neurocutaneous syndromes Flashcards
neurocutaneous syndrome
NMS = brain and skin
group of cns disorders that have concurrent lesions in the eye + skin + visceral organs
phakotomoses = tumour of lense
neruomuctuateous syndrome
congenital malformation affecting nervous system , retina , eyeball retina + visceral organs are involved
examples of neurocutaneous syndrome
neurofibromatosis 1
tuberscloris sclerosis
sturge webber syndrome
ataxia telengastivia
why do u get neuromusctaneoous
skin and cns both originate from ectoderm
echo (outer)
meso and endo (inner) ]
echo differentiates into cns tooth enamel , epidermis , pigment cells , hair and swear cells , eyes mouth epithelium and facial cartilage
what are other associations of neuromuctaenous syndromes
mesoderm and endodermal structures can also be involved
e.g. visceral organs
tumours are often part of the syndrome (being and malignant)
causes of neruomuctaneous syndromes
congenital
genetics
autosominla dominant
autosom recessive
x link recessive
genetic abnomrlaity leads to embryological development
loss of tumour suppressor gene function
loss of gene associated with DNA repari
how are they diagnosed
clinical features
skin
family history clinical criteria
investigations
mir
biopsies
molecular genetics
common Neuro signs of neuro muctaneoous syndromes
seizures
developmental delay
abnormal head size
motor disorders
common skin features
birthmarks
lumps and bumps
common opthalmoological features
vis impairment
squint
proptosis
nystagmus
neurofibromatosis chromosome features
type 1 - von Recklinghausen
autosominal dominant , 50% new mutationsn
chromosome 17
type 2
autosomal dominant
chromosome 22
diagnostic criteria for nf1
ages 2 or more
diagnostic criteria
6 or more cafe au last spots
More than 2 neurofibromas or 1 plexiform neurofibroma
Axillary or Inguinal freckling
Optic glioma
>2 iris hamartomas(Lisch nodules)
Osseous lesions(spenoid wing dysplasia, thinning of long bone)
First degree relative with NF1
Diagnostic criteria usually sensitive by age 10
Size of café au lait spots > 5mm pre pubertal, >15mm post pubertal
Neurofibroma- painless soft nodules under the skin- benign nerve sheath tumour. Appear in adolescence(arise from Schwann cells)
Plexiform neurofibroma-associated with mutiple nerve bundles. Common in childhood. Eyes, face, trunk, limbs. 5-10% undergo malignant change
Optic glioma- low grade tumour of optic nerve
Hamartoma- benign proliferation of cells in sites of the body- growing in disorganised manner, but at same rate
Sphenoid bone just anterior to temporal bone- side of face
other features of NF1
Minor features
Macrocephaly
Short stature
Hypsarrythmia
Learning difficulties(60%)
Epilepsy
Hypertension(coarctation, renal artery stenosis, phaechromocytoma)
NF - tumour risk
Optic gliomas- 20%
Other gliomas(brainstem)
Ependymoma, meningioma, medulloblastoma
Wilms tumour
Rhabdomyosarcoma
Leukaemia
Melanoma
Medullary thyroid carcinoma
Phaeochromocytoma
Management of NF1
Essentially regular surveillance
Skin
Neurological examination
Opthalmology
Growth
BP
?Scans
Educational support
Intervention for specific issues
Surgery
Family genetic counselling
nf2 features
usually presents after puberty with hearing problems
may present younger with visual problems
NF2 diagnostic criteria
1 of :
bilateral vestibular nerve schwannoma
first degree relative with NF2 and either of in the patient
unilateral vestibular schwannoma
2 of the following
neurofibroma
glioma
shcwannoma
juvenile posterior subcapsular cataract
or 2 of
multiple meningiomas
unilateral vestibular nerve schwannoma
neurofibroma glioma
, scwannoma ,m juvenile posterior sub capsular catarxat
tuberous sclerosis
autosomonal dominant
1:20,000
Autosomal dominant
TSC1 mutation chromosome 9
TSC2 mutation chromosome 16
2/3rd spontaneous mutation
Usually present with seizures
60% have learning disability
Diagnostic criteria:
2 major and 1 minor OR 1 major and 2 minor
diagnostic criteria of tuberous slceorisis
Adenoma sebaceum
Periungal fibromas(after adolescence)
3 or more hypomelanotic patches
Shagreen patch
Multiple retinal hamartomas
Cortical tubers
Subependymal nodules
SEGA
Cardiac rhabdomyoma
Lymphangiomyomatosis(girls)
Renal angiomyolipoma
retinal harmotoma on a fundus look like
a fat glowing yellow spot
minor feature of tuberous scleorsis
Dental enamel pits
Bone cysts
Gingival fibromas
Non renal hamartomas
Renal achromatic patch
Confetti skin lesions
Multiple renal cysts
Macrocephaly
Cerebral white matter radial migration lines
management of tuberous scelorisis
Seizure management
Surgery for SEGA/Tubers
Evorolimus(mTor inhibitor)
SEGA
Renal angiomyolipomas
?Seizures
Surveillance
BP
Vision
Development
Genetic counselling
characteristics of sturge webber
1 in 20,000-1 in 50,000
Congenital disorder involving brain, skin and eye
Port wine stain at birth
Usually develop early focal seizures
Range of long term difficulties
Clinical features:
Seizures
Hemiplegia
Hemiatrophy
Learning difficulties
Skeletal lesions
Dental abnormalities
diagnostic criteria for for sturge webber syndrome
2 out of 3 of:
Facial port wine stain in V1 distribution of trigeminal nerve
Increased ocular pressure
Ipsilateral leptomeningeal angioma
eye features of sturge webber
Glaucoma
Bupthalmos
Iris heterochromia
Optic atrophy
ataxia chromosome
tenglanticatsia features
1:40,000
Autosomal recessive, or sporadic mutation
Chromosome 11
Absent/malfunctioning ATM protein
clinical features of ataxia tenglastia
Present with ataxia
Slowly progressive
Dystonia
Dysarthria
Later
Choreoathetosis, oculomotor, apraxia, nystagmus
Later development of telangiectasia
Increased susceptibility to respiratory infections
Intelligence preserved until later
other features of ataxia telangiastia
Short stature
Absent lymphoid tissue
Raised AFP, raised carcinogenic antigen
Glucose intolerance
MRI
Atrophy of cerebellum
Atrophy of posterior columns
Risk of neoplasm
Leukaemia, lymphoma, Hodgkins
Can die in early teens, many survive into adulthood
Importance of the Eye
Often gives clue to diagnosis
Part of diagnostic criteria
Eye problems can develop so need carefully monitoring
Need to know what you are looking for
Need to know importance of certain eye signs
Refer for neurological opinion
Other systems may be involved
May need involvement of visually impaired services
neuromuctaneous disorders are ….
congenital disorders with a genetic basis involving skin, eyes brain and often other organs
