Neurofibromatosis

Question 1

What is neurofibromatosis?

Answer 1

Autosomal dominant disorder affecting cells of neural crest origin, resulting in development of multiple neurocutaneous tumours.

Question 2

What are the types of neurofibromatosis?

Answer 2

• TYPE 1 aka von Recklinghausen’s disease characterised by café au lait spots, multiple neurofibromas, and iris Lisch nodules.
• TYPE 2: characterised by schwannomas, for example, bilateral vestibular schwannomas (acoustic neuromas), peripheral/spinal schwannomas, meningiomas, gliomas and cataracts

Question 3

What is the aetiology of neurofibromatosis?

Answer 3

• Type 1: mutations in NF1 gene (Chr17) which encodes neurofibromin. Mutations result in excessive activity of the protooncogene p21-ras, leading to dysplasias and neoplasias
• Type 2: mutations in NF2 gene (Chr22) which encodes merlin (or scwannomin)

Question 4

What is the epidemiology of neurofibromatosis: Gender? Ethnicity? Age?

Answer 4

No gender or racial predilection. NF1 presents before age of 10, NF2 in early adulthood

Question 5

What are the signs and symptoms of NF1? (x3 +4)

Answer 5

• SKIN LESIONS: (1) >5 café au lair macules of more than 5mm in pre-pubertal individuals, or at least 15mm in post-pubertal, (2) neurofibromas appearing peripherally or over spine as cutaneous nodules or complex plexiform neuromas, (3) freckling in armpit or groin
• EYES: optic nerve glioma (may disturb vision, or lead to precocious puberty from lesions of the pituitary involving the chiasm), Lisch nodules (hamartomas on iris)
• SKELETAL DEFORMITIES: scoliosis, sphenoid wing dysplasia
• Learning difficulties
• Headache

Question 6

What are the signs and symptoms of NF2? (x4)

Answer 6

• Sensorineural hearing loss, and tinnitus from acoustic neuromas
• Facial nerve palsy or cerebellar signs if schwannoma large
• Few or no skin lesions
• Headache

Question 7

What are complex plexiform neuromas?

Answer 7

Soft, flaccid, and pinkish-white, and frequently can be invaginated.

Question 8

What do Lisch nodules look like?

Answer 8

Brown regions in iris

Question 9

What are the investigations for neurofibromatosis? (x5)

Answer 9

• Ophthalmoscopy
• Audiometry
• MRI BRAIN AND SPINAL CORD: for vestibular schwannomas, meningiomas, nerve root neurofibromas
• SKULL X-RAY: sphenoid dysplasia in NF1
• GENETIC TESTING: difficult as NF1 is a very long gene