---
title: "Prevalence of Neuropsychiatric and Seizure Disorders in Neurofibromatosis Type 1: Systematic Revie"
id: "pubmed-42752999"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42752999"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42752999/"
doi: "10.1007/s00415-026-14143-y"
published_at: "2026-09-17T00:00:00.000Z"
evidence_level: "Systematic Review"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Prevalence of Neuropsychiatric and Seizure Disorders in Neurofibromatosis Type 1: Systematic Revie
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42752999
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42752999/)
- **DOI:** [10.1007/s00415-026-14143-y](https://doi.org/10.1007%2Fs00415-026-14143-y)
- **Published At:** 2026-09-17T00:00:00.000Z
- **Evidence Rating:** Systematic Review
## Executive GIST (TL;DR)
- This systematic review and meta-analysis evaluated the prevalence of neuropsychiatric and seizure disorders in patients with **neurofibromatosis type 1 (NF1)** using studies from MEDLINE, Scopus and Web of Science up to April 2026. - Fifty studies met inclusion criteria and random-effects meta-analyses were performed to estimate pooled prevalences with 95% confidence intervals. - Key pooled prevalence estimates in NF1: intellectual disability (ID) 8% (95% CI 6–11, n = 17), autism spectrum disorder (ASD) 11% (95% CI 7–14, n = 17), attention deficit hyperactivity disorder (ADHD) 33% (95% CI 26–40, n = 29), seizures 11% (95% CI 8–14, n = 13), epilepsy 9% (95% CI 6–11, n = 16), depression 13% (95% CI 3–23, n = 11) and anxiety 12% (95% CI 5–20, n = 10). - When genotype was considered, prevalence estimates were higher in the NF1 microdeletion subgroup: ID 41% (95% CI 29–52, n = 2) and ADHD 45% (95% CI 25–65, n = 2). - The authors conclude that **NF1** is associated with a substantial burden of neurodevelopmental, emotional and seizure disorders and support recommendations for routine neuropsychiatric screening in this population. - The review highlights the need for further research incorporating molecular data, especially for NF1 microdeletions, noting that available genotype-specific data were limited. - Conflicts of interest: authors declared none. Ethical approval: no clinical studies or patient data were reported in the manuscript.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain. * 2 Provincial Coordination and Inspection Service, SESCAM, 13001, Ciudad Real, Spain. * 3 Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain. carlos.pascual@uclm.es. * 4 Faculty of Nursing, University of Castilla-La Mancha, 02006, Albacete, Spain. carlos.pascual@uclm.es. * 5 Facultad de Ciencias de La Salud, Universidad Autónoma de Chile, Talca, Chile. * 6 Faculty of Nursing, University of Castilla-La Mancha, 02006, Albacete, Spain. * 7 Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain. * 8 Pediatric service, Complejo Hospitalario Universitario de Albacete (CHUA), SESCAM, 02006, Albacete, Spain. * PMID: **42752999** * DOI: [ 10.1007/s00415-026-14143-y ](https://doi.org/10.1007/s00415-026-14143-y) Item in Clipboard Review # Prevalence of neuropsychiatric and seizure disorders in neurofibromatosis type 1: a systematic review and meta-analysis Elena Moreno-Charco et al. J Neurol. 2026. Show details Display options Display options Format Abstract PubMed PMID J Neurol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Neurol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Neurol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42752999/) . 2026 Sep 17;273(10):603. doi: 10.1007/s00415-026-14143-y. ### Authors [Elena Moreno-Charco](https://pubmed.ncbi.nlm.nih.gov/?term=Moreno-Charco+E&cauthor_id=42752999)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-1 "Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-2 "Provincial Coordination and Inspection Service, SESCAM, 13001, Ciudad Real, Spain."), [Carlos Pascual-Morena](https://pubmed.ncbi.nlm.nih.gov/?term=Pascual-Morena+C&cauthor_id=42752999)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-3 "Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain. carlos.pascual@uclm.es.