Neurocutaneous Markers and Congenital malformations - Dr. S. Srinivasan, Professor of Pediatrics, MGMCRI

Neuro-Cutaneous Syndromes
in Children ( NCS )
MGMCRI-
8th& 9th Semesters MBBS- UG
Pediatrics Theory Lecture
31 mar 16
S.Srinivasan
Professor of Paediatrics
MGMCRI, Pillayarkuppam
Puducherry

Neurocutaneous Syndromes in Children ( NCS )
Learning Objectives
1. Define the term – “ Neurocutaneus Syndromes”
2. List three common types in NCS
3. Explain the reason of association between Skin and CNS
disorders
4. Recognize the cutaneous lesions; Explain or Correlate their
presence with the neurological disorders and Diagnose the
specific NCSyndrome
5. Tell the mode of genetic inheritance of the NCS
6. Enumerate salient clinical features ( Signs & Symptoms ) of
the most common NCS
7. List a few common complications of these conditions
8. Choose appropriate investigative work up
9. Outline briefly the management plan of the common NCS
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th&9th Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16

 Central Nervous System Disorders
with concurrent lesions in the
Skin, Eye,
and possibly
other Visceral Organs
Neurocutaneous syndromes
Refer to a heterogenous group of
31 mar 16

• The NeuroCutaneous ( Skin & CNS
manifestations are related to the
“ COMMON ECTODERMAL ORIGIN ” of
these organs
• Heredofamilial Disorder
• Defective differentiation of primitive
ectoderm
 Remember the Following 3 Basic POINTS
31 mar 16

• Tuberous Sclerosis
• Neurofibromatosis
• Sturge- weber Syndrome
• Incontinentia Pigmenti
• Hypomelanosis of Ito
• Ataxia Telangiectasia
• Von Hippel – Lindau Disease
• Linear Nevus Syndrome
• PHACE Syndrome
31 mar 16

31 mar 16
Plexiform Neurofibroma
Son and mother having NCS:
Eyelid skin Neurofibroma &
skin Neurofibromas

Tuberous Sclerosis
 Inherited ( Autosomal Dominant with “ NEAR
COMPLETE” penetrance ) Neuro - Cutaneous
disorder
 Characteric pleomorphic features involving
many organ systems, including multiple benign
neoplasms (hamartomas) of the brain, kidney,
and skin
 Nonfamilial cases ( spontaneous mutations or
mosaicism )
 2 TS genes- ch 9 & 16 (TSC1 & TSC2 genes)
and the other on chromosome 16 (gene)
PHYSICAL FINDINGS & CLINICALNEUROCUTANEOUS SYNDROMES -MGMCRI- 8th&9th Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16

 Dermatologic manifestations :
clues to the diagnosis
 Vogt’s Classic diagnostic triad
( Seizures, mental retardation, &
Facial Angiofibromas ) - <50%
 All clinical features of TS :
Not apparent in the first yr of life
31 mar 16
Tuberous Sclerosis –
Clinical Features

Skin Features in Tuberous
Sclerosis
31 mar 16
 Hypomelanotic ASH LEAF Macules
 Facial Angiofibromas (Adenoma
Sebaceum)
 Shagreen's patches
 Forehead Plaque
 Ungual Fibromas

Dermatologic manifestations in
children with Tuberous Sclerosis
Easiest and most accessible method
of establishing the diagnosis
31 mar 16

31 mar 16
ADENOMA SEBACEUM (Facial
Angiofibromas)
Shagreen’s patches
Tuberous Sclerosis

ADENOMA SEBACEUM
(Facial Angiofibromas)
Forehead Plaque
Tuberous Sclerosis

31 mar 16
Café – au – lait spots or patches

31 mar 16

Neurologic manifestations in
Children with TS
 Brain hamartomas:
- Cortical tubers
- Subependymal Nodules
- Subependymal Giant Cell Astrocytomas
 Intractable seizures -90% to 96% of TS
 Infantile spasms: Most common
 First epileptic episode in the first 2 yr of life in
85% of children
 Behavioral and cognitive dysfunction, including
autism and mental retardation: 40% to 50%
31 mar 16
 Leading cause of morbidity and mortality

