Neurocutaneous syndromes involve abnormalities of both the skin and central nervous system that are mostly inherited. Some key neurocutaneous syndromes discussed in the document include neurofibromatosis, tuberous sclerosis, Sturge Weber syndrome, incontinentia pigmenti, ataxia telangiectasia, linear nevus syndrome, hypomelanosis of Ito, and Von Hippel Lindau syndrome. They arise due to defects in ectodermal differentiation and have varied clinical manifestations affecting the skin, brain, eyes, and other organ systems. Treatment depends on the specific syndrome but may include seizure management, tumor treatment, and genetic counseling.

1. NEUROCUTANEOUS SYNDROMES

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

10. Clinical features
• Learning disabilities
• Attention deficits
• Psychosocial behavior disorder
• Speech disorder
• Seizures
• Macrocephaly

11. • Cerebral vessls – aneurysm or stenosis
• Hypertension
• Precocious puberty
• Neurofibroma differentiating into
neurofibrosarcoma or malignant schwannoma
• Increased incidence of tumours like
 Phaechromocytoma
 Wilms tumour
 Leukaemia
 rhabdomyosarcoma

12. • Increased CNS tumours like
 Meningiomas
 Optic gliomas
 Neurofibroma
 astrocytomas

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

19. • Minor:
Bone cysts
Rectal polyps
Dental enamel pits
Gingival fibromas
Nonrenal hamartomas
Confetti skin lesions
Multiple renal cysts

20. CLINICAL MANIFESTATIONS
• Skin lesions
1. Ash leaf macules
2. Shagreen patch
3. Sebacious angiomas (angiofibromas)
4. Subungual fibromas

24. • Retinal lesions
1. Mulberry tumours
2. Hamartomas

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

27. • Other CNS manifestations include seizures,
cognitive impairment and behavioral
abnormalities

28. • Heart:
Rhabdomyosarcomas – in 40% of TS
Cause CCF, or arrhythmias
• Lungs:
lymphangiomyomatosis

29. • Kidneys:
Angiomyolipomas
Renal cysts

30. DIAGNOSIS
• High index of suspicion clinically
• CT head or MRI may help
• Genetic testing for TSC1 and TSC2

31. TREATMENT
• There is no specific treatment

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

34. • Hemiparesis
• Mental retardation

35. DIAGNOSIS
• Skull Xray:
Rail-road apearance
• CT:
Unilateral cortical atrophy and ipsilateral
dilatation of lateral ventricle
• MRI

38. TREATMENT
• seizure management
• Management of buphthalmos and glaucoma

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

42. • Cystic lesions of kidney , pancreas , liver
• phaeochromocytomas

43. TREATMENT
• Regular follow up

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

53. OTHER CLINICAL MANIFESTATIONS
• Alopecia(40%)
• Dental(80%) – hypodontia , conical teeth ,
impaction
• CNS -- cognitive defects ,mental retardation ,
paralysis , spasticity , seizures , microcephaly
• Ocular(30%) -- neovascularization and retinal
detachment , microphthalmos , strabismus ,
optic nerve atrophy , cataracts

54. • Dystrophy of nails: ridging , pitting
• Skeletal malformations

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

58. OTHERS
• Mental retardation(70%)
• Seizures(40%)
• Microcephaly(25%)
• Hypotonia(15%)
• Scoliosis
• Strabismus , nystagmus

59. LINEAR NAEVUS
• Facial naevus:
Midline
Occurs on forehead and nose
Faint in infancy
Later hyperkeratotic
Yellow brown in colour

60. • Nervous system disorders:
Seizures
Mental retardation
Hemiparesis
Homonymous hemianopia

61. • CT shows hemimeganencephay with
hamartomatous changes

62. PHACE
• Posterior fossa malformations
• Hemangiomas
• Coarctation of aorta and cardiac defects
• Arterial malformations
• Eye

63. • Facial hemangioma ipsilateral to aortic arch
• Occurs more commonly in females

64. ATAXIA TELANGIECTASIA
• Autosomal recessive inheritance
• It occurs due to a mutation of ATM gene on
chromosome 11q 22-23

65. CLINICAL FEATURES
• Cerebellar ataxia
• Ocuucutaneous telengiectasias
• Chronic sinopulmonary disease
• Decreased elasticity of the skin
• Oculomotor apraxia of horizontal gaze,
nystagmus , strabismus
• Increased incidence of lymphoreticular tumours
like lyphomas, leukaemias , hodgkin’s disease

66. THANK
YOU!!!