There are two types of neurofibromatosis, both inherited in an autosomal dominant manner, although some cases arise from spontaneous mutation. It results in benign tumours of the nervous system and bony and dermatological deformities.

Type I Neurofibromatosis – NF1

aka von Recklinghausen’s disease
Much more common than type 2 – accounts for 90% of cases

Genetics

  • Autosomal dominant inheritance, although widely varying penetrance
  • Gene on chromosome 17

Epidemiology and Aetiology

  • 1 in 2500
  • M:F – 1:1
  • Equal in all races

Signs and symptoms

Diagnosis requires ≥2 of the following:

Café-au-lait spots – just as the name suggests, pigmented brown skin patches. Often occur in the first year of life, grow and increase in number with age, and can be found all over the body. They do not increase the risk of skin cancer.

  • Diagnosis requires ≥6 spots of >155 diameter (post puberty) or >5mm (pre-puberty)

Neurofibromas – diagnosis requires ≥2 of any type, or ≥ 1 plexiform. They usually occur in late childhood. Some patients may only have a small number, whilst other have thousands. They come in four types:

  • Cutaneous – soft fleshy lumps found all over the body
  • Sub-cutaneous – harder and nodular
  • Nodular plexiform – usually involve the spinal roots, and grow through the intervertebral foramen where they may be palpable as dumbbell tumours. They can cause spinal cord compression. They may cause parasthesia when pressed
  • Diffuse plexiform
    • Both types of plexiform nodule are rarely able to become malignant

Freckling – typically occurs in the axillary and inguinal areas, although any skin fold may be affected. Usually present by the age of 10.
Optic glioma
≥ 2 Lisch nodules – these are small nodules on the iris. Usually regular, ≤ 2mm diameter and brown, 90% of patients have them by age 6. Best seen with a slit lamp.
Bone lesions

  • There are several bone lesions characteristic of neurofibromatosis, including subperiosteal bone cysts, scoliosis, thinning of the long bones, pseudarthrosis and absence of the greater wing of the sphenoid bone – which can result in a pulsating exophthalmos.

1st degree relative with NF1

 

Complications

Learning disability – usually mild, but is relatively common
Compression due to neurfibromas:

  • Nerves – compression
  • Gut – obstruction, ↑risk of bleeds
  • Hypertensioncan be due to renal artery stenosis, or more rarely phaechromocytoma
  • Malignancy – occurs in 5%. Can be an optic glioma, or malignancy of a neurofibroma (plexiform)
  • Epilepsy risk is very slightly increased

Diagnosis

Usually clinical. MRI can show changes in focal density at the site of neurofibromas.

Management

  • There is no curative treatment. Symptomatic neurofibromas are often removed, or in some cases, treated neurologically. Often removal of non-cutaneous lesions can be difficult as it results in loss of the nerve at the site of the lesion.
  • Many patients have hundreds of cutaneous lesions. It is not possible or practical to remove them all. Particularly troublesome lesions can catch on clothes and other items and should be removed. Often more will continue to grow throughout a patient’s life.
  • Genetic counselling should be given to all patients. If one parent is affected, the risk is 50% (autosomal dominant – although in reality risk may be lower due to variable penetrance)

Type 2 Neurofibromatosis – NF2

Genetics

  • Autosomal dominant
  • Gene on chromosome 22

Epidemiology and Aetiology

  • Much more rare than NF1: affects 1 in 35,000 individuals

Diagnosis

Is made if either of the following are present:

Bilateral vestibular schwannomas – can be seen on CT/MRI, but often present with bilateral sensorineural hearing loss in patients aged <30.  The schwannomas are actually a form of acoustic neuroma. They may also affect balance and cause facial weakness. The tumours themselves are benign but can cause compression, and increase intra-cranial pressure (ICP).
1st degree relative with NF2 AND, either:

  • Unilateral vestibular schwannoma, or
  • One of:
    • Neurofibroma
    • Menningioma – occur in 45% of patients, sometimes several are present.
    • Glioma
    • Scwannoma
    • Juvenile cataractaka – Juvenile posterior subcapsular lenticular opacity – usually is the first sign to occur. Can be useful to screen those with 1st degree relatives.

Management

Survival from diagnosis – typically 15 years
No curative treatment
Management based around screening – for the presence of the disease in at risk patients, and for tumours (particularly schwannomas) is those with known disease

  • Annual hearing tests are useful as a screening tool. Any patients with abnormalities should have an MRI.
  • Surgery should be used to remove schwannomas, but carries a risk of facial weakness and hearing loss.
  • No disease present at age 20 (on MRI) implies low risk (for offspring as well as patient). If no disease present at 30 (on MRI) then you can almost guarantee the gene hasn’t been inherited (but, be wary of a family history of late onset disease!)

Related Articles