Neurofibromatosis

Question 1

Definition of Neurofibromatosis Type 1 Gene

Answer 1

• Found on chromosome 17 = codes for protein called neurofibromin
• A tumour suppressor protein
• Mutations in this gene are inherited in an autosomal dominant pattern.

Question 2

Clinical features of neurofibromatosis type 1 (CRABBING)

Answer 2

Cafe-au-lait spots ( > 15mm diameter is sig in adults)
Relative with NF1
Axillary or inguinal freckling
BB - bony dysplasia such as bowing of a long bone or sphenoid wing dysplasia
I - Iris hamartomas (Lisch nodules) = yellow-brown spots on the iris
N - Neurofibromas
G - Glioma of the optic pathway

Question 3

Diagnosis

Answer 3

Diagnostic criteria.
- Genetic testing

Question 4

Treatment

Answer 4

There is no treatment for the underlying disease process. Management involves monitoring, managing symptoms and treating complications.

Question 5

Complications

Answer 5

• MALIGNANT PERIPHERAL NERVE SHEATH (MPNST)
• GASTROINTESTINAL STROMAL TUMOURS (GIST)
• Migraines
• Epilepsy
• Renal artery stenosis, causing hypertension
• Learning disability
• Behavioural problems (e.g., ADHD)
• Scoliosis of the spine
• Vision loss (secondary to optic nerve gliomas)
• Brain tumours
• Spinal cord tumours with associated neurology (e.g., paraplegia)
• Increased risk of cancer (e.g., breast cancer and leukaemia)

Question 6

Neurofibromatosis 2

Answer 6

• Found on chromosome 22
• Codes for a protein called merlin, a tumour suppressor protein in Schwann cells.
• Mutations in this gene lead to schwannomas (benign tumours of the Schwann cells). Inheritance is also autosomal dominant.
• Esp associated with acoustic neuromas which are tumours of the auditory nerve that innervates the inner ear.
  Surgery can be used to resect the tumours although there is a risk of permanent nerve damage

Question 7

EXAM TIP

Answer 7

An exam patient with bilateral acoustic neuromas almost certainly has neurofibromatosis type 2.