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-4 "Faculty of Nursing, University of Castilla-La Mancha, 02006, Albacete, Spain. carlos.pascual@uclm.es."), [Celia Álvarez-Bueno](https://pubmed.ncbi.nlm.nih.gov/?term=%C3%81lvarez-Bueno+C&cauthor_id=42752999)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-1 "Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-5 "Facultad de Ciencias de La Salud, Universidad Autónoma de Chile, Talca, Chile."), [Blanca Zuheros-Lara](https://pubmed.ncbi.nlm.nih.gov/?term=Zuheros-Lara+B&cauthor_id=42752999)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-1 "Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain."), [Irene Martínez-García](https://pubmed.ncbi.nlm.nih.gov/?term=Mart%C3%ADnez-Garc%C3%ADa+I&cauthor_id=42752999)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-6 "Faculty of Nursing, University of Castilla-La Mancha, 02006, Albacete, Spain."), [Pilar Martínez-Sánchez](https://pubmed.ncbi.nlm.nih.gov/?term=Mart%C3%ADnez-S%C3%A1nchez+P&cauthor_id=42752999)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-7 "Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-8 "Pediatric service, Complejo Hospitalario Universitario de Albacete \(CHUA\), SESCAM, 02006, Albacete, Spain."), [Miguel Contreras-Molina](https://pubmed.ncbi.nlm.nih.gov/?term=Contreras-Molina+M&cauthor_id=42752999)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-1 "Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain."), [Silvana Patiño-Cardona](https://pubmed.ncbi.nlm.nih.gov/?term=Pati%C3%B1o-Cardona+S&cauthor_id=42752999)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42752999/#short-view-affiliation-1 "Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain.") ### Affiliations * 1 Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain. * 2 Provincial Coordination and Inspection Service, SESCAM, 13001, Ciudad Real, Spain. * 3 Age-ABC Research Group, Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain. carlos.pascual@uclm.es. * 4 Faculty of Nursing, University of Castilla-La Mancha, 02006, Albacete, Spain. carlos.pascual@uclm.es. * 5 Facultad de Ciencias de La Salud, Universidad Autónoma de Chile, Talca, Chile. * 6 Faculty of Nursing, University of Castilla-La Mancha, 02006, Albacete, Spain. * 7 Health and Social Research Center, University of Castilla-La Mancha, 16071, Cuenca, Spain. * 8 Pediatric service, Complejo Hospitalario Universitario de Albacete (CHUA), SESCAM, 02006, Albacete, Spain. * PMID: **42752999** * DOI: [ 10.1007/s00415-026-14143-y ](https://doi.org/10.1007/s00415-026-14143-y) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## 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. **Keywords:** Children; Neurodevelopmental disorders; Neurofibromin; RAS/MAPK; RASopathies; Seizures disorders. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Conflicts of interest: The authors declare that they have no conflict of interest. Ethical approval: The manuscript does not contain clinical studies or patient data. ## References 1. 1. Gutmann DH, Ferner RE, Listernick RH et al (2017) Neurofibromatosis type 1. Nat Rev Dis Primers 3:17004. - [DOI](https://doi.org/10.1038/nrdp.2017.4) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/28230061/) 2. 1. Legius E, Messiaen L, Wolkenstein P et al (2021) Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med 23:1506–1513. - [DOI](https://doi.org/10.1038/s41436-021-01170-5) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34012067/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8354850/) 3. 1. Ratner N, Miller SJ (2015) A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer 15:290–301. - [DOI](https://doi.org/10.1038/nrc3911) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/25877329/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4822336/) 4. 1. Lu Y, Xu M, Chen X et al (2025) Neurofibromatosis type 1: genetic mechanisms and advances in therapeutic innovation. Cancers (Basel) 17:3788. - [DOI](https://doi.org/10.3390/cancers17233788) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/41374990/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/12691366/) 5. 1. Ferner RE, Gutmann DH (2013) Neurofibromatosis type 1 (NF1): diagnosis and management. Handb Clin Neurol 115:939–955. - [DOI](https://doi.org/10.1016/b978-0-444-52902-2.00053-9) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/23931823/) Show all 97 references ## Publication types * Systematic Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Systematic+Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Systematic+Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42752999/) * Meta-Analysis Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Meta-Analysis%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Meta-Analysis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42752999/) * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42752999/) ## MeSH terms * Attention Deficit Disorder with Hyperactivity* / epidemiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Attention+Deficit+Disorder+with+Hyperactivity%2Fepidemiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Attention+Deficit+Disorder+with+Hyperactivity) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42752999/) * Autism Spectrum Disorder* / epidemiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Autism+Spectrum+Disorder%2Fepidemiology%22%5
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