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

Definition of Neurofibromatosis 2

Answer 3

• 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 4

Neurofibromatosis 2 Signs

Answer 4

Bilateral vestibular schwannomas,
Multiple intracranial schwannomas,
Mengiomas
Ependymomas

Question 5

Diagnosis

Answer 5

Diagnostic criteria.
- Genetic testing

Question 6

Treatment

Answer 6

There is no treatment for the underlying disease process. Management involves monitoring, managing symptoms and treating complications:
- Analgesia: NSAIDs /Opiates for pain related to plexiform neurofibromas.
- Antihypertensives: ACE-I or CCB are recommended for hypertension secondary to renal artery stenosis in NF1 patients.
- Malignant Peripheral Nerve Sheath Tumours (MPNSTs): MPNSTs require aggressive treatment with surgery, radiation therapy and chemotherapy. The MEK inhibitor Selumetinib has shown promise in shrinking tumours in children with NF1.

Question 7

Complications

Answer 7

• 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 8

EXAM TIP

Answer 8

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