Systematic Review and Meta-Analysis: Attention-Deficit/Hyperactivity Disorder Symptoms in Children With Neurofibromatosis Type 1

Objective: This meta-analysis aimed to robustly estimate differences in attention-deficit/hyperactivity disorder (ADHD) symptoms between children and adolescents with and without neurofibromatosis type 1 (NF1).

Method: Systematic literature searches were conducted in Scopus, PsycINFO, Web of Science, PubMed, and ProQuest in September 2022 with a supplemental search conducted in Google Scholar in February 2023. The searches identified 2153 unique articles. Screening identified 114 academic journal articles that assessed parent/caregiver- or teacher-reported ADHD symptoms for children/adolescents with NF1. Two researchers independently screened articles and extracted data. The primary outcome was group differences in ADHD symptoms between children/adolescents with and without NF1 (Hedges' g). Data were analyzed using robust variance estimation and random-effects models.

Results: The meta-analysis included 70 studies (138 effect sizes), involving 3,653 children/adolescents with NF1 (46% female; Mage = 9.69 years, SD = 2.60 years) and 4,895 children/adolescents without NF1 (48% female; Mage = 10.03 years, SD = 3.10 years). According to parent/caregiver reports, children/adolescents with NF1 exhibited more severe inattentive symptoms (g = 1.20; 95% CI [1.06, 1.35]), hyperactive/impulsive symptoms (g = 0.85; 95% CI [0. 68, 1.03]), and combined ADHD symptoms (g = 1.02; 95% CI [0.87, 1.17]) than unaffected controls. Inattentive ADHD symptoms were more elevated than hyperactivity/impulsivity for children/adolescents with NF1. Larger effect sizes for inattention and hyperactivity/impulsivity were associated with older age, lower intelligence quotient (IQ), and parent/caregiver versus teacher reports.

Conclusion: NF1 is a monogenic condition that has strong associations with elevated ADHD symptoms. Findings highlight the importance of early intervention and targeted support for ADHD-related problems in children with NF1.