Abstract
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.
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References
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Acknowledgements
We would like to sincerely thank all the individuals and their families for their willingness to participate in this project and their permission to use the data and photographs. We would also like to thank the Association Coffin–Siris France and Coffin–Siris Foundation for their support, as well as Arndt Borkhardt for his involvement as co-supervisor and all other colleagues and caregivers, who helped us to publicize the project. This work is part of the doctoral thesis of A.S. and has been generated within the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA) [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516].
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Study conception and design were performed by AS, NB and DW. All authors contributed to the data collection. AS, NB and H-JL performed data curation and formal analysis. The first draft of the manuscript was written by AS and all authors read, commented and approved the manuscript.
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T.N. is part of the scientific advisory board on LHON genetics Chiesi GmbH. The other authors have no relevant financial or non-financial interests to disclose.
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439_2023_2622_MOESM2_ESM.xlsx
Supplementary Tables: Table S1 Supplementary information about variants from the present study; Table S2 Comprehensive clinical Table; Table S3 Frequencies of clinical characteristics of adult individuals with CSS with confidence intervals; Table S4 Detailed description of health issues (XLSX 73 KB)
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Schmetz, A., Lüdecke, HJ., Surowy, H. et al. Delineation of the adult phenotype of Coffin–Siris syndrome in 35 individuals. Hum. Genet. 143, 71–84 (2024). https://doi.org/10.1007/s00439-023-02622-5
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DOI: https://doi.org/10.1007/s00439-023-02622-5