1. NEUROCUTANEOUS
SYNDROME
DR. PANKAJ BAJAJ
1ST YEAR DNB PEDIATRIC
J.L.N.Hospital & Research Centre, Bhilai Steel Plant
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2. TOPICS TO BE
COVERED……….
DEFINITION
CLASSIFICATION
DETAILS OF EACH NEURO
CUTANEOUS SYNDROME
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3. DEFINITION
The neurocutaneous syndromes include a
Heterogeneous group of disorders
Characterized by abnormalities of both the
Integument and central nervous system
(CNS).
Most disorders are familial and believed to
Arise from a defect in differentiation of the
Primitive ectoderm.
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4. CLASSIFICATION
Disorders classified as neurocutaneous syndromes
Include
Neurofibromatosis
Tuberous Sclerosis
Sturge-Weber Syndrome
Von Hippel–Lindau Disease
PHACE Syndrome
Ataxia Telangiectasia
linear Nevus Syndrome
Hypomelanosis of Ito NST
LP
Incontinentia Pigmenti HINT
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5. NEUROFIBROMATOSIS
Neurofibromatosis are autosomal dominant
Disorders that cause tumors to grow on
Nerves and result in other abnormalities
such As skin changes and bone deformities
Neurofibromatosis 1 (NF-1)
Neurofibromatosis 2 (NF-2)
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6. NEUROFIBROMATOSIS 1
(NF-1)
Most prevalent type
Incidence of 1/3,000
Autosomal dominant disorder
Over half the cases are sporadic,representing
De novo mutations.
Chromosome region 17q11.2
Encodes a protein also known as
Neurofibromin.
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7. It is diagnosed when any 2 of the following 7 features Are
present:
(1) Six or more Cafe-au-lait macules
(2) Axillary or inguinal freckling .
(3) Two or more iris Lisch nodules
(4) Two or more neurofibromas
or 1 plexiform neurofibroma.
(5) A distinctive osseous lesion such as
Sphenoid dysplasia.
(6) Optic gliomas low-grade astrocytomas.
(7) A first-degree relative with NF-1.
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8. Cafe-au-lait macules
• Over 5 mm in greatest diameter in prepubertal individuals.
• Over 15 mm in greatest diameter in postpubertal individuals.
• Hallmark of neurofibromatosis almost 100% of patients.
• Present at birth but increase in size, number, and pigmentation, especially during
The first few yrs of life.
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• Predilection for the trunk and extremities but sparing the face.
9. Axillary or inguinal freckling
• Multiple hyperpigmented areas 2-3 mm in diameter.
• Skinfold freckling usually appears between 3 and 5 yr of age.
• Frequency greater than 80% by 6 yr of age.
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10. Two or more iris Lisch nodules
• Hamartomas.
• located within the iris .
• Best identified by a slit-lamp examination.
• They are present in >74% of patients with NF-1 but are not a component of NF-2.
• The prevalence increases with age.
• Only 5% of children <3 yr of age.
• 42% among children 3-4 yr of age. JLNH & RC
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• 100% of adults ≥21 yr of age.
11. Two or more neurofibromas or 1 plexiform
neurofibroma
• SITES involve the skin, peripheral nerves and blood vessels, viscera .
• Hormonal influence.
• They are usually small, rubbery lesions with a slight purplish discoloration of the
overlying skin.
• Plexiform neurofibromas are usually evident at birth and result from diffuse
thickening of nerve trunks that are frequently located in the orbital or temporal region
of the face.
• The skin overlying a plexiform neurofibroma may be hyperpigmented to a greater
degree than a Cafe-au-lait spot.
• Plexiform neurofibromas may produce overgrowth of an extremity and a deformity of
the 5/30/2012
corresponding bone. JLNH & RC 11
13. • Scoliosis is Most Common Orthopedic manifestation- Not specific for
diagnostic criterion
• Cortical thining of long bones with or without pseudoarthrosis.
