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# Neurofibromatosis (types 1 and 2)

Neurofibromatosis is a group of inherited conditions that cause benign tumours along nerves, plus skin spots (type 1) or hearing nerve tumours (type 2).

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Vestibulocochlear nerve (VIII)](https://durgical.com/en/anatomy/vestibulocochlear-nerve/)
- [Neck nerve roots](https://durgical.com/en/anatomy/anterior-root-of-spinal-nerve/)
- [Optic nerve](https://durgical.com/en/anatomy/optic-nerve/)
- [Skin](https://durgical.com/en/anatomy/skin/)
- [Iris](https://durgical.com/en/anatomy/iris/)
- [Internal acoustic meatus](https://durgical.com/en/anatomy/internal-acoustic-meatus/)
- [Cochlea](https://durgical.com/en/anatomy/cochlea/)
- [Dorsal root ganglia](https://durgical.com/en/anatomy/spinal-ganglion/)
- [Spinal cord](https://durgical.com/en/anatomy/spinal-cord/)
- [Mid-back nerve roots](https://durgical.com/en/anatomy/anterior-root-of-spinal-nerve-spine-and-pelvis/)

## Why it happens

- [Mendelian inheritance: autosomal dominant, recessive and X-linked](https://durgical.com/en/general-pathology/mendelian-inheritance-autosomal-dominant-recessive-and-x-linked/)
- [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/)
- [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/)
- [Receptor tyrosine kinases](https://durgical.com/en/biochemistry/topics/receptor-tyrosine-kinases/)
- [Peripheral nerve: endoneurium, perineurium, epineurium; myelin](https://durgical.com/en/histology/peripheral-nerve-endoneurium-perineurium-epineurium-myelin/)

## What it is

A group of autosomal dominant tumour-predisposition syndromes affecting the [nervous system](https://durgical.com/en/anatomy/system/nervous-system/) and skin. Type 1 (NF1) causes café-au-lait spots, neurofibromas and optic gliomas; type 2 (now called NF2-related schwannomatosis) causes bilateral vestibular schwannomas and other nervous system tumours.

## Who gets it

NF1 is one of the most common single-gene disorders, about 1 in 3,000 to 4,000 people worldwide, with no ethnic predilection; NF2 is much rarer, about 1 in 33,000. About half of cases arise from a new mutation with no family history. In Colombia both are followed in genetics, neurology and paediatric services and are rare diseases in the national registry.

## Causes

- NF1: pathogenic variant in the NF1 gene (chromosome 17), which encodes neurofibromin, a negative regulator of the RAS pathway
- NF2: pathogenic variant in the NF2 gene (chromosome 22), which encodes merlin (schwannomin)
- Autosomal dominant inheritance with complete penetrance but very variable expression
- About half of cases are de novo; mosaic forms give segmental disease

## Risk factors

- An affected parent (50% risk to each child)
- Higher paternal age for de novo variants

## Pathophysiology

Both genes are tumour suppressors. A second hit in the remaining normal copy within a cell allows uncontrolled growth: in NF1, loss of neurofibromin leaves RAS signalling on, driving neurofibromas from Schwann cells and other nerve sheath cells, optic pathway gliomas and pigment changes; in NF2, loss of merlin leads to schwannomas (classically on both vestibular nerves), meningiomas and ependymomas.

## Classification

- NF1 (von Recklinghausen disease): café-au-lait macules, axillary or inguinal freckling, neurofibromas, Lisch nodules, optic glioma, bone dysplasias
- NF2-related schwannomatosis: bilateral vestibular schwannomas, meningiomas, ependymomas, juvenile cataract
- Non-NF2 schwannomatosis: multiple painful schwannomas without vestibular tumours (SMARCB1, LZTR1)

## Symptoms and signs

- NF1: six or more café-au-lait spots (larger than 5 mm before puberty, 15 mm after), often present at birth or in early childhood
- NF1: freckling in the armpits or groin, and cutaneous neurofibromas that appear from adolescence
- NF1: plexiform neurofibromas, Lisch nodules ([iris](https://durgical.com/en/anatomy/iris/) hamartomas), learning difficulties and ADHD, short stature, macrocephaly
- NF1: optic pathway glioma with reduced vision or early puberty; scoliosis and tibial bowing (pseudarthrosis)
- NF2: progressive hearing loss, tinnitus and imbalance in adolescence or early adulthood
- NF2: facial weakness, headache, [spinal cord](https://durgical.com/en/anatomy/spinal-cord/) or root symptoms, and juvenile cataract

## Red flags

- A plexiform neurofibroma that grows quickly, becomes hard or newly painful, or causes new weakness (malignant peripheral nerve sheath tumour)
- Loss of vision, a pale [optic disc](https://durgical.com/en/anatomy/optic-disc/) or early puberty in a child with NF1 (optic glioma)
- High blood pressure in a young person with NF1 ([renal artery](https://durgical.com/en/anatomy/renal-artery/) stenosis or pheochromocytoma)
- Sudden hearing loss, facial weakness or new limb weakness in NF2
- Headache with vomiting or reduced consciousness (raised intracranial pressure from a tumour)

## Diagnosis

**Clinical**
Mainly clinical, with revised international consensus criteria (2021). NF1 needs two or more of: six or more café-au-lait macules, freckling, two or more neurofibromas or one plexiform, optic glioma, two or more Lisch nodules or choroidal anomalies, a typical bone lesion, a heterozygous NF1 variant, or one feature plus an affected parent. NF2 is classically diagnosed by bilateral vestibular schwannomas. Annual [skin](https://durgical.com/en/anatomy/skin/), eye, blood pressure, growth and [spine](https://durgical.com/en/anatomy/region/spine/) examination.

