{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:02:13Z","timestamp":1791378133993,"version":"4.3.2"},"reference-count":32,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:sec>\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>Previous work identified an association between genetics and neurodevelopmental delays in patients with nonsyndromic craniosynostosis. The authors investigated the role of genetic mutations on behavioral outcomes of patients with treated sagittal synostosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>METHODS<\/jats:title>\n<jats:p>Parents of children aged 6\u201318 years with surgically corrected sagittal synostosis were recruited to complete the Child Behavioral Checklist (overall behavioral problems), Conners 3rd Edition\u2013Parent (attention-deficit\/hyperactivity disorder), Social Responsiveness Scale 2nd Edition (autism spectrum disorder [ASD]), and Behavior Rating Inventory of Executive Function 2nd Edition (executive function). Genomic analysis was completed, and patients were identified if they had mutations in high probability of loss of function intolerant (pLI) genes (high pLI vs nonhigh pLI). Genetic burden was assessed relative to controls. Multivariate linear regression determined the association of mutations in high pLI genes with behavioral scores, while controlling for sociodemographic factors, age at surgery, surgery type, and IQ.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Sixteen of 45 patients were in the high pLI group. There were no differences between the groups in terms of sociodemographic factors. A greater proportion of children in the high pLI group scored at or above borderline clinical levels for aggression (18.8% vs 0.0%, p = 0.05) and externalizing problems (31.3% vs 3.7%, p = 0.02). Among children in the nonhigh pLI group, older age at surgery was associated with worse scores on the rule-breaking, aggression, and externalizing problems domains and four out of five ASD domains.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>Children with treated nonsyndromic sagittal synostosis and mutations in high pLI genes had worse behavioral problems in externalizing behaviors and aggression, whereas older age at surgery was a significant predictor of worse behavioral outcomes in patients without mutations in high pLI genes.<\/jats:p>\n<\/jats:sec>","DOI":"10.3171\/2024.4.peds23510","type":"journal-article","created":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T02:13:48Z","timestamp":1718417628000},"page":"234-245","source":"Crossref","is-referenced-by-count":3,"title":["The role of genetics on behavioral outcomes in nonsyndromic sagittal synostosis"],"prefix":"10.3171","volume":"34","author":[{"given":"David P.","family":"Alper","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, Yale School of Medicine, New Haven, Connecticut; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana N.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, Yale School of Medicine, New Haven, Connecticut; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin G.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, Yale School of Medicine, New Haven, Connecticut; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny F.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, Yale School of Medicine, New Haven, Connecticut; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Timberlake","sequence":"additional","affiliation":[{"name":"Hansj\u00f6rg Wyss Department of Plastic Surgery, NYU Langone Health, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinesh","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, Yale School of Medicine, New Haven, Connecticut; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Persing","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, Yale School of Medicine, New Haven, Connecticut; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Alperovich","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Plastic Surgery, Yale School of Medicine, New Haven, Connecticut; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"1","key":"b1","series-title":"J Craniofac Surg","first-page":"47","article-title":"An epidemiological study of nonsyndromal craniosynostoses","volume":"22","author":"Kolar JC","year":"2011","unstructured":"Kolar JC. 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