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14. Optic Gliomas
represent mostly low-grade Astrocytomas
• it is recommended that all children age 10 yr or younger with NF-1 undergo annual
ophthalmologic examinations.
•When they enlarge and put pressure on the optic nerves and chiasm resulting in
impaired visual acuity and visual fields.
• Extension into the hypothalamus can lead to endocrine deficiencies or failure to thrive.
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15. •The MRI findings of an optic glioma include diffuse thickening, localized enlargement, or a
distinct focal mass originating from the optic nerve or chiasm
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16. •A first-degree relative with NF-1 whose diagnosis was based on the aforementioned
criteria.
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18. NEUROFIBROMATOSIS 2
(NF-2)
Rarer condition
Incidence of 1/25,000
The NF2 gene (also known as merlin or
Schwannomin)
located on chromosome 22q1.11
Cafe-au-lait spots and skin neurofibromas are
less common in NF-2
Posterior subcapsular lens opacities are
identified In about 50% of patients with NF-2
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19. May be diagnosed when 1 of the following
4 Features is present:
(1) bilateral vestibular schwannomas
(2) a parent, sibling, or child with NF-2 and
Either unilateral vestibular schwannoma or
Any 2 of the following:
meningioma, Schwannoma, glioma, neurofi
broma, or Posterior subcapsular lenticular
opacities.
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20. (3) unilateral vestibular schwannoma and
any 2 of the following:
meningioma, schwannoma, Glioma, neurofi
broma, or posterior Subcapsular lenticular
opacities.
(4) multiple meningiomas (2 or more) and
Unilateral vestibular schwannoma or any 2
of The following:
schwannoma, glioma, Neurofibroma or
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21. Bilateral Acoustic Neuromas
•Hearing loss
•Unsteadiness
•Headache
•Facial weakness
•More commonly in 2nd and 3rd decade.
Subcapsular opacity- 50% of the cases of NF-
II
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23. Treatment and Management of
NF-I and NF-II
• Genetic counseling • Tests should be
• Half result from ordered if positive
fresh Mutation physical findings are
• Prenatal diagnosis in present
familial cases. • Annual evaluation
– By pediatrician
– By pediatric
ophthalmologist
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24. Tuberous Sclerosis
TSC is an extremely heterogeneous disease
With a wide clinical spectrum varying from
Severe mental retardation and
incapacitating Seizures to normal
intelligence and a lack of Seizures, often
within the same family. The Disease affects
many organ systems other Than the skin
and brain, including the
heart, Kidney, eyes, lungs, and bone.
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25. Autosomal dominant trait with variable
Expression.
Prevalence of 1/6,000 newborns.
Spontaneous genetic mutations occur in 2/3 of the
Cases.
Molecular genetic studies have identified 2 foci
For TSC
GENE LOCATION ENCODES
TSC1 gene Chromosome9q34 Protein called
hamartin
TSC2 gene Chromosome16p13 the protein tuberin
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26. The TSC1 and TSC2 genes are tumor
suppressor Genes.
Both are involved in a key pathway in the cell
that Regulates protein synthesis and cell size.
The loss Of either tuberin or hamartin results
in the Formation of numerous benign tumors
(Hamartomas)
Definite TSC is diagnosed when at least 2
major Or 1 major plus 2 minor features are
present
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27. MAJOR FEATURES OF TUBEROUS SCLEROSIS
COMPLEX
Cortical tuber
Subependymal nodule
Subependymal giant cell astrocytoma
Facial angiofibroma or forehead plaque
Ungual or periungual fibroma (nontraumatic)
Hypomelanotic macules (>3)
Shagreen patch
Multiple retinal hamartomas
Cardiac rhabdomyoma
Renal angiomyolipoma
Pulmonary lymphangioleiomyomatosis
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28. MINOR FEATURES OF TUBEROUS
SCLEROSIS COMPLEX
Cerebral white matter migration lines
Multiple dental pits
Gingival fibromas
Bone cysts
Retinal achromatic patch
Confetti skin lesions
Nonrenal hamartomas
Multiple renal cysts
Hamartomatous rectal polyps
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29. Ash leaf skin lesions
at least 3 hypomelanotic macules must be
present
• Hypopigmented in 90% of patients
• Enhanced by wood’s lamp examination
• At least 3 hypomelanotic macules must
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be present 29
30. Retinal lesions
• Mulberry Tumors
• Retina Nerve fiber
and undifferentiated
glial tissue
• 1/3 to ½ patients
• Can also be found in
Neurofibromatosis
and Normal persons.
