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

Research output: Contribution to journalArticle


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
Publication statusE-pub ahead of print - Oct 22 2018


Cite this

van der Sluijs, E. P. J., Jansen, S., Vergano, S. A., Adachi-Fukuda, M., Alanay, Y., AlKindy, A., Baban, A., Bayat, A., Beck-Wödl, S., Berry, K., Bijlsma, E. K., Bok, L. A., Brouwer, A. F. J., van der Burgt, I., Campeau, P. M., Canham, N., Chrzanowska, K., Chu, Y. W. Y., Chung, B. H. Y., ... Santen, G. W. E. (2018). The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome. Genetics in Medicine.