Neurofibromatosis type 1
Last update: January 2026
Neurofibromatosis type 1 (NF1, ORPHA:636, OMIM: 162200, MONDO:0018975) is a complex multisystem-tumour predisposition syndrome and occurs in 1 in 2,000 - 2,500 individuals. Individuals with NF1 have darker coloured spots (birthmarks) on the skin, also known “café-au-lait macules”. They develop noncancerous tumours along the nerves of the skin, and other regions of the body. Some children are born with a growing tumour on a long region of a nerve with a potential to cause symptoms by pressure on organs or nerves (plexiform). It is possible that such a tumour will suffer a malignant transformation to a specific cancer known as malignant peripheral nerve sheath tumour (MPNST) in adolescence or as an adult. Children in particular may suffer from tumours developing on the nerve from the eye to the brain, that may lead to blindness (optic pathway glioma). Individuals with NF1 have an increased risk for a number of other rare tumours. Females with NF1 between 30 and 50 years have a higher chance of developing breast cancer. NF1 affected people also have an increased risk of high blood pressure and skeletal problems such as a high curvature of the spine. Many patients suffer from some form of learning disability, concentration or communication problem.
Mosaic NF1 (ORPHA: 634461) refers to a clinical syndrome with localized symptoms of NF1 (e.g. café-au-lait macules in only one part of the body), and often milder form of NF1. It results from a spontaneous occurrence of the gene fault during development as an embryo, i.e. not all body-cells contain the genetic mutation.
Neurofibromatosis-Noonan syndrome (NFNS, ORPHA: 638, OMIM:601321) involves a clinical syndrome with overlapping clinical symptoms, like café-au-lait macules from NF1 and heart defects from Noonan Syndrome. Legius syndrome is another NF1-like presenting syndrome, with patients presenting with café-au-lait macules but without neurofibromas or tumorous complications typical of NF1. It requires genetic testing for correct diagnosis (Noonan syndrome, Legius syndrome or NF1), whereafter the applicable surveillance and care pathway can be defined.
NF1 is caused by a genetic alteration in one of the two copies of the NF1 gene on chromosome 17.
The condition is inherited from parent to offspring with a chance of 1 in 2. Half of the individuals with NF1 do not have an affected parent and the genetic error started with the person. This alteration can be detected by a genetic analysis of the blood to confirm diagnosis. In mosaic NF1, the likelihood of passing the disease down to children may be reduced from the usual 50% and depends on whether the gonadal area is affected.
Children have to be monitored on a yearly (<10 yrs) to 1x/2 years basis for vision (< 10 yrs), blood pressure, growth of plexiform neurofibromas, development, skeletal problems and school career. A whole-body MRI at the age of 16-18 years to assess the presence or absence of tumours may be helpful to identify those adults in need for specific yearly follow-up. Otherwise, a follow-up at least every 3 years might be sufficient. It is recommended that females have yearly breast MRI (preferred) or mammograms preferably starting at the age of 30 years. ERN GENTURIS has developed a guideline for tumour surveillance in NF1: ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1.
GeneReviews® - Neurofibromatosis type 1
Orphanet: Neurofibromatosis type 1
Orphanet: Mosaic neurofibromatosis type 1
OMIM: neurofibromatosis type 1
Clingen: neurofibromatosis type 1
Orphanet: neurofibromatosis-Noonan syndrome
OMIM: neurofibromatosis-Noonan syndrome
ERN CRANIO (regarding the craniofacial anomalies of neurofibromatosis)
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Clinical practice guidelines |
ERN GENTURIS care pathway |
ERN GENTURIS patient journey |
ERN GENTURIS publications |
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Written by ERN GENTURIS |
Endorsed by ERN GENTURIS* |
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Neurofibromatosis 1 guideline - ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1. |
Thematic Group 1: Schwannomatosis and neurofibromatosis Neurofibromatosis type 1 (NF1)
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* ERN GENTURIS uses AGREE II as a tool for the endorsement of guidelines. The quality of the guideline is evaluated through assessing the rigor and transparency of the guideline development process. The content of the guideline is not evaluated, although selection of the guideline for endorsement includes expert opinion on the usefulness of the content of the guideline.
ERN GENTURIS webinars - Thematic group 1: Neurofibromatosis
Neurofibromatosis type 1 (NF1)
A list of healthcare providers with expertise inThematic Group 1: schwannomatosis and neurofibromatosis can be found here.
A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.