Neurofibromatosis

Question 1

What is the definition of Neurofibromatosis?

Answer 1

An autosomal dominant genetic disorder affecting cells of neural crest origin, resulting in the development of multiple neurocutaneous tumours

Question 2

What is type 1 neurofibromatosis (NF1) characterised by?

Answer 2

Type 1 Neurofibromatosis (von Recklinghausen’s disease) is characterised by:

Peripheral and spinal neurofibromas

Multiple café au lait spots

Freckling (axillary/inguinal)

Optic nerve glioma

Lisch nodules (on iris)

Skeletal deformities

Phaeochromocytomas

Renal artery stenosis

Question 3

What is type 2 neurofibromatosis (NF2) characterised by?

Answer 3

Type 2 Neurofibromatosis is characterised by:

Schwannomas (often bilateral vestibular schwannomas)

Meningiomas

Gliomas

Cataracts

Question 4

What is the aetiology of neurofibromatosis?

Answer 4

Associated with multiple mutations in tumour suppressor genes NF1 (type 1) and NF2 (type 2)

Question 5

Is there anything specific about the epidemiology of neruofibromatosis?

Answer 5

No gender or racial predilection

Question 6

What are the presenting symptoms for NF1?

Answer 6

Type 1:

• Skin lesions
• Learning difficulties (40%)
• Headaches
• Disturbed vision (due to optic gliomas)
• Precocious puberty (due to lesions of the pituitary gland from an optic glioma involving the chiasm)

Question 7

What are the presenting symptoms for NF2?

Answer 7

Type 2:

• Hearing loss
• Tinnitus
• Balance problems
• Headache
• Facial pain
• Facial numbness

Question 8

Is there a family history associated with neurofibromatosis?

Answer 8

Yes, positive family history however 50% can be caused by new mutations

Question 9

What are the signs of NF1 on physical examination?

Answer 9

• 5+ café au lait macules of > 5 mm (prepubertal)
• 5+ café au lait macules of > 15 mm (post-pubertal)
• Neurofibromas (may appear as cutaneous nodules or complex plexiform neuromas)
• Freckling in armpit or groin
• Lisch nodules (hamartomas on the iris)
• Spinal scoliosis

Question 10

What are the signs of NF2 on physical examination?

Answer 10

Few or no skin lesions

Sensorineural deafness with facial nerve palsy or cerebellar signs (if the schwannoma is large)

Question 11

What are the appropriate investigations for neurofibromatosis?

Answer 11

• Ophthalmological assessment
• Audiometry
• MRI brain and spinal cord - for vestibular schwannomas, meningiomas and nerve root neurofibromas
• Skull X-ray (sphenoid dysplasia in NF1)

Genetic testing