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

Ariane Schmetz¹, Hermann-Josef Lüdecke², Harald Surowy², Sugirtahn Sivalingam², Ange-Line Bruel^{3

4}, Roseline Caumes⁵, Perrine Charles⁶, Nicolas Chatron^{7

8}, Krystyna Chrzanowska⁹, Marta Codina-Solà¹⁰, Cindy Colson⁵, Ivon Cuscó¹⁰, Anne-Sophie Denommé-Pichon^{3

4}, Patrick Edery^{7

11}, Laurence Faivre^{3

12}, Andrew Green¹³, Solveig Heide⁶, Tzung-Chien Hsieh¹⁴, Alexander Hustinx¹⁴, Lotte Kleinendorst¹⁵, Cordula Knopp¹⁶, Florian Kraft¹⁶, Peter M Krawitz¹⁴, Amaia Lasa-Aranzasti¹⁰, Gaetan Lesca^{7

8}, Vanesa López-González¹⁷, Julien Maraval^{3

18}, Cyril Mignot⁶, Teresa Neuhann¹⁹, Christian Netzer^{20

21}, Barbara Oehl-Jaschkowitz²², Florence Petit⁵, Christophe Philippe^{3

4

23}, Renata Posmyk²⁴, Audrey Putoux^{7

11}, André Reis^{25

26}, María José Sánchez-Soler¹⁷, Julia Suh^{16

27}, Tinatin Tkemaladze²⁸, Frédéric Tran Mau Them^{3

4}, André Travessa²⁹, Laura Trujillano¹⁰, Irene Valenzuela¹⁰, Mieke M van Haelst¹⁵, Georgia Vasileiou^{25

26}, Catherine Vincent-Delorme⁵, Mona Walther²⁵, Pablo Verde³⁰, Nuria C Bramswig^#², Dagmar Wieczorek^#^{2

31}

Affiliations

¹ Institute of Human Genetics, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstraße 5, 40225, Düsseldorf, Germany. ariane.schmetz@hhu.de.
² Institute of Human Genetics, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstraße 5, 40225, Düsseldorf, Germany.
³ Inserm UMR1231 Team GAD, University of Burgundy and Franche-Comté, 21000, Dijon, France.
⁴ Functional Unit of Innovative Diagnosis for Rare Diseases, Dijon Bourgogne University Hospital, 21000, Dijon, France.
⁵ CHU Lille, Clinique de Génétique, 59000, Lille, France.
⁶ Assistance Publique-Hôpitaux de Paris, Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
⁷ Service de Génétique, Hospices Civils de Lyon, Bron, France.
⁸ Institute NeuroMyoGène, Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, CNRS UMR 5261-INSERM U1315, Université de Lyon-Université Claude Bernard Lyon 1, Lyon, France.
⁹ Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
¹⁰ Area of Clinical and Molecular Genetics, Vall d'Hebron University Hospital, 08035, Barcelona, Spain.
¹¹ Centre de Recherche en Neurosciences de Lyon, Equipe GENDEV, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Lyon, France.
¹² Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Fédération Hospitalo-Universitaire TRANSLAD et Institut GIMI, Dijon Bourgogne University Hospital, 21000, Dijon, France.
¹³ Department of Clinical Genetics, Children's Health Ireland at Crumlin, and University College Dublin School of Medicine and Medical Science, Dublin, Ireland.
¹⁴ Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
¹⁵ Department of Clinical Genetics, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁶ Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University Hospital, 52074, Aachen, Germany.
¹⁷ Sección Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA), IMIB-Arrixaca, El Palmar, Murcia, Spain.
¹⁸ Centre de Référence Déficiences Intellectuelles de Causes Rares, Dijon Bourgogne University Hospital, 21000, Dijon, France.
¹⁹ Medizinisch Genetisches Zentrum, Munich, Germany.
²⁰ Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²¹ Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²² BIOSCIENTIA MVZ Labor Saar, Praxis Für Humangenetik, Homburg Saar, Germany.
²³ Laboratory of Human Genetics, CHR Metz Thionville, Hôpital Mercy, Metz, France.
²⁴ Department of Clinical Genetics, Medical University in Bialystok, Bialystok, Poland.
²⁵ Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054, Erlangen, Germany.
²⁶ Centre for Rare Diseases Erlangen (ZSEER), 91054, Erlangen, Germany.
²⁷ Centre for Rare Diseases Aachen (ZSEA), 52076, Aachen, Germany.
²⁸ Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia.
²⁹ Medical Genetics Department, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
³⁰ Coordination Centre for Clinical Trials, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
³¹ Center for Rare Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.

