Prevalence of neuropsychiatric and seizure disorders in neurofibromatosis type 1: a systematic review and meta-analysis

Abstract

Neurofibromatosis type 1 (NF1) is associated with intellectual disability (ID), autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), emotional and seizure disorders. However, published prevalence estimates vary widely. The aim of this meta-analysis was to estimate the prevalence of ID, ASD, ADHD, epileptic seizures and emotional disorders in NF1. A systematic search was conducted in MEDLINE, Scopus and Web of Science from inception to April 2026. Studies that estimated the proportion of patients with these disorders were included. Where possible, genotype was considered, i.e., NF1 general versus NF1 microdeletions. Random-effects meta-analyses with their 95% confidence intervals (CI) were performed. Fifty studies were included. The prevalence of ID was 8% (95% CI 6–11, n = 17) in NF1 and 41% (95% CI 29–52, n = 2) in NF1 microdeletion; the prevalence of ASD was 11% (95% CI 7–14, n = 17) in NF1; the prevalence of ADHD was 33% (95% CI 26–40, n = 29) in NF1 and 45% (95% CI 25–65, n = 2) in NF1 microdeletion; the prevalence of seizures was 11% (95% CI 8–14, n = 13); the prevalence of epilepsy was 9% (95% CI 6–11, n = 16); and the prevalence of depression and anxiety was 13% (95% CI 3–23, n = 11) and 12% (95% CI 5–20, n = 10). NF1 is associated with neuropsychiatric and seizure disorders, reinforcing existing recommendations for neuropsychiatric screening in this population. Further research incorporating molecular data is also required, particularly in the subgroup with NF1 microdeletions.