Involvement of the other Organs in TS
Renal Angiomyolipoma
Pulmonary (1%
to 6%)
Lymphangiomyomatosis
(LAM), a progressive cystic
lung disease
Cardiovascular
(50 to 60 %)
Rhabdomyoma (most
common ) - - Primary
cardiac tumor in infants
and children;
80% to 95% of patients with cardiac
rhabdomyomas have TS
Ocular ( 40% to 50% ) Retinal Hamartomas
31 mar 16

Early recognition of TS
• Neuroimaging studies
• EEG
• ECG
• Cardiac, Chest & Renal
ultrasonography
• Chest CT
VITAL TO PREVENT
SERIOUS CLINICAL CONSEQUENCES.
31 mar 16

Neurofibromatosis- (NF)
• 2 Types: NF-1 & NF-2
• Inheritance of both types:
Autosomal Dominant
• Main features: Nerve tumors , Skin
changes seen as features/markers
with bone deformities
31 mar 16

Axillary Freckling
Iris :2 or more Lisch Nodules
2 or more
Neurofibromas
over the skin or
even 1 Plexiform
Neurofibroma
Sphenoid Dysplasia
Neurofibromatosis-1 (NF-1)
Classic features
31 mar 16

 Commonest of the 2 types
 Incidence: 1 in 3000
 Implicated gene in Ch17
 Neurofibromin – Encoded Protein
Few Basic known Facts

1) 6 or more Café –au – lait spots
2) Freckling in axillary or inguinal regoin
3) Lisch Nodules -2 or more seen over iris of the eyes
4) 2 or more Neurofibromas over the skin or even 1
Plexiform Neurofibroma
5) Distinctive Bone lesion – Sphenoid Dysplasia
6) Optic Gliomas –Low grade Astrocytomas
7) A first degree relative with NF -1
Diagnosis
 Presence of 2 / 7
31 mar 16

Complications in
 Seizures
 Macrocephaly
 Hydrocephalus
 Learning, Behavioural & Speech
Disabilities,ADHD
 Moya-Moya Disease
 Precocious Puberty
 Systemic Hypertension: Fibromuscular
Dysplasia, Phaeochromocytoma
 Malignancies:
N.Fibrosarcomas; Malignant Schwanomas
31 mar 16

 Rarer (1 in 25000)
 NF2 Gene (Merlin or Schwannomin )
 Gene: Ch 22q
 Less common : Café au lait spots &
Skin neurofibromas
 Eyes: 50% - Posterior Subcapsular
Cataracts / Lens opacities

Neurofibromatosis-Type2 (NF-2)
31 mar 16

Neurofibromatosis-Type2 (NF-2)
Diagnosis made –
Presence of any one of the following
1. Bilateral vestibular Schwannomas
2. Family ( parent, sibling or child with
NF-2)
a) unilateral vestibular schwannoma
or
b)Presence of any two of the following:
- Meningiomas, Schwannoma, Glioma,
Neurofibroma or Posterior Subcapsular
lenticular opacities
31 mar 16

STURGE –WEBER SYNDROME
31 mar 16

Sturge-Weber syndrome (SWS)
Sporadic vascular disorder
1 in 50,000 live births
Constellation of symptoms and signs
Facial port-wine stain capillary
malformation
Leptomeningeal angioma ( Abnormal
blood vessels of the brain )
Abnormal blood vessels of the choroid
of the eye →Buphthalmos (Glaucoma)
31 mar 16

31 mar 16
Hyperdense gyriform calcifications in left
parieto-occipital lobe with evidence of
moderate gyral enhancement
Nevus Flammeus Lt.Parietal Menin.
Haemangioma

Sturge-Weber syndrome
Port-wine stain involving
both V1 V2 dermatomes
CT scan- unilateral calcification &
atrophy of cerebral hemisphere
31 mar 16

Presenting Symptoms of Sturge –Weber
Syndrome ( SWS )
 Seizures ( 90% of children with SWS )
 Hemiparesis
 Stroke-like episodes
 Visual disturbances -Hemianopsia
 Headaches
 Developmental and Intellectual
delay
31 mar 16

Management of SWS
consists of anticonvulsants and surveillance for
complications including glaucoma, buphthalmos, and
behavioral abnormalities
Regular measurement of intraocular