Genetics in Medicine Open (Jan 2024)
ARID1B-related disorder in 87 adults: Natural history and self-sustainability
- P.J. van der Sluijs,
- M. Gösgens,
- A.J.M. Dingemans,
- P. Striano,
- A. Riva,
- C. Mignot,
- A. Faudet,
- G. Vasileiou,
- M. Walther,
- S.A. Schrier Vergano,
- M. Alders,
- F.S. Alkuraya,
- I. Alorainy,
- H.S. Alsaif,
- B. Anderlid,
- I. Bache,
- I. van Beek,
- M. Blanluet,
- B.W. van Bon,
- T. Brunet,
- H. Brunner,
- M.L. Carriero,
- P. Charles,
- N. Chatron,
- E. Coccia,
- C. Dubourg,
- R.K. Earl,
- E.E. Eichler,
- L. Faivre,
- N. Foulds,
- C. Graziano,
- A.M. Guerrot,
- M.O. Hashem,
- S. Heide,
- D. Heron,
- S.E. Hickey,
- S.M.J. Hopman,
- A. Kattentidt-Mouravieva,
- J. Kerkhof,
- J.S. Klein Wassink-Ruiter,
- E.C. Kurtz-Nelson,
- K. Kušíková,
- M. Kvarnung,
- F. Lecoquierre,
- G.S. Leszinski,
- L. Loberti,
- P.L. Magoulas,
- F. Mari,
- I. Maystadt,
- G. Merla,
- J.M. Milunsky,
- S. Moortgat,
- G. Nicolas,
- M.O.’ Leary,
- S. Odent,
- J.R. Ozmore,
- K. Parbhoo,
- R. Pfundt,
- M. Piccione,
- A.M. Pinto,
- B. Popp,
- A. Putoux,
- H.L. Rehm,
- A. Reis,
- A. Renieri,
- J.A. Rosenfeld,
- M. Rossi,
- E. Salzano,
- P. Saugier-Veber,
- M. Seri,
- G. Severi,
- F.M. Sonmez,
- G. Strobl-Wildemann,
- K.E. Stuurman,
- E. Uctepe,
- H. Van Esch,
- G. Vitetta,
- B.B.A. de Vries,
- D. Wahl,
- T. Wang,
- P. Zacher,
- K.R. Heitink,
- F.G. Ropers,
- D. Steenbeek,
- T. Rybak,
- G.W.E. Santen
Affiliations
- P.J. van der Sluijs
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
- M. Gösgens
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
- A.J.M. Dingemans
- Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
- P. Striano
- Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
- A. Riva
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy; IRCCS Istituto Giannina Gaslini, Genova, Italy
- C. Mignot
- Service de génétique médicale, APHP Pitié-Salpêtrière, Paris, France
- A. Faudet
- Département de Génétique, Assistance publique - Hôpitaux de Paris Sorbonne Université, Hôpital Pitié-Salpêtrière et Trousseau, Paris, France
- G. Vasileiou
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Centre for Rare Diseases Erlangen (ZSEER), Erlangen, Germany
- M. Walther
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
- S.A. Schrier Vergano
- Children's Hospital of The King's Daughters, Norfolk, VA; Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA
- M. Alders
- Section Clinical Genetics, Department of Human Genetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands
- F.S. Alkuraya
- Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- I. Alorainy
- Department of Radiology and Diagnostic Imaging, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia
- H.S. Alsaif
- Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Centre of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia
- B. Anderlid
- Clinical Genetics Karolinska Universitet Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- I. Bache
- Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- I. van Beek
- Section Clinical Genetics, Department of Human Genetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands
- M. Blanluet
- Service de Génétique Oncologique, Institut Curie, Paris, France
- B.W. van Bon
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
- T. Brunet
- Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Department of Pediatric Neurology and Developmental Medicine and LMU Center for Children with Medical Complexity, Dr. von Hauner Children's Hospital, LMU Hospital, Ludwig-Maximilians-University, D-80337 Munich, Germany
- H. Brunner
- Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
- M.L. Carriero
- Medical Genetics, University of Siena, Siena, Italy
- P. Charles
- Service de génétique médicale, APHP Pitié-Salpêtrière, Paris, France
- N. Chatron
- Service de génétique, Hospices Civils de Lyon ERN ITHACA, INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, Université Claude Bernard Lyon 1, Bron, France; Institut Neuromyogène, Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, Equipe Métabolisme énergétique et développement neuronal, CNRS UMR 5310, INSERM U1217, Université Lyon 1, Lyon, France
- E. Coccia
- Department of Medical and Surgical Science, Postgraduate School of Medical Genetics, Alma Mater Studiorum University of Bologna, Bologna, Italy
- C. Dubourg
