Neuropsychiatric phenotypes in children with Noonan syndrome

AimWe investigated neuropsychiatric outcomes in children with Noonan syndrome and addressed limitations in previous research with a focus on prepubertal children, comparison to typically developing children, comprehensive neuropsychiatric evaluation, and controlling for overall cognitive abilities. MethodForty-five children with Noonan syndrome (mean = 8 years 6 months, SD = 2 years 2 months; 29 females) and 40 typically developing children (mean = 8 years 9 months, SD = 2 years; 22 females) were evaluated with objective, parent-report, and psychiatric interview measures. ResultsChildren with Noonan syndrome demonstrated elevated symptoms across attention-deficit/hyperactivity disorder (ADHD) (attention, hyperactivity, and inhibition), autism spectrum disorder (ASD) (maintaining social relationships, behavioral rigidity, and sensory sensitivity), and oppositional defiant disorder (ODD) (aggression) symptom clusters relative to typically developing children (all p < 0.05). Group differences in nearly all parent-report measures were significant after accounting for variations in intellectual functioning, suggesting that increased neurodevelopmental symptoms are not simply driven by overall intelligence. Twenty out of 42 children with Noonan syndrome met criteria for ADHD, eight out of 42 for ODD, and 11 out of 43 demonstrated clinically significant symptoms seen in children with ASD. InterpretationChildren with Noonan syndrome are at increased risk for a range of ADHD, ASD, and ODD associated symptoms. A dimensional approach reveals significant ASD symptoms in Noonan syndrome that do not emerge when using the currently accepted categorical diagnostic approach.

Automated summary

This study investigated neuropsychiatric outcomes in children with Noonan syndrome and addressed limitations in previous research by focusing on prepubertal children, comparison to typically developing children, comprehensive neuropsychiatric evaluation, and controlling for overall cognitive abilities. Results showed that children with Noonan syndrome had elevated symptoms across ADHD, ASD, and ODD symptom clusters, and the group differences remained significant even after accounting for variations in intellectual functioning. The study revealed that Noonan syndrome children are at increased risk for a range of ADHD, ASD, and ODD associated symptoms, and a dimensional approach is important in assessing ASD symptoms in Noonan syndrome.