This systematic review and meta-analysis synthesized data from 50 studies to estimate the pooled prevalence of neuropsychiatric conditions and seizure disorders in people with neurofibromatosis type 1 (NF1). Primary pooled estimates reported were: intellectual disability (ID) 8% (95% CI 6–11), autism spectrum disorder (ASD) 11% (95% CI 7–14), attention deficit hyperactivity disorder (ADHD) 33% (95% CI 26–40), seizures 11% (95% CI 8–14), epilepsy 9% (95% CI 6–11), depression 13% (95% CI 3–23) and anxiety 12% (95% CI 5–20). The review also examined genotype where data allowed and reported substantially higher prevalences in the NF1 microdeletion subgroup for ID (41%, 95% CI 29–52) and ADHD (45%, 95% CI 25–65).
The authors conducted a systematic search of MEDLINE, Scopus and Web of Science from database inception through April 2026. Studies were eligible if they estimated the proportion of patients with NF1 who had one or more of the target conditions: intellectual disability, ASD, ADHD, epileptic seizures, or emotional disorders (depression, anxiety). Where available, analyses distinguished between general NF1 cohorts and those with NF1 microdeletions. Random-effects meta-analyses were used to derive pooled prevalence estimates with 95% confidence intervals. The review is reported as a systematic review and meta-analysis and included 50 studies in the pooled analyses.
Pooled analysis across included studies estimated the prevalence of intellectual disability (ID) in NF1 at 8% (95% CI 6–11, n = 17 studies). In the subgroup of patients with NF1 microdeletion, prevalence was higher: 41% (95% CI 29–52, n = 2 studies). These genotype-specific findings indicate a marked increase in ID prevalence in patients with microdeletions compared with the broader NF1 population, although the microdeletion estimate was derived from a limited number of studies.
The pooled prevalence of autism spectrum disorder (ASD) among individuals with NF1 was 11% (95% CI 7–14, n = 17 studies). This result reinforces that ASD occurs at appreciable rates in NF1 cohorts relative to general population expectations, according to the included studies and pooled estimate reported by the authors.
Meta-analysis found a pooled prevalence of attention deficit hyperactivity disorder (ADHD) in NF1 of 33% (95% CI 26–40, n = 29 studies). In the NF1 microdeletion subgroup, the pooled prevalence was reported as 45% (95% CI 25–65, n = 2 studies), indicating a potentially higher risk associated with this genotype. The ADHD estimate in the overall NF1 sample was the highest among neurodevelopmental conditions examined.
The pooled prevalence of seizures in NF1 was 11% (95% CI 8–14, n = 13 studies). When considering diagnosed epilepsy specifically, the pooled prevalence was 9% (95% CI 6–11, n = 16 studies). These results show that both acute seizures and chronic epilepsy are important neurological comorbidities in NF1 populations included in the review.
Emotional disorders were less frequently reported but were included in pooled analyses. The prevalence of depression in NF1 was estimated at 13% (95% CI 3–23, n = 11 studies). The pooled prevalence of anxiety was 12% (95% CI 5–20, n = 10 studies). These estimates indicate a nontrivial burden of mood and anxiety disorders among people with NF1 in the studies reviewed.
The pooled prevalences reported support existing recommendations for routine neuropsychiatric screening in individuals with NF1. High pooled rates for ADHD, as well as elevated rates of ASD, seizures and mood disorders, underscore the need for multidisciplinary assessment and management in NF1 clinics. The markedly higher prevalences seen in the limited microdeletion data suggest genotype-informed risk stratification may be clinically informative where molecular data are available.
The authors emphasize the need for further research that integrates molecular and genotype data to clarify risks across NF1 subgroups. In particular, studies that include larger samples of patients with NF1 microdeletions and that uniformly report neuropsychiatric outcomes would improve precision of subgroup estimates.
While the review pooled data from 50 studies, genotype-specific analyses relied on a small number of studies for the NF1 microdeletion subgroup (n = 2 for the ID and ADHD estimates). The authors note that additional research incorporating molecular characterization is required to refine prevalence estimates and to understand the relationship between NF1 genotype and neuropsychiatric phenotypes. The manuscript reports that the authors declared no conflicts of interest and that the paper did not contain primary clinical studies or patient-level data requiring ethical approval.
Overall, this systematic review and meta-analysis indicates that NF1 is associated with elevated prevalences of neurodevelopmental disorders, emotional disorders and seizure conditions, and it highlights gaps in genotype-informed evidence that warrant further investigation.