Neurofibromatosis

Question 1

Define 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 are the 2 subtypes of neurofibromatosis?

Answer 2

1. Type 1 Neurofibromatosis (von Recklinghausen’s disease)

2. Type 2 Neurofibromatosis

Question 3

What are the characteristics of Type 1 Neurofibromatosis?

Answer 3

Characterised by:

Skin signs;
• Multiple café au lait spots
• Freckling (axillary/inguinal)
• Peripheral and spinal neurofibromas (larger lumps more likely to cause problems)

• Optic nerve glioma
• Lisch nodules (on iris)
• Skeletal deformities
• Phaeochromocytomas
• Renal artery stenosis

Question 4

Are these tumours benign or malignant?

Why are they of particular worry?

Answer 4

Benign

Issue is they may cause damage through compression of nerves and tissue.

Question 5

What are the characteristics of Type 2 Neurofibromatosis?

Answer 5

Type 2 Neurofibromatosis
○ Characterised by:
• Schwannomas (often bilateral vestibular schwannomas)
• Meningiomas
• Gliomas
• Cataracts

Question 6

Explain the aetiology/risk factors of neurofibromatosis

Answer 6

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

Summarise the epidemiology of neurofibromatosis
• No gender or racial predilection

Question 7

Recognise the presenting symptoms of type 1 neurofibromatosis

Answer 7

• Positive family history (however, 50% are caused by new mutations)

○ 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 8

Recognise the presenting symptoms of type 2 neurofibromatosis

Answer 8

- Hearing loss
○ Tinnitus
○ Balance problems
○ Headache
○ Facial pain
○ Facial numbness

Question 9

Recognise the presenting signs of neurofibromas type 1 and 2

Answer 9

Type 1;

• 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

• Type 2
○ Few or no skin lesions
○ Sensorineural deafness with facial nerve palsy or cerebellar signs (if the schwannoma is large - vestibulocochlear schwanoma)

Question 10

Identify appropriate investigations for neurofibromatosis

Answer 10

• 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