The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome

Eline P J van der Sluijs, Sandra Jansen, Samantha A Vergano, Miho Adachi-Fukuda, Yasemin Alanay, Adila AlKindy, Anwar Baban, Allan Bayat, Stefanie Beck-Wödl, Katherine Berry, Emilia K Bijlsma, Levinus A Bok, Alwin F J Brouwer, Ineke van der Burgt, Philippe M Campeau, Natalie Canham, Krystyna Chrzanowska, Yoyo W Y Chu, Brain H Y Chung, Karin DahanMarjan De Rademaeker, Anne Destree, Tracy Dudding-Byth, Rachel Earl, Nursel Elcioglu, Ellen R Elias, Christina Fagerberg, Alice Gardham, Blanca Gener, Erica H Gerkes, Ute Grasshoff, Arie van Haeringen, Karin R Heitink, Johanna C Herkert, Nicolette S den Hollander, Denise Horn, David Hunt, Sarina G Kant, Mitsuhiro Kato, Hülya Kayserili, Rogier Kersseboom, Esra Kilic, Malgorzata Krajewska-Walasek, Kylin Lammers, Lone W Laulund, Damien Lederer, Melissa Lees, Vanesa López-González, Saskia Maas, Grazia M S Mancini, Carlo Marcelis, Francisco Martinez, Isabelle Maystadt, Marianne McGuire, Shane McKee, Sarju Mehta, Kay Metcalfe, Jeff Milunsky, Seiji Mizuno, John B Moeschler, Christian Netzer, Charlotte W Ockeloen, Barbara Oehl-Jaschkowitz, Nobuhiko Okamoto, Sharon N M Olminkhof, Carmen Orellana, Laurent Pasquier, Caroline Pottinger, Vera Riehmer, Stephen P Robertson, Maian Roifman, Caroline Rooryck, Fabienne G Ropers, Monica Rosello, Claudia A L Ruivenkamp, Mahmut S Sagiroglu, Suzanne C E H Sallevelt, Amparo Sanchis Calvo, Pelin O Simsek-Kiper, Gabriela Soares, Lucia Solaeche, Fatma Mujgan Sonmez, Miranda Splitt, Duco Steenbeek, Alexander P A Stegmann, Constance T R M Stumpel, Saori Tanabe, Eyyup Uctepe, G Eda Utine, Hermine E Veenstra-Knol, Sunita Venkateswaran, Catheline Vilain, Catherine Vincent-Delorme, Anneke T Vulto-van Silfhout, Patricia Wheeler, Golder N Wilson, Louise C Wilson, Bernd Wollnik, Tomoki Kosho, Dagmar Wieczorek, Evan Eichler, Rolph Pfundt, Bert B A de Vries, Jill Clayton-Smith, Gijs W E Santen

72 Citations (Scopus)


Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features.

Original languageEnglish
JournalGenetics in medicine : official journal of the American College of Medical Genetics
Issue number6
Pages (from-to)1295-1307
Number of pages13
Publication statusPublished - Jun 2019


  • ARID1B
  • bias
  • Coffin–Siris syndrome
  • intellectual disability


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