- Service de Génétique Moléculaire et Génomique Médicale, CHU de Rennes, Rennes, France; Univ Rennes, CNRS, INSERM, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, ERL U1305, RENNES, France
- R.K. Earl
- Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA
- E.E. Eichler
- Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA; Howard Hughes Medical Institute, University of Washington, School of Medicine, Seattle, WA
- L. Faivre
- Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, CHU Dijon, Dijon, France; Genetics of Developmental Disorders, INSERM - Bourgogne Franche-Comté University, UMR 1231 GAD Team, Dijon, France
- N. Foulds
- Wessex Clinical Genetics Service, University Hospital Southampton, Princess Anne Hospital, Southampton, United Kingdom
- C. Graziano
- Medical Genetics Unit, AUSL Romagna, Cesena, Italy
- A.M. Guerrot
- Department of Genetics and reference Center for Developmental Disorders, Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Rouen, France
- M.O. Hashem
- Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- S. Heide
- Département de Génétique, Assistance publique - Hôpitaux de Paris Sorbonne Université, Hôpital Pitié-Salpêtrière et Trousseau, Paris, France
- D. Heron
- Département de Génétique, Assistance publique - Hôpitaux de Paris Sorbonne Université, Hôpital Pitié-Salpêtrière et Trousseau, Paris, France
- S.E. Hickey
- Division of Genetic & Genomic Medicine, Nationwide Children's Hospital, Columbus, OH; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH
- S.M.J. Hopman
- Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands
- A. Kattentidt-Mouravieva
- Stichting Zuidwester, Middelharnis, the Netherlands
- J. Kerkhof
- Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada
- J.S. Klein Wassink-Ruiter
- Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
- E.C. Kurtz-Nelson
- Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN
- K. Kušíková
- Department of Pediatric Neurology, Faculty of Medicine, Comenius University and National Institute of Children's Diseases, Bratislava, Slovakia
- M. Kvarnung
- Clinical Genetics Karolinska Universitet Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- F. Lecoquierre
- Department of Genetics and reference Center for Developmental Disorders, Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Rouen, France
- G.S. Leszinski
- Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
- L. Loberti
- Medical Genetics, University of Siena, Siena, Italy; Department of Medical Biotechnologies, Med Biotech Hub and Competence Centre, University of Siena, Siena, Italy
- P.L. Magoulas
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
- F. Mari
- Medical Genetics, University of Siena, Siena, Italy
- I. Maystadt
- Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium
- G. Merla
- Department of Molecular Medicine & Medical Biotechnology, University of Naples Federico II, Naples, Italy; Laboratory of Regulatory & Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
- J.M. Milunsky
- Center for Human Genetics Inc, Cambridge, MA
- S. Moortgat
- Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Gosselies, Belgium
- G. Nicolas
- Department of Genetics and reference Center for Developmental Disorders, Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Rouen, France
- M.O.’ Leary
- Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA
- S. Odent
- Univ Rennes, CNRS, INSERM, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, ERL U1305, RENNES, France; Centre de Référence Maladies Rares CLAD-Ouest, ERN-ITHACA, FHU GenOMedS, CHU de Rennes, RENNES, France
- J.R. Ozmore
- Medical Genetics, Dartmouth Hitchcock Medical Center, Lebanon, NH
- K. Parbhoo
- Division of Genetic & Genomic Medicine, Nationwide Children's Hospital, Columbus, OH; The Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, OH
- R. Pfundt
- Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
- M. Piccione
- Medical Genetics Unit, AOOR Villa Sofia-Cervello Hospitals, Palermo, Italy; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
- A.M. Pinto
- Medical Genetics, University of Siena, Siena, Italy
- B. Popp
- Berlin Institute of Health at Charitè, Universitätsklinikum Berlin, Centre of Functional Genomics, Berlin, Germany
- A. Putoux
- Service de génétique, Hospices Civils de Lyon ERN ITHACA, INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, Université Claude Bernard Lyon 1, Bron, France
- H.L. Rehm
- Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA
- A. Reis
- Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Centre for Rare Diseases Erlangen (ZSEER), Erlangen, Germany
- A. Renieri
- Medical Genetics, University of Siena, Siena, Italy; Department of Medical Biotechnologies, Med Biotech Hub and Competence Centre, University of Siena, Siena, Italy
- J.A. Rosenfeld
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Baylor Genetics Laboratories, Houston, TX
- M. Rossi
- Service de génétique, Hospices Civils de Lyon ERN ITHACA, INSERM U1028, CNRS UMR5292, Centre de Recherche en Neurosciences de Lyon, GENDEV Team, Université Claude Bernard Lyon 1, Bron, France
- E. Salzano
- Medical Genetics Unit, AOOR Villa Sofia-Cervello Hospitals, Palermo, Italy
- P. Saugier-Veber
- Department of Genetics and reference Center for Developmental Disorders, Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Rouen, France
- M. Seri
- Department of Medical and Surgical Science, Postgraduate School of Medical Genetics, Alma Mater Studiorum University of Bologna, Bologna, Italy
- G. Severi
- Department of Medical and Surgical Science, Postgraduate School of Medical Genetics, Alma Mater Studiorum University of Bologna, Bologna, Italy
- F.M. Sonmez
- Department of Child Neurology, Karadeniz Technical University Faculty of Medicine, Retired Lecturer, Trabzon, Turkey
- G. Strobl-Wildemann
- MVZ Humangenetik Ulm, Ulm, Germany
- K.E. Stuurman
- Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
- E. Uctepe
- Acıbadem Labmed Ankara Tissue Typing Laboratory, Ankara, Turkey
- H. Van Esch
- Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
- G. Vitetta
- Department of Medical and Surgical Science, Postgraduate School of Medical Genetics, Alma Mater Studiorum University of Bologna, Bologna, Italy
- B.B.A. de Vries
- Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
- D. Wahl
- Department of Clinical Genetics, MVZ Martinsried, Munich, Germany
- T. Wang
- Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA; Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China; Neuroscience Research Institute, Peking University Key Laboratory for Neuroscience, Ministry of Education of China & National Health Commission of China, Beijing, China; Autism Research Center, Peking University Health Science Center, Beijing, China
- P. Zacher
- Epilepsy Center Kleinwachau, Radeberg, Germany
- K.R. Heitink
- Department of Rehabilitation Medicine, Leiden University Medical Center, Leiden, the Netherlands
- F.G. Ropers
- Willem-Alexander Children’s Hospital, department of Pediatrics, Leiden University Medical Center, the Netherlands
- D. Steenbeek
- Department of Rehabilitation Medicine, Maastricht University Medical Center / Adelante Rehabilitation, Maastricht, The Netherlands
- T. Rybak
- 's Heeren Loo Noordwijk, Noordwijk, the Netherlands
- G.W.E. Santen
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; Gijs Santen, Department of Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC Leiden, the Netherlands.
- Journal volume & issue
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Vol. 2
p. 101873
Abstract
Purpose: ARID1B is one of the most frequently mutated genes in intellectual disability cohorts. Thus, far few adult-aged patients with ARID1B-related disorder have been described, which limits our understanding of the disease’s natural history and our ability to counsel patients and their families. Methods: Data on patients aged 18+ years with ARID1B-related disorder were collected through an online questionnaire completed by clinicians and parents. Results: Eighty-seven adult patients with ARID1B were included. Cognitive functioning ranged from borderline to severe intellectual disability. Patients identified through the genetic workup of their child were either mosaic or had a variant in exon 1. New clinical features identified in this population are loss of skill (16/64, 25%) and recurrent patella luxation (12/45, 32%). Self-sustainability data showed that 88% (45/51) could eat independently, and 16% (7/45) could travel alone by public transport. Facial photo analysis showed that patients’ photographs taken at different ages clustered consistently, separate from matched controls. Conclusion: The ARID1B spectrum is broad, and as patients age, there is a significant shift in the medical aspects requiring attention. To address the changing medical needs with increasing age, we have formulated recommendations to promote timely intervention in an attempt to mitigate disease progression.
