Neurofibromatosis

Question 1

What is neurofibromatosis?

Answer 1

Autosomal dominant genetic disorder affecting cells of neural crest origin that leads to development of multiple neurocutanous tumours

Question 2

What is the neural crest and what does it give rise to?

Answer 2

structure in the embryo that leads to:

• PNS
• smooth muscle cells of the cardiovascular system
• pigment cells in the skin
• craniofacial bones, cartilage, and connective tissue

Question 3

What mutations cause neurofibromatosis?

Answer 3

mutations in tumour suppressor genes: NF1 and NF2

Question 4

How does NF1 mutation lead to neurofibromatosis?

Answer 4

NF1 on chromosome 17 leads to mutation in neurofibromin leads to type 1 (most common)

Question 5

How does NF2 mutation lead to neurofibromatosis?

Answer 5

NF2 on chromosome 22 leads to mutation in merlin (schwannomin) leads to Type 2

Question 6

What are RF for neurofibromatosis?

Answer 6

1. FHx (autosomal inheritance)

2. Severe crush trauma

Question 7

What are the general Type 1 symptoms?

Answer 7

1.	Skin lesions 
Pain related to those skin lesions
2.	Learning difficulties 
3.	Headaches 
4.	Disturbed vision 
5.	GI: severe constipation

Question 8

What skin lesions are present in Typ1?

Answer 8

cafe au lait macules

Question 9

How do you classify cafe au lait macules?

Answer 9

-Prepubertal:
5+ café au lait macules of >5mm
-Post-pubertal:
5+ café au lait macules 3 of >15mm

Question 10

What are key features of Type 1?

Answer 10

• cuatneous, subcutaneous or diffuse plexiform skin lesions
• armpit freckling
• lisch nodules

Question 11

What are specific CNS signs of Type 1 neurofibromatosis?

Answer 11

Signs of hydrocephalus, brain tumours, cerebellar abnormalities e.g. seizures

Question 12

What are specific PNS signs of Type 1 neurofibromatosis?

Answer 12

1. palpable neck mass
2. brachial plexuses
3. groin
4. Hunter’s canal
5. popliteal fossae

Question 13

What are specific skeletal deformities signs of Type 1 neurofibromatosis?

Answer 13

1. tibial dysplasia or pseudoarthritis
2. sphenoid wing dysphasia
3. Pectus excavatum/carinatum
4. genu valgum/varum
5. ankle valgus
6. pes planus

Question 14

What are specific GI signs of Type 1 neurofibromatosis?

Answer 14

signs of bleeding e.g. melaena, haematochezia etc

Question 15

What are specific vascular signs of Type 1 neurofibromatosis?

Answer 15

neurological problems, abdominal pain, haemorrhage

Question 16

What are Type 2 symptoms?

Answer 16

1. Hearing loss
2. Tinnitus
3. Balance problems/vertigo
4. Headache
5. Facial pain
6. Facial numbness

May be bilateral!

Question 17

What investigations are done for neurofibromatosis?

Answer 17

1. FULL BODY EXAMINATION
2. Ophthalmological assessment
3. Hearing test –if NF2 is suspected

Question 18

What scans should be done for neurofibromatosis?

Answer 18

1. CT or MRI may be required
2. Identify vestibular schwannoma, meningiomas and nerve root neurofibromas
3. Genetic testing – NF1 mutation