Neurofibromatosis type 1

By Laura Boyd and Agata Buczak

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic tumor‑predisposition disorder caused by pathogenic variants in the NF1 tumor suppressor gene, affecting approximately 1 in 3,000 people worldwide, with a global pooled prevalence estimate of 1 in 3,164.^1,2

NF1 is characterized by marked clinical heterogeneity, with manifestations ranging from mild cutaneous findings to complex, multisystem involvement affecting the eyes, bones, vasculature, lungs, and the nervous, gastrointestinal, and endocrine systems.³ Clinical features may evolve, necessitating lifelong monitoring.³

What causes NF1?

NF1 results from loss‑of‑function mutations in the NF1 gene, leading to reduced neurofibromin activity and RAS activation.⁴ This promotes abnormal cell growth and increases tumor risk. Around half of cases are inherited from an affected parent; the remainder arise from de novo mutations.⁴

What are the symptoms of NF1?

NF1 symptoms vary in type and severity. Common features include:⁵

• Café‑au‑lait macules
• Axillary or inguinal freckling
• Cutaneous neurofibromas
• Iris Lisch nodules

Severe manifestations may include:⁵

• Plexiform neurofibromas (PN) causing pain or functional impairment
• Learning difficulties and neurocognitive impairment
• Skeletal abnormalities, such as scoliosis
• Optic pathway gliomas
• Vasculopathy

How is NF1 diagnosed?

Diagnosis of NF1 is primarily clinical and based on internationally recognized diagnostic criteria.⁶ Genetic testing for NF1 variants may support diagnosis, particularly in young children, atypical presentations, or suspected mosaic disease.¹

Imaging, including MRI, is used selectively to assess internal tumors or disease‑related complications.¹

What are the treatment options for NF1?

There is no cure for NF1, and management is individualized based on disease burden and symptoms, including regular surveillance, symptomatic treatment, and intervention for complications.^1,3

Targeted systemic therapies, such as MEK inhibitors, are approved for selected patients with symptomatic or progressive PNs.⁷ Surgery may be considered for specific indications, recognizing the potential for morbidity.⁴

Optimal care requires a coordinated, multidisciplinary approach across the lifespan.⁵

References

1. Liao, 2025. Neurofibromatosis type 1 : A general review. https://www.doi.org/10.3340/jkns.2025.0073
2. Lee, 2023. Incidence and prevalence of neurofibromatosis type 1 and 2: A systematic review and meta-analysis. https://www.doi.org/10.1186/s13023-023-02911-2
3. Friedman, 1993 [updated 2025 Apr 3]. Neurofibromatosis 1. https://www.ncbi.nlm.nih.gov/books/NBK1109/
4. Lu, 2025. Neurofibromatosis type 1: Genetic mechanisms and advances in therapeutic innovation. https://www.doi.org/10.3390/cancers17233788
5. Lalvani, 2024. Neurofibromatosis type 1: Optimizing management with a multidisciplinary approach. https://www.doi.org/10.2147/jmdh.S362791
6. Legius, 2021. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. https://www.doi.org/10.1038/s41436-021-01170-5
7. Solares, 2021. Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas: A comprehensive review. https://www.doi.org/10.1016/j.esmoop.2021.100223

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