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31. Tuberous Sclerosis
Sebaceous adenomas –Facial Angiofibroma– 8-10 .
by adolescence fully developed Forehead Plaque.
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32. Shagreen patch
• Roughened, raised lesion with an
Orange-peel consistency located
Primarily in the lumbosacral region
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http://www.massgeneral.org/livingwithtsc/affects/skin.htm 32
39. kidneys angiomyolipomas
The current recommendation is to follow
Them by yearly imaging, and when the
lesion Becomes larger than 4 cm, to use
Transcatheter Tumor embolization for
treatment
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40. ROUTINE FOLLOW-UP
Physical examination:
Brain MRI every 1-3 yr,
Renal imaging (ultrasound, CT, or MRI)
every 1-3 yr
Neurodevelopmental testing at the time of
Beginning 1st grade.
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41. Sturge-Weber Syndrome
Sturge-Weber syndrome (SWS) is a
sporadic Vascular disorder and consists of a
Constellation of symptoms and signs
including A facial capillary malformation
(port-wine Stain), abnormal blood vessels
of the brain (leptomeningeal angioma), and
abnormal Blood vessels of the eye leading
to glaucoma.
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42. 1 per 50,000 live births have SWS.
Etiology remains unclear.
??Anomalous development of the
embryonic vascular bed in the early stages
of facial and cerebral development.
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43. Clinical Manifestations
The facial port-wine stain.
Overall incidence be 8-33%
The capillary malformation.
Buphthalmos and glaucoma
Transient strokelike episodes or visual
defects Result From thrombosis of cortical
veins.
Mental retardation or severe learning
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Disabilities 50% In later childhood.
44. Unilateral, and always involves the upper face
And eyelid, in a distribution consistent with the
Ophthalmic division of the trigeminal nerve.
Port Wine Stain
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facial nevus
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46. Epilepsy
75-90%,1st yr of life.
Focal tonic-clonic and Contralateral to the
side Of the facial capillary Malformation.
Refractory to anticonvulsants associated
With A slowly progressive hemiparesis .
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47. Diagnosis
Based on the involvement of the brain and the
Face, there are 3 types according to the Roach
Scale:
1 Type I: Both facial and leptomeningeal
Angiomas; may have glaucoma
2 Type II: Facial angioma alone (no CNS
Involvement); may have glaucoma
3 Type III: Isolated leptomeningeal
angiomas; Usually no glaucoma
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50. Treatment
Symptomatic and multidisciplinary.
It is aimed at
Controlling seizures
Treating headaches
Preventing strokelike episodes
Monitoring for Glaucoma
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51. laser therapy for the cutaneous capillary
Malformations.
If the seizures are refractory to
anticonvulsant therapy Than consider
hemispherectomy.
Regular measurement of intraocular
pressure.
Pulsed dye laser therapy for port-wine
stain, ParticularlyJLNH & RC is located on the
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52. Von Hippel–Lindau Disease
Von Hippel–Lindau (VHL) disease affects
many Organs, including the
cerebellum, spinal
cord, Retina, kidney, pancreas, and
epididymis.
Incidence is around 1 : 36,000.
Autosomal dominant mutation affecting a
Tumor suppressor gene, VHL.
Chromosome 3q25. & RC
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53. Include cerebellar hemangioblastomas and
Retinal angiomas.
Cystic lesions of the
kidneys, pancreas, liver, And epididymis as
well as pheochromocytoma Are frequently
associated.
Renal carcinoma is the most common cause
of Death.
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54. Cerebellar Hemangioblastoma
Raised Intra Cranial
Pressure
Cystic cerebellar lesion
with a vascular mural
nodule- erythropoietin
like protein.
Spinal Cord-
abnormalities of
proprioception, disturba
nces of bladder control
and gait impairement.
http://www.cc.nih.gov/ccc/papers/vonhip/cnshemangioblastomas.html
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55. Retinal Angioma
Peripheral-Initially vision is
unaffected
Grow, bleed, leave serous
fluid-retinal detachment
Small-Laser photocoagulation
Large-Freezing probe from
outside the globe.
25% of retinal angioma
patients will have extraocular
manifestation
60% with nonocular
manifestations will have
Retinal Angioma.
http://www.kellogg.umich.edu/theeyeshaveit/congenital/retinal-
angioma.html
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56. PHACE/S Syndrome
Posterior fossa malformations
Hemangiomas
Arterial anomalies
Coaractation of the aorta
Eye abnormalities
+
Sternal clefting and/or a supraumbilical raphe
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57. Ataxia Telangiectasia
Ataxia telangiectasia (A-T) is a Progressive
Degenerative disease involving many major
body Systems.
It is an autosomal recessive disease.
A-T is usually noticed in the second year of
life as a Child develops problems with balance
and Slurred Speech caused by ataxia (lack of
muscle control).
The ataxia occurs because the cerebellum, the
part of The brain that controls muscle
movement, is Degenerating.
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58. Characterised by telangiectasia of
Conjunctiva, nose, ears and skin
creases.
About 70% of children with A-T also
have Immune system problems that
make Them more susceptible to
chronic URTI, lung infections, and
certain cancers, such As leukaemia
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59. Currently, there is no cure for A-T and no
way To stop its progression. But treatment
can help Kids manage symptoms.
Physical therapy and occupational therapy
may Help maintain flexibility.
Speech therapy can help address slurring
and Other speech problems.
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60. linear Nevus Syndrome
This sporadic condition is characterized by
a Facial nevus and neurodevelopmental
Abnormalities.
The nevus is located on the forehead and
nose And tends to be midline in its
distribution.
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61. 84%-Face
50%-Scalp, Neck and face
Scalp lesions devoid of hair
Seizures in 75%
› Infantile spasm
› Generalized Tonic
› Tonic Clonic
Neurological Deficits
› Cranial Nerve palsies
VI, VII
› Cortical Blindness
› Hemiparesis
(hemimegalencephaly)
Mental Retardation-in
young children upto70%
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63. Mosaicism-Family history is rare
Neurological Association
› Mental retardation (70%)
› Seizures (40%)
› Microcephaly(25%)
› Developmental delay
› Deafness
› Visual problems
› Headache
› Tooth or mouth problems
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64. Incontinentia Pigmenti
This heritable, multisystem ectodermal
disorder features dermatologic, dental, and
ocular abnormalities
Functional mosaicism
Random X-inactivation of an X-linked
dominant Gene (IKK-gamma/NEMO gene)
Lethal in Males
Xq28
Increased Frequency of spontaneous abortions.
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65. Stage I
• Erythematous linear
streaks and plaques
of vescicles
• DD-Herpes, bullous
impetigo, mastocytos
is
• eosinophilic
spogiosis
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• Resolve by 4 mo
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66. Stage II
• Verrucous plaques
• Dry and
hyperkeratotic
• Involute in 6 months
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67. Stage III
Hyperpigmentation
Hallmark
Macular whorls, linear
streaks
Lines of Blaschko.
Sites are not necessorily
same.
Invariably affects axilla
and groin
Fade by Early
adoleacence.
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68. Stage IV
• Hypopigmented
• Hairless
• Anhydrotic
• Usually lower legs.
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