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Age-Specific ADHD and Internalizing/Externalizing Comorbidity in Children with Neurofibromatosis Type 1: A Multi-Site

Dan Liu1, Pamela L Wolters2, Bonita P Klein-Tasman3

  • 1Department of Behavioral Sciences and Social Medicine, College of Medicine, Florida State University, Tallahassee, FL 32306, USA.

Cancers
|February 13, 2026
PubMed

Insights

Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms are consistently linked to internalizing and externalizing problems in children with neurofibromatosis type 1 (NF1). Familial NF1 may increase this risk, highlighting the need for targeted interventions.

Area of Science:

  • Neurodevelopmental Disorders
  • Pediatric Psychology
  • Genetics and Rare Diseases

Background:

  • Neurofibromatosis type 1 (NF1) is a genetic disorder associated with increased risk for neurodevelopmental challenges.
  • Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms are common in children with NF1, often co-occurring with other behavioral issues.
  • Understanding the developmental trajectory of these co-occurring conditions is crucial for effective management.

Purpose of the Study:

  • To investigate the covariation between ADHD symptoms (inattention, hyperactivity/impulsivity) and internalizing/externalizing problems in children with NF1 across development (ages 3-18).
  • To determine if demographic factors (sex, parental education) and NF1-specific factors (inheritance mode) moderate these associations.
  • To identify age-specific patterns in the co-occurrence of ADHD symptoms and behavioral problems in this population.

Main Methods:

  • Analysis of integrated cross-sectional data from 455 children and adolescents with NF1 (685 observations).
  • Assessment of ADHD symptoms and internalizing/externalizing problems using parent-report measures.
  • Application of time-varying effect modeling to examine age-specific associations and moderation analyses for demographic and NF1 factors.

Main Results:

  • ADHD symptoms (inattention, hyperactivity/impulsivity) were significantly associated with increased internalizing and externalizing problems from ages 3-17.
  • The link between inattention and behavioral problems remained consistent across ages, while the hyperactivity/impulsivity-externalizing link was stronger in early childhood.
  • Familial NF1 inheritance mode significantly moderated the inattention-externalizing problem association, indicating a stronger link in this subgroup.

Conclusions:

  • ADHD symptoms are robustly associated with internalizing and externalizing problems throughout childhood and adolescence in individuals with NF1.
  • Familial NF1 is identified as a potential risk factor for a stronger association between inattention and externalizing problems.
  • Further longitudinal and experimental research is warranted to develop integrated interventions, particularly for children with familial NF1.

Keywords:
ADHDage-varying associationsfamilial versus sporadic NF1mental healthneurofibromatosis type 1

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