^# Contributed equally.

PMID: 38117302
DOI: 10.1007/s00439-023-02622-5

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

Ariane Schmetz et al. Hum Genet. 2024 Jan.

. 2024 Jan;143(1):71-84.

doi: 10.1007/s00439-023-02622-5. Epub 2023 Dec 20.

Authors

Affiliations

¹ Institute of Human Genetics, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstraße 5, 40225, Düsseldorf, Germany. ariane.schmetz@hhu.de.
² Institute of Human Genetics, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstraße 5, 40225, Düsseldorf, Germany.
³ Inserm UMR1231 Team GAD, University of Burgundy and Franche-Comté, 21000, Dijon, France.
⁴ Functional Unit of Innovative Diagnosis for Rare Diseases, Dijon Bourgogne University Hospital, 21000, Dijon, France.
⁵ CHU Lille, Clinique de Génétique, 59000, Lille, France.
⁶ Assistance Publique-Hôpitaux de Paris, Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
⁷ Service de Génétique, Hospices Civils de Lyon, Bron, France.
⁸ Institute NeuroMyoGène, Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, CNRS UMR 5261-INSERM U1315, Université de Lyon-Université Claude Bernard Lyon 1, Lyon, France.
⁹ Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
¹⁰ Area of Clinical and Molecular Genetics, Vall d'Hebron University Hospital, 08035, Barcelona, Spain.
¹¹ Centre de Recherche en Neurosciences de Lyon, Equipe GENDEV, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Lyon, France.
¹² Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Fédération Hospitalo-Universitaire TRANSLAD et Institut GIMI, Dijon Bourgogne University Hospital, 21000, Dijon, France.
¹³ Department of Clinical Genetics, Children's Health Ireland at Crumlin, and University College Dublin School of Medicine and Medical Science, Dublin, Ireland.
¹⁴ Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
¹⁵ Department of Clinical Genetics, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁶ Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University Hospital, 52074, Aachen, Germany.
¹⁷ Sección Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA), IMIB-Arrixaca, El Palmar, Murcia, Spain.
¹⁸ Centre de Référence Déficiences Intellectuelles de Causes Rares, Dijon Bourgogne University Hospital, 21000, Dijon, France.
¹⁹ Medizinisch Genetisches Zentrum, Munich, Germany.
²⁰ Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²¹ Center for Rare Diseases, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
²² BIOSCIENTIA MVZ Labor Saar, Praxis Für Humangenetik, Homburg Saar, Germany.
²³ Laboratory of Human Genetics, CHR Metz Thionville, Hôpital Mercy, Metz, France.
²⁴ Department of Clinical Genetics, Medical University in Bialystok, Bialystok, Poland.
²⁵ Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054, Erlangen, Germany.
²⁶ Centre for Rare Diseases Erlangen (ZSEER), 91054, Erlangen, Germany.
²⁷ Centre for Rare Diseases Aachen (ZSEA), 52076, Aachen, Germany.
²⁸ Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia.
²⁹ Medical Genetics Department, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
³⁰ Coordination Centre for Clinical Trials, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
³¹ Center for Rare Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.

^# Contributed equally.

PMID: 38117302
DOI: 10.1007/s00439-023-02622-5

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

Affiliations

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

Authors

Affiliations

Abstract

References

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Miscellaneous