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

Sluijs, P.J. van der; Jansen, S.; Vergano, S.A.; Adachi-Fukuda, M.; Alanay, Y.; AlKindy, A.; ... ; Santen, G.W.E. (2019)

Article / Letter to editor

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 (ARID1BCSS) 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 webbased 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 ARID1BID 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.

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

• All authors: Sluijs, P.J. van der; Jansen, S.; Vergano, S.A.; Adachi-Fukuda, M.; Alanay, Y.; AlKindy, A.; Baban, A.; Bayat, A.; Beck-Wodl, S.; Berry, K.; Bijlsma, E.K.; Bok, L.A.; Brouwer, A.F.J.; Burgt, I. van der; Campeau, P.M.; Canham, N.; Chrzanowska, K.; Chu, Y.W.Y.; Chung, B.H.Y.; Dahan, K.; Rademaeker, M. de; Destree, A.; Dudding-Byth, T.; Earl, R.; Elcioglu, N.; Elias, E.R.; Fagerberg, C.; Gardham, A.; Gener, B.; Gerkes, E.H.; Grasshoff, U.; Haeringen, A. van; Heitink, K.R.; Herkert, J.C.; Hollander, N.S. den; Horn, D.; Hunt, D.; Kant, S.G.; Kato, M.; Kayserili, H.; Kersseboom, R.; Kilic, E.; Krajewska-Walasek, M.; Lammers, K.; Laulund, L.W.; Lederer, D.; Lees, M.; Lopez-Gonzalez, V.; Maas, S.; Mancini, G.M.S.; Marcelis, C.; Martinez, F.; Maystadt, I.; McGuire, M.; McKee, S.; Mehta, S.; Metcalfe, K.; Milunsky, J.; Mizuno, S.; Moeschler, J.B.; Netzer, C.; Ockeloen, C.W.; Oehl-Jaschkowitz, B.; Okamoto, N.; Olminkhof, S.N.M.; Orellana, C.; Pasquier, L.; Pottinger, C.; Riehmer, V.; Robertson, S.P.; Roifman, M.; Rooryck, C.; Ropers, F.G.; Rosello, M.; Ruivenkamp, C.A.L.; Sagiroglu, M.S.; Sallevelt, S.C.E.H.; Calvo, A.S.; Simsek-Kiper, P.O.; Soares, G.; Solaeche, L.; Sonmez, F.M.; Splitt, M.; Steenbeek, D.; Stegmann, A.P.A.; Stumpel, C.T.R.M.; Tanabe, S.; Uctepe, E.; Utine, G.E.; Veenstra-Knol, H.E.; Venkateswaran, S.; Vilain, C.; Vincent-Delorme, C.; Vulto-van Silfhout, A.T.; Wheeler, P.; Wilson, G.N.; Wilson, L.C.; Wollnik, B.; Kosho, T.; Wieczorek, D.; Eichler, E.; Pfundt, R.; Vries, B.B.A. de; Clayton-Smith, J.; Santen, G.W.E.
• Date: 2019-06-01
• Journal: Genetics in Medicine
• Volume: 21
• Issue: 6
• Pages: 1295 - 1307
• DOI: doi:10.1038/s41436-018-0330-z