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Neurofibromatosis Type 1 (NF1), also known as von Recklinghausen disease, is a common autosomal dominant neurocutaneous disorder characterized by cutaneous, neurologic, skeletal, and ocular abnormalities, as well as a predisposition to benign and malignant tumors, especially neurogenic tumors.

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https://www.youtube.com/watch?v=nixcoQW5usI

Etiopathology

Genetic basis:

Clinical manifestations

Development of clinical features of neurofibromatosis type 1: https://doi.org/10.1038/nrdp.2017.4

![The timing of the clinical manifestations and the severity of features can vary between individuals. The skeletal abnormalities include scoliosis and long bone dysplasia; although not part of the diagnostic criteria, scoliosis is the most common skeletal manifestation of neurofibromatosis type 1 and is found in up to 30% of children. Dysplasia of a long bone is found in ∼2% of children with NF1. Behavioural manifestations can include cognitive impairment (observed in ∼80% of children), attention-deficit/hyperactivity disorder (ADHD; a prevalence of ∼30–50% in children) and autism spectrum disorder (ASD; ∼40% of children with NF1 show features associated with ASD and 13% have autism). Tumours can include malignant peripheral nerve sheath tumours (MPNSTs) and gliomas. The lifetime risk of developing MPNSTs associated with neurofibromatosis type 1 is between 8% and 16%; these tumours are the most common in the third decade of life, but can occur at any age. Between 15-20% of children with NF1 will develop an optic pathway glioma, which is symptomatic in 7–10% of individuals, whereas 5% of patients have brainstem gliomas. Other, albeit rare, manifestations include juvenile xanthogranuloma, pheochromocytomas and gastrointestinal stromal tumours. CALM, café-au-lait macule.

Gutmann, D., Ferner, R., Listernick, R. et al. Neurofibromatosis type 1. Nat Rev Dis Primers 3, 17004 (2017). https://doi.org/10.1038/nrdp.2017.4](attachment:338dff4d-3c9e-4317-82e4-6e5a5db15723:41572_2017_Article_BFnrdp20174_Fig2_HTML.webp)

The timing of the clinical manifestations and the severity of features can vary between individuals. The skeletal abnormalities include scoliosis and long bone dysplasia; although not part of the diagnostic criteria, scoliosis is the most common skeletal manifestation of neurofibromatosis type 1 and is found in up to 30% of children. Dysplasia of a long bone is found in ∼2% of children with NF1. Behavioural manifestations can include cognitive impairment (observed in ∼80% of children), attention-deficit/hyperactivity disorder (ADHD; a prevalence of ∼30–50% in children) and autism spectrum disorder (ASD; ∼40% of children with NF1 show features associated with ASD and 13% have autism). Tumours can include malignant peripheral nerve sheath tumours (MPNSTs) and gliomas. The lifetime risk of developing MPNSTs associated with neurofibromatosis type 1 is between 8% and 16%; these tumours are the most common in the third decade of life, but can occur at any age. Between 15-20% of children with NF1 will develop an optic pathway glioma, which is symptomatic in 7–10% of individuals, whereas 5% of patients have brainstem gliomas. Other, albeit rare, manifestations include juvenile xanthogranuloma, pheochromocytomas and gastrointestinal stromal tumours. CALM, café-au-lait macule.

Gutmann, D., Ferner, R., Listernick, R. et al. Neurofibromatosis type 1. Nat Rev Dis Primers 3, 17004 (2017). https://doi.org/10.1038/nrdp.2017.4

![Manifestations of neurofibromatosis type 1. ADHD attention deficit hyperactivity disorder, GIST gastrointestinal stromal tumor, JMML juvenile myelomonocytic leukemia, MPNST malignant peripheral nerve sheath tumor

Sunder-Plassmann, V., Azizi, A.A., Farschtschi, S. et al. Neurofibromatosis type 1 adult surveillance form for Austria. Wien Klin Wochenschr (2024). https://doi.org/10.1007/s00508-024-02443-0](attachment:c65c4ae6-e87a-4fc9-a303-77b45d8b3397:508_2024_2443_Fig1_HTML.webp)

Manifestations of neurofibromatosis type 1. ADHD attention deficit hyperactivity disorder, GIST gastrointestinal stromal tumor, JMML juvenile myelomonocytic leukemia, MPNST malignant peripheral nerve sheath tumor

Sunder-Plassmann, V., Azizi, A.A., Farschtschi, S. et al. Neurofibromatosis type 1 adult surveillance form for Austria. Wien Klin Wochenschr (2024). https://doi.org/10.1007/s00508-024-02443-0

![Common manifestations of NF1. Café-au-lait macules (a), multiple neurofibromas of the face (b), multiple Lisch nodules (c), optic nerve glioma (d), and contrast-enhanced magnetic resonance image

Binkley, E., Traboulsi, E.I., Singh, A.D. (2019). Neuro-oculocutaneous Syndromes (Phakomatoses). In: Singh, A., Damato, B. (eds) Clinical Ophthalmic Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-04113-7_9](attachment:d838b724-2012-4c62-ac24-56854bcffba6:image.png)

Common manifestations of NF1. Café-au-lait macules (a), multiple neurofibromas of the face (b), multiple Lisch nodules (c), optic nerve glioma (d), and contrast-enhanced magnetic resonance image

Binkley, E., Traboulsi, E.I., Singh, A.D. (2019). Neuro-oculocutaneous Syndromes (Phakomatoses). In: Singh, A., Damato, B. (eds) Clinical Ophthalmic Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-04113-7_9

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Representative images:

• Cutaneous manifestations
• Osseous manifestations
• CNS manifestations </aside>

Tumors in NF1:

Complications

• Neurologic: Seizures, cognitive deficits, brain tumors
• Skeletal: Scoliosis, pseudoarthrosis