Neurofibromatosis

Question 1

Type

Answer 1

Neurofibromatosis type 1 is more common than type 2

Question 2

Genetics for NF type 1

Answer 2

The neurofibromatosis type 1 gene is found on chromosome 17.

It codes for a protein called neurofibromin, which is a tumour suppressor protein.

Inheritance of mutations in this gene is autosomal dominant.

Question 3

Clinical Features of NF

Answer 3

C – Café-au-lait spots (6 or more) measuring ≥ 5mm in children or ≥ 15mm in adults

R – Relative with NF1

A – Axillary or inguinal freckles

BB – Bony dysplasia such as Bowing of a long bone or sphenoid wing dysplasia

I – Iris hamartomas (Lisch nodules) (2 or more) are yellow brown spots on the iris

N – Neurofibromas (2 or more) or 1 plexiform neurofibroma

G – Glioma of the optic nerve

Question 4

Diagnosis

Answer 4

Diagnosis is based on clinical criteria and no investigations are required to make a definitive diagnosis.

Genetic testing can be used where there is doubt.

Xrays can be used to investigate bone pain and bone lesions.

Imaging with CT and MRI scans can be used to investigate lesions in the brain, spinal cord and elsewhere in the body.

Question 5

Complications

Answer 5

Migraines
Epilepsy
Renal artery stenosis causing hypertension
Learning and behavioural problems (e.g. ADHD)
Scoliosis of the spine
Vision loss (secondary to optic nerve gliomas)
Malignant peripheral nerve sheath tumours
Gastrointestinal stromal tumour (a type of sarcoma)
Brain tumours
Spinal cord tumours with associated neurology (e.g. paraplegia)
Increased risk of cancer (e.g. breast cancer)
Leukaemia

Question 6

Management

Answer 6

There is no treatment of the underlying disease process or to prevent the development of neurofibromas or complications.

Management is to control symptoms, monitor the disease and treat complications.

NF 2: surgical tumour resection

Question 7

Genetics for NF type 2

Inheritance

Answer 7

neurofibromatosis type 2 gene is found on chromosome 22

It codes for a protein called merlin, which is a tumour suppressor protein particularly important in Schwann cells. Mutations in this gene lead to the development of schwannomas (benign nerve sheath tumours of the Schwann cells)

Inheritance is autosomal dominant.

Question 8

NF 2 clinical features

Answer 8

Neurofibromatosis type 2 is most associated with acoustic neuromas. These are tumours of the auditory nerve innervating the inner ear.

Also more associated with meningiomas

Symptoms of an acoustic neuroma are:

• Hearing loss
• Tinnitus
• Vertigo