neurocutaneous syndromes

Question 1

neurocutaneous syndrome

Answer 1

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

Question 2

examples of neurocutaneous syndrome

Answer 2

neurofibromatosis 1

tuberscloris sclerosis

sturge webber syndrome

ataxia telengastivia

Question 3

why do u get neuromusctaneoous

Answer 3

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

Question 4

what are other associations of neuromuctaenous syndromes

Answer 4

mesoderm and endodermal structures can also be involved

e.g. visceral organs

tumours are often part of the syndrome (being and malignant)

Question 5

causes of neruomuctaneous syndromes

Answer 5

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

Question 6

how are they diagnosed

Answer 6

clinical features

skin

family history clinical criteria

investigations

mir

biopsies

molecular genetics

Question 7

common Neuro signs of neuro muctaneoous syndromes

Answer 7

seizures

developmental delay

abnormal head size

motor disorders

Question 8

common skin features

Answer 8

birthmarks

lumps and bumps

Question 9

common opthalmoological features

Answer 9

vis impairment

squint

proptosis

nystagmus

Question 10

neurofibromatosis chromosome features

Answer 10

type 1 - von Recklinghausen

autosominal dominant , 50% new mutationsn

chromosome 17

type 2

autosomal dominant

chromosome 22

Question 11

diagnostic criteria for nf1

Answer 11

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

Question 12

other features of NF1

Answer 12

Minor features
Macrocephaly
Short stature
Hypsarrythmia
Learning difficulties(60%)
Epilepsy
Hypertension(coarctation, renal artery stenosis, phaechromocytoma)

Question 13

NF - tumour risk

Answer 13

Optic gliomas- 20%
Other gliomas(brainstem)
Ependymoma, meningioma, medulloblastoma
Wilms tumour
Rhabdomyosarcoma
Leukaemia
Melanoma
Medullary thyroid carcinoma
Phaeochromocytoma

Question 14

Management of NF1

Answer 14

Essentially regular surveillance
Skin
Neurological examination
Opthalmology
Growth
BP
?Scans
Educational support
Intervention for specific issues
Surgery
Family genetic counselling

Question 15

nf2 features

Answer 15

usually presents after puberty with hearing problems

may present younger with visual problems

Question 16

NF2 diagnostic criteria

Answer 16

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

Question 17

tuberous sclerosis

Answer 17

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

Question 18

diagnostic criteria of tuberous slceorisis

Answer 18

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

Question 19

retinal harmotoma on a fundus look like

Answer 19

a fat glowing yellow spot

Question 20

minor feature of tuberous scleorsis

Answer 20

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

Question 21

management of tuberous scelorisis

Answer 21

Seizure management
Surgery for SEGA/Tubers
Evorolimus(mTor inhibitor)
SEGA
Renal angiomyolipomas
?Seizures
Surveillance
BP
Vision
Development
Genetic counselling

Question 22

characteristics of sturge webber

Answer 22

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

Question 23

diagnostic criteria for for sturge webber syndrome

Answer 23

2 out of 3 of:
Facial port wine stain in V1 distribution of trigeminal nerve
Increased ocular pressure
Ipsilateral leptomeningeal angioma

Question 24

eye features of sturge webber

Answer 24

Glaucoma
Bupthalmos
Iris heterochromia
Optic atrophy

Question 25

ataxia chromosome
tenglanticatsia features

Answer 25

1:40,000
Autosomal recessive, or sporadic mutation
Chromosome 11
Absent/malfunctioning ATM protein

Question 26

clinical features of ataxia tenglastia

Answer 26

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

Question 27

other features of ataxia telangiastia

Answer 27

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

Question 28

Importance of the Eye

Answer 28

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

Question 29

neuromuctaneous disorders are ….

Answer 29

congenital disorders with a genetic basis involving skin, eyes brain and often other organs