**Tests**
Genetic testing for NF1 or NF2 variants in unclear or mosaic cases and for family planning. Audiometry in NF2. Plasma or urine metanephrines if pheochromocytoma is suspected.

**Imaging**
Contrast MRI of the brain and internal auditory canals in NF2; MRI of the spine for spinal tumours. In NF1, MRI of the orbits and brain when there are visual or neurological signs (often showing focal T2 bright areas); whole-body MRI may map plexiform tumours. X-rays for scoliosis and tibial bowing.

## Differential diagnosis

- Legius syndrome (café-au-lait spots without tumours, SPRED1)
- Isolated café-au-lait spots or McCune-Albright syndrome (irregular coast-of-Maine spots)
- Sporadic unilateral vestibular schwannoma in an older adult
- Non-NF2 schwannomatosis
- Tuberous sclerosis complex (different skin lesions: ash-leaf macules, angiofibromas)

## Goal of treatment

No cure: the aims are regular surveillance to catch complications early, treating tumours that cause symptoms, preserving vision and hearing, and supporting learning, development and quality of life.

## Treatment

**Follow-up**
Multidisciplinary follow-up with yearly review of skin, vision, blood pressure, growth, spine and development, with genetic counselling for the family.

**Medical**
MEK inhibitors can shrink symptomatic inoperable plexiform neurofibromas in NF1; chemotherapy is used for optic gliomas that threaten vision; anti-VEGF therapy may slow growing vestibular schwannomas in NF2.

**Surgical**
Surgical removal of painful, disfiguring or compressing neurofibromas and schwannomas, and resection of spinal tumours or pheochromocytoma; spine surgery for severe scoliosis.

**Procedure**
Stereotactic radiosurgery is an option for selected vestibular schwannomas; hearing implants (cochlear or auditory brainstem implants) restore some hearing in NF2.

**Rehabilitation**
Educational support for learning difficulties and ADHD, physical therapy, and hearing and vision rehabilitation.

## Complications

- Malignant peripheral nerve sheath tumour (lifetime risk around 8–13% in NF1)
- Optic glioma with vision loss; other brain tumours
- Hypertension from renal artery stenosis or pheochromocytoma
- Scoliosis and tibial pseudarthrosis
- Learning disability and ADHD
- Higher risk of breast cancer in women with NF1 and of some other cancers
- NF2: deafness, facial palsy, brainstem and spinal cord compression

## Prognosis

NF1 is very variable: many people have a normal life with mainly skin findings, but life expectancy is reduced on average by cancer and vascular complications. NF2 usually leads to deafness and multiple tumours and has higher morbidity; early diagnosis and specialised care improve outcomes.

## Test yourself

Think of the answer, then tap the question to see it.

## What is the inheritance pattern of neurofibromatosis types 1 and 2?

Autosomal dominant, with about half of cases arising from a new (de novo) variant.

## What are three classic findings of NF1?

Six or more café-au-lait spots, axillary or inguinal freckling and neurofibromas; also Lisch nodules and optic glioma.

## What tumour defines NF2?

Bilateral vestibular schwannomas, causing hearing loss, tinnitus and imbalance.

## Which genes and proteins are affected in NF1 and NF2?

NF1 (chromosome 17) encodes neurofibromin, a RAS-pathway regulator; NF2 (chromosome 22) encodes merlin.

## Which complication is suggested by rapid growth and new pain in a plexiform neurofibroma?

Malignant transformation into a malignant peripheral nerve sheath tumour.

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## Related conditions

- [Vestibular schwannoma (acoustic neuroma)](https://durgical.com/en/conditions/vestibular-schwannoma/)
- [Meningioma](https://durgical.com/en/conditions/meningioma/)
- [Scoliosis](https://durgical.com/en/conditions/scoliosis/)
- [Phaeochromocytoma](https://durgical.com/en/conditions/phaeochromocytoma/)
- [Arterial hypertension](https://durgical.com/en/conditions/arterial-hypertension/)
- [Hearing loss (conductive and sensorineural, including sudden hearing loss)](https://durgical.com/en/conditions/hearing-loss/)
- [Cataract](https://durgical.com/en/conditions/cataract/)
- [Attention-deficit/hyperactivity disorder (ADHD)](https://durgical.com/en/conditions/attention-deficit-hyperactivity-disorder/)
- [Breast cancer](https://durgical.com/en/conditions/breast-cancer/)
- [Childhood brain tumours (medulloblastoma, pilocytic astrocytoma, craniopharyngioma)](https://durgical.com/en/conditions/childhood-brain-tumours/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Neurofibromatosis type 1: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/neurofibromatosis-type-1/) (MedlinePlus Genetics, US National Library of Medicine, 2026); [Neurofibromatosis type 2: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/neurofibromatosis-type-2/) (MedlinePlus Genetics, US National Library of Medicine, 2026).

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Source: https://durgical.com/en/conditions/neurofibromatosis/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/neurofibromatosis/