2. INTRODUCTION
• Neurocutaneous syndromes are a
heterogenous group of disorders
• These involve the integument and the CNS
• These are mostly familial
• Arise due to a defect in differentiation of the
primitive ectoderm
3. 1. NEUROFIBROMATOSIS
2. TUBEROUS SCLEROSIS
3. STURGE WEBER SYNDROME
4. INCONTINENTIA PIGMENTI
5. ATAXIA TELANGIECTASIA
6. LINEAR NAEVUS SYNDROME
7. HYPOMELANOSIS OF ITO
8. VON HIPPEL LINDAU SYNDROME
4. NEUROFIBROMATOSIS
(VON RECKLINGHAUSEN’S DISEASE)
• It is an autosomal dominant disease
• It is protean, progressive
• It is a consequence of an abnormality of
neural crest differentitiation and migration
during early stages of embryogenesis
• It is of distinctintly 2 types:NF1 and NF2
5. NF1
• Incidence of 1 per 14000
• Majority of mutations occur from paternal
germline
• chromosome17q11
• Diagnosed when any 2 of the following 7 signs
are positive
1. 6 or more café au lait spots
2. Axillary or inguinal freckling
6. 3. 2 or more lisch nodules
4. 2 or more neurofibromatosis or 1 plexiform
neurofibromatosis
5. Osseous lesion : sphenoid dysplasia or
cortical thinning of long bones or scoliosis
6. Optic gliomas
7. First degree relative diagnosed by above
criteria
13. • MRI:
Abnormal hyperintense T2 weighted signals in
optic tracts, brain stem, globus pallidus,
thalamus, internal capsule, cerebellum
Called as UBOs
Represent areas of dysmyelination or increased
water content
14. NF2
• INCIDENCE OF 1 IN 50000
• Gene for NF2 located near long arm of 22q1
• Diagnosed when 1 of the following 2 criteria is
positive
15. 1. Bilateral accoustic neuromas
2. First degree relative with
• Unilteral eighth nerve mass
• Any 2 of
Neurofibroma
Meningioma
Glioma
Schwannoma
Posterior subcapsular lenticular opacities
16. TREATMENT
• No specific treatment available
• Ophthalmologic follow up essential
• Genetic counselling
• Examination of fetal DNA
17. TUBEROUS SCLEROSIS
• Autosomal dominant
• Prevalance of 1 in 6000
• 2 foci for the TS complex:
TSC1– on 9q - encoding a protein called
hamartin
TCS2 – on 16p – encoding a protein called
tuberin
18. DIAGNOSIS
• 2 major criteria or 1 major and 2 minor
criteria
• Major:
Skin lesions
Brain and eye lesions
Tumours of heart , kidneys or lungs
25. Cortical tuber
• Located in the convolutions of the cerebral
hemispheres and in the subependymal region
where it projects into the ventricular cavity
• May calcify and have a candle dripping
appearance
• CT and MRI identify them
26.
27. • Other CNS manifestations include seizures,
cognitive impairment and behavioral
abnormalities
32. STURGE WEBER SYNDROME
• Sporadic disorder
• Frequency of about 1 in 50000 live births
• Etiology
Anomalous development of primordial vascular
bed in early stages of cerebral vascularization
Overlying meninges are richly vascularized
Cortex atrophied and calcified
33. CLINICAL FEATURES
• Facial naevus:
Involves upper face and eyelid always
Complications may include buphthalmos and
glaucoma
• Seizures:
Focal tonic clonic
Contralateral to site of naevus
39. VON HIPPEL LINDAU SYNDROME
• Autosomal dominant
• Its focus is on chromosome 3p25 with a
defect occuring in VHL tumour suppressor
gene
• Incidence is 1 in 36000
40. CLINICAL FEATURES
• Cerebellar hemangioblastomas
It occurs mainly in early adult life
It has increased intracranial pressure signs
• Spinal cord hemangioblastomas
Disturbances in propioception , gait , bladder
function
41. • Retinal angiomas
Occur in about 25% of cerebellar
haemangioblastoma cases
Small masses of thin walled capillaries
Located in peripheal retina
Vision unaffected till late
Complications include retinal detachment
44. INCONTINENTIA PIGMENTI
(BLOCH SCHULBERGER SYNDROME)
• Rare , heritable, multisystem ectodermal
disorder
• Phenotype is produced by functional
mosaicism caused by random X inactivation of
an X linked dominant gene that is lethal in
males
• IKK-gama/NEMO gene
• Have mainly skin , dental , ocular
manifestations
45. DIAGNOSIS
• Major criteria:
1. Typical neonatal vesicular rash with
eosinophilia
2. Blaschkoid hyperpigmentation of trunk
3. Linear atrophic hairless lesions
46. • Minor criteria
1. Dental features
2. Alopecia , wooly hair
3. Abnormal nails
4. Multiple male miscarriages
47. SKIN MANIFESTATIONS
Has 4 phases
1. Phase 1 (vesicular)
Presents at birth or after a few weeks of life
Linear erythematous streaks and plaques of
vesicles
Has blood eosinophilia of upto 65%
Resolves by 4 months of age
48. 2. Phase 2 (verrucous)
Blisters resolve and form hyperkeratotic
verrucous plaques
Affect extremities
Involute by 6 months
49. • Phase 3 (pigmentary)
Characteristic of IP
Generally do not correlate with stage 1 and 2
areas
Seen within first few weeks of life
Mainly affect axilla , groin
Macular whorls, reticular patches , flecks – these
follow Blascko lines
50. Persist throughout childhood
Generally disappear by 16 years of life
Histological appearance – vacuolar degeneration
of epidermal basal cells and melanin in
macrophages of upper dermis
51. • Phase 4
Hypopigmented , anhydrotic , hairless patches
Mainly on flexor aspect of lower limbs
55. TREATMENT
• Depend on appearance of non cutaneous
manifestations as the cutaneous
manifestations are benign
• Genetic counselling
56. HYPOMELANOSIS OF ITO
(INCONTINENTIA PIGMENTI
ACHROMIANS)
• There is no evidence of genetic transmission
• It affects both sexes equally
• It should be differentiated from fourth stage
of IP
57. CLINICAL FEATURES
• Occurs within 2 years of age
• Hypopigmented macules all over body
• It remains througout childhood and fades in
adults
