Neurofibromatosis

Question 1

Define

Answer 1

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

Type 1 Neurofibromatosis (von Recklinghausen’s disease)

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

Type 2 Neurofibromatosis

Characterised by:

• Schwannomas (often bilateral vestibular schwannomas)
• Meningiomas
• Gliomas
• Cataracts

Question 2

Causes

Answer 2

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

Question 3

Epidemiology

Answer 3

No gender or racial predilection

Question 4

Symptoms

Answer 4

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

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)

Type 2

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

Question 5

Signs

Answer 5

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)

Question 6

Investigations

Answer 6

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