatrics; Phenotypes; Scoliosis; SWI/SNF complex
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-023-02622-5

Coffin–Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA ) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.