Age Trends of Internalizing and Externalizing Problems in Children with Neurofibromatosis Type 1: A Nine-Center Study

Purpose: Children with neurofibromatosis type 1 (NF1) frequently experience internalizing and externalizing problems, but their developmental patterns and predictors remain unclear. This study examined age trends and subgroup differences to inform individualized intervention efforts. Methods: Data from 1,841 children with NF1 (ages 3-18) were combined from nine institutions using integrative data analysis. Internalizing and externalizing problems were assessed with parent-rated Child Behavior Checklist (CBCL; N = 1,087) and Behavior Assessment System for Children (BASC; N = 754), which were analyzed separately. Time-varying effect modeling was used to delineate the age trends of internalizing and externalizing problems for the total samples and for subgroups based on sex, NF1 heritability (familial vs. sporadic), the presence (vs. absence) of plexiform neurofibromas, and attention-deficit/hyperactivity disorder (ADHD) diagnosis. Results: Across CBCL and BASC assessments, children with NF1 consistently exhibited elevated internalizing and externalizing problems compared to the normative means. The between-group gap in internalizing problems significantly widened with age, whereas the gap in externalizing problems remained relatively stable across ages. Age patterns for both types of problems were consistent across sex, NF1 heritability, and status of plexiform neurofibromas. Children with ADHD exhibited significantly higher levels of internalizing and externalizing problems compared to those without ADHD, with the age trends of both problems also differing between the two groups. Conclusions: Internalizing and externalizing problems in NF1 persist during childhood and adolescence and are particularly elevated among children with ADHD. Findings highlight the need for early, sustained, and developmentally tailored interventions, with attention to co-occurring ADHD.