Neurofibromatosis

Question 1

Definition

Answer 1

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

Question 2

Type 1 neurofibromatosis

Answer 2

Type 1 Neurofibromatosis (von Recklinghausen’s disease)

o 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

Type 2 neurofibromatosis

Answer 3

Type 2 Neurofibromatosis

o Characterised by:
• Schwannomas (often bilateral vestibular schwannomas)
• Meningiomas
• Gliomas
• Cataracts

Question 4

Aetiology

Answer 4

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

Question 5

Epidemiology

Answer 5

No gender or racial predilection

Question 6

Presenting symptoms (type 1)

Answer 6

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

• Type 1
o Skin lesions
o Learning difficulties (40%)
o Headaches
o Disturbed vision (due to optic gliomas)
o Precocious puberty (due to lesions of the pituitary gland from an optic glioma
involving the chiasm)

Question 7

Presenting symptoms (type 2)

Answer 7

• Type 2

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

Question 8

Signs on physical examination (type 1)

Answer 8

o 5+ café au lait macules of > 5 mm (prepubertal)
o 5+ café au lait macules of > 15 mm (post-pubertal)

o Neurofibromas (may appear as cutaneous nodules or complex plexiform neuromas)

o Freckling in armpit or groin

o Lisch nodules (hamartomas on the iris)

o Spinal scoliosis

Question 9

Signs on physical examination (type 2)

Answer 9

o Few or no skin lesions

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

Question 10

Investigations

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