neurofibromatosis Flashcards
(21 cards)
definition of neurofibromatosis
autosomal dominant genetic disorder
affects cells of neural crest origin = multiple neurocutaneous tumours
Type 1 (von Recklinghausen’s disease)
type 2
Type 1 neurofibromatosis (von Recklinghausen’s disease)
- peripheral and spinal neurofibromas
- cafe au lait spots
- freckling - axillary/inguinal
- optic nerve glioma
- Lisch nodules - on iris
- skeletal deformities
- phaechromocytomas
- renal artery stenosis
type 2 neurofibromatosis
schwannomas eg ilateral vestibular scheannomas (acoustic neuromas), peripheral/spinal schwannomas, meningiomas, gliomas, cataracts
acoustic neuroma
Schwann cell-derived tumours that commonly arise from the vestibular portion of the eight cranial nerve.
Bilateral cases in NF2
schwannomatosis
multiple tender cutaneous schwannomas w/o bilateral vestibular schwannomas that are characteristic of NF2
indistinguishable from mosaic NF2 - where vestibular schwannomas absent too, except by genetic analysis of biopsy
large tumour load, assessible by whole body MRI
Mutations in the tumour suppressor genes SMARCB1 and LZTR1and spontaneous NF2 mutations
aetiology of neurofibromatoiss
mutations on tumour suppressor genes
aetiology of T1 neurofibromatosis
mutations in NF1 gene - chromosome 17q11.2, encodes neurofibromin (a GTPase activating protein) = excessive activity of protoonchogene p21-ras
expression of NF1 is variable - even in family
Severe crush trauma can lead to the development of localised neurofibromas in patients with NF1
aetiology of T2 neurofibromatosis
mutation in NF2 gene - chr 22q11 - encodes merlin (or schwannomin)
50% are de novo mutations
mosaicism in some
epidemiology of neurofibromatosis
incidence 1 in 3000 births NF1 and 1 in 40000 for NF2
prevalence 1 in 2500 NF1 and 1 in 35000 NF2
sx of T1 neurofibromatosis
+ve FH, but 50% are new mutations
- skin lesions - Cafe-au-lait spots: flat, coffee-coloured patches of skin seen in 1st yr of life (clearest in UV), increasing in size and no with age. Adults have >=6 >15mm across. Do not predispose to skin cancer
- learning difficulties in 40%
- headaches
- disturbed vision - opyic glioma in 15%
- precocious puberty - lesions of pituitary from optic glioma invading chiasm
sx of t2 neurofibromatosis
+ve FH, but 50% are new mutations
hearing loss
tinnitus
balance problems
headache
facial pain or numbness
sx of acoustic neuroma
- symptoms of cranial nerve compression by tumour:
- VIII nerve: Hearing loss (95%), tinnitus and unsteadiness while walking.
- V nerve: Facial numbness, paraesthesia and pain (17%).
- VII nerve: Facial weakness (6%).
- With tumour progression (expansion into the cerebellopontine angle):
- Compression of the cerebellum resulting in ataxia.
- Compression of the lower cranial nerves (IX, X and XI) resulting in dysarthria and dysphagia.
signs of t1 neurofibromatosis
>5cafe au lait macules of>5 mm (pre-pubertal individuals) or>15 mm (post-pubertal individuals - flat, coffee-coloured patches of skin seen in 1st yr of life (clearest in UV), increasing in size and no with age. Adults have >=6 >15mm across. Do not predispose to skin cancer
neurofibromas (appear as cutaenous nodules/complex plexiform neuromas) -
dermal neurofibromas: small violaceous nodiles, gelatinous in texture, appear at puberty, may become papillomatous - not painful but may itch. Numbers increase with age
nodular neurofibromas: arise from nerve trunks, firm and clearly demarcated, cvan give rise to paraesthesiae if pressed
freckling in armpit/groin/neck base/submammary area - present by 10yrs
Lisch nodules - hamartomas on iris (use a slit lamp), harmless regular brown/translucent mounds, <=2mm in diameter
spinal scoliosis
short stature
microcephaly
signs of t2 neurofibromatoiss
few or no skin lesions - cafe-au-lait spots fewer than in NF1
sensineural deafness with facial nerve palsy or cerebellar signs if schwannoma is large
bilateral vestibular schwannomas (=acoustic neuromas) are characteristic, becoming symptomatic by 20yrs - sensineural hearing loss is 1st sign. Tinnitus, vertigo
- rate of tumour growth is unpredictable and variable
- tumours benign but cause problems by pressing on structures and increasing ICP
- tumours may be abscent in mosaic NF2
juvenile posterior subscapular lenticular opacity - a form of cataract, occurs before other manifestations and can be useful in screening those at risk
signs of acoustic neuroma
Abnormal cranial nerve examination:
VIII nerve: Hearing loss, the Weber and Rinne tests suggest asymmetric sensorineural hearing impairment, nystagmus (beating away from tumour).
V nerve: Loss of corneal reflex, facial numbness.
VII nerve: Lower motor neuron facial palsy.
Cerebellar compression: Ipsilateral ataxia and nystagmus.
Look for signs of neurofibromatosis.
Ix for neurofibromatosis
ophthalmological assessment
audiometry
MRI brain and spinal cord - For vestibular schwannomas, meningiomas and nerve root neurofibromas.
skull XR - sphenoid dysplasia in type 1NF
genetic testing - possible, but difficult because NF1 is long
hearing test from puberty in affected families
clear scan at 30 (unless FH of late onset) indicates gene hasnt been inherited
normal MRI in late teens helpful in assessing risk of passing onto offspring
diagnostic criteria for neurofibromatosis 1
if 2 of following:
- >=6 cafe-au-lair >5mm pre-pubertal or >15 post
- >=2 neurofibromas of any type or 1 plexiform
- freckling in axillary or inguinal regions
- optic glaucoma
- >-2 lisch nodules
- distinctive osseous lesion typical of NF1 eg sphenoid dysplasia
- 1st degree relative with NF1
dx criteria for neurofibromatosis 2
if either of following
- bilateral vestibular schwannoma on MRI or CT
- 1st degree relative with NF2 and - unilateral vestibular schwannoma OR one of neurofibroma, meningoma, glioma, schwannoma, juvenile cataract (NF2 type)
differentials for neurofibromatosis
NF1 differential - McCune-Albright syndrome, multiple lentigines, urticaria pigmentosa
NF2 differential - NF1, schwannomatosis
causes of cafe-au-lait spots
normal up to 5
NF1 - increased melanocyte density vs normal cafe-au-lait
NF2
rare syndrome - gaucher’s, McCune-Albright, Russell-Silver, tuberous sclerosis, Wiskott-Aldrich
mx of neurofibromatosis
no cure
if neurofibromas are large and painful -> cut out = reduce ca risk
plastic surgery
genetic counselling - withdrawn from society
