Neurofibromatosis

Question 1

Define neurofibromatosis

Answer 1

Autosomal dominant genetic disorder affecting cells of neural crest origin -> development of
multiple neurocutaneous tumours

Question 2

What are the causes/risk factors of neurofibromatosis?

Answer 2

Mutations in tumour suppressor genes NF1 and NF2

Type 1 NF (von Recklinghausen’s disease) – mutations in NF1 gene which encodes
neurofibromin
• Peripheral and spinal neurofibromas
• Café au lait spots
• Axillary/inguinal freckling
• Optic nerve glioma
• Lisch nodules (hamartomas on iris)
• Skeletal deformities
• Phaeochromocytoma
• Renal artery stenosis

Type 2 NF – mutations on NF2 gene which
encodes merlin
• Cataracts
• Meningioma
• Schwannoma e.g. acoustic neuroma
• Glioma

Question 3

What are the signs and symptoms of neurofibromatosis?

Answer 3

Type 1
• Café au lait spots
• Neurofibromas (may be associated with pain/tenderness)
• Freckling
• Learning difficulties – gross motor delay, incoordination
• Headaches
• Disturbed vision
• Precocious puberty (pituitary lesion from optic glioma)
• GI problems e.g. constipation, bleeding, pain (hyperganglionosis of the colon)

Type 2
• Headache
Sensorineural deafness
• Hearing loss
• Tinnitus
• Balance problems
Facial nerve palsy
• Facial pain/numbness

Question 4

What investigations are carried out for neurofibromatosis?

Answer 4

• Opthalmological assessment
• Audiometry
• MRI brain and spinal cord: For vestibular schwannomas, meningiomas and nerve root neurofibromas.
• Skull X-ray: Sphenoid dysplasia in type 1 NF.
• Genetic testing: Possible but difficult as the NF1 gene is very long.