Neurofibromatosis

Question 1

Define Neurofibromatosis

Answer 1

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

Question 2

What is the difference between Type I and Type II Neurofibromatosis

Answer 2

Type I (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 and renal artery stenosis

Type II: Characterised by schwannomas e.g. bilateral vestibular schwannomas (acoustic neuromas), peripheral/spinal schwannomas, meningiomas, gliomas, cataracts.

Question 3

Aetiology of Neurofibromatosis

Answer 3

Autosomal dominant inheritance
Multiple mutations in tumour suppressor genes NF1 and NF2

Type I: Mutation in NF1 gene (chromosome 17)
Type II: Mutation in NF2 (chromosome 22)

RF: parent with NF1, severe crush trauma

Question 4

Symptoms of Type I Neurofibromatosis

Answer 4

Skin lesions
Learning difficulties (40%), gross motor delay, general incoordination
Headaches or pain in any location
Disturbed vision (optic glioma 15%)
Precocious puberty
Severe constipation, obstipation, abdominal pain, GI bleeding

Question 5

Symptoms of Type II Neurofibromatosis

Answer 5

Hearing loss
Tinnitus 
Balance problems
Headache
Facial pain
Numbness

Question 6

Signs of Type I Neurofibromatosis on examination

Answer 6

> 5 café au lait macules >5mm (pre-pubertal)
15mm (post-pubertal individuals)
Neurofibromas (cutaneous nodules or plexiform neuromas)
Freckling in armpit or groin
Lisch nodules (hamartomas on iris - look like outpouchings)
Spinal scoliosis

Question 7

Signs of Type II Neurofibromatosis on examination

Answer 7

Few or no skin lesions
Sensorineural deafness with facial nerve palsy
Schwannoma large -> cerebellar signs

Question 8

Investigations for Neurofibromatosis

Answer 8

MRI/CT: Defines the presence, nature and/or extent of lesion(s)
May show evidence of tumour growth
PET scan: Same as MRI/CT but useful for distinguishing malignant peirpheral nerve sheath tumours (MONSTs) from benign neurofibromas

Skull X-ray: sphenoid dysplasia (type I)

Biopsy: Histological features of a neurofibroma

Genetic testing: NF1 or NF2 mutation