{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:05:49Z","timestamp":1792083949394,"version":"4.4.0"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch National Institutes of Health","award":["845006105"],"award-info":[{"award-number":["845006105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Aim: Smith\u2013Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder caused by a 17p11.2 deletion or pathogenic variant in the RAI1 gene. SMS is associated with developmental delay, intellectual disability (ID), and major sleep and behavioral disturbances. To explore how genetic variants may affect intellectual functioning and behavior, we compared intellectual and behavioral phenotypes between individuals with a 17p11.2 deletion and pathogenic RAI1 variant. Method: We reviewed available clinical records from individuals (aged 0\u201345 years) with SMS, ascertained through a Dutch multidisciplinary SMS specialty clinic. Results: We included a total of 66 individuals (n = 47, 71.2% with a 17p11.2 deletion and n = 19, 28.8% with a pathogenic RAI1 variant) for whom data were available on intellectual functioning, severity of ID (n = 53), and behavioral problems assessed with the Child Behavior Checklist (CBCL, n = 39). Median full-scale IQ scores were lower (56.0 vs. 73.5, p = 0.001) and the proportion of individuals with more severe ID was higher (p = 0.01) in the 17p11.2 deletion group. Median total CBCL 6\u201318 scores (73.5 vs. 66.0, p = 0.02) and scores on the sub-scales somatic complaints (68.0 vs. 57.0, p = 0.001), withdrawn\/depressed behavior (69.5 vs. 55.0, p = 0.02), and internalizing behavior (66.0 vs. 55.0, p = 0.002) were higher in the RAI1 group. Conclusion: The results of this study suggest that 17p11.2 deletions are associated with a lower level of intellectual functioning and less internalizing of problems compared to pathogenic RAI1 variants. The findings of this study may contribute to personalized-management strategies in individuals with SMS.<\/jats:p>","DOI":"10.3390\/genes14081514","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:45:02Z","timestamp":1690332302000},"page":"1514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Intellectual and Behavioral Phenotypes of Smith\u2013Magenis Syndrome: Comparisons between Individuals with a 17p11.2 Deletion and Pathogenic RAI1 Variant"],"prefix":"10.3390","volume":"14","author":[{"given":"Cathelijne C.","family":"Linders","sequence":"first","affiliation":[{"name":"Advisium, \u2019s Heeren Loo, 3818 LA Amersfoort, The Netherlands"},{"name":"Department of Genetics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnies M.","family":"van Eeghen","sequence":"additional","affiliation":[{"name":"Advisium, \u2019s Heeren Loo, 3818 LA Amersfoort, The Netherlands"},{"name":"Department of Pediatrics, Emma Children\u2019s Hospital, Amsterdam, University Medical Center, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke R.","family":"Zinkstok","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands"},{"name":"Karakter Child and Adolescent Psychiatry, 6501 BB Nijmegen, The Netherlands"},{"name":"Department of Psychiatry and Brain Center, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jos\u00e9","family":"van den Boogaard","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0593-1539","authenticated-orcid":false,"given":"Erik","family":"Boot","sequence":"additional","affiliation":[{"name":"Advisium, \u2019s Heeren Loo, 3818 LA Amersfoort, The Netherlands"},{"name":"The Dalglish Family 22q Clinic, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Department of Psychiatry & Neuropsychology, Maastricht University, 6200 AB Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/sj.ejhg.5202009","article-title":"Smith-Magenis Syndrome","volume":"16","author":"Elsea","year":"2008","journal-title":"Eur. 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