Genetic Implications on Behavioral Outcomes in Nonsyndromic Sagittal Synostosis
David P. Alper*, Mariana Almeida, Mica C. Williams, Vikram Mookerjee, John Persing, Michael Alperovich
Yale School of Medicine, New Haven, CT
Previous work has identified an association between genetics and neurodevelopmental delays in non-syndromic sagittal craniosynostosis. In this study, we investigated the role of genetic mutations on behavioral outcomes of treated sagittal synostosis.
Parents of children ages 6-18 years old with surgically corrected sagittal synostosis were recruited nationally to complete the Child's Behavioral Checklist (CBCL), Conners-3, Social Responsiveness Scale-2 (SRS-2), and Behavior Rating Inventory of Executive Function-2 (BRIEF-2). CBCL assesses behavioral and emotional function, Conners-3 assesses features of ADHD, SRS-2 assesses features of autism spectrum disorder (ASD), and BRIEF-2 assesses executive function. Multivariate linear regression was used to determine the association of genetic mutations with behavioral scores, while controlling for sociodemographic factors, age at surgery, surgery type, and IQ.
Sixteen of 45 total patients in the study were identified as having mutations after sequencing. There was no significant difference between the genetic and non-genetic mutation groups by sociodemographic factors. A greater proportion of children with genetic mutations 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). In children without these higher rates of genetic mutations, greater age at surgery was associated with worse scores in rule-breaking, aggression and externalizing problems domains, and four out of five ASD domains.
Children with treated nonsyndromic sagittal synostosis and high-risk genotypes had worse behavioral problems in externalizing behaviors and aggression. Within the sub-cohort of patients without genetic mutations, greater age at surgery was an important predictor of worse behavioral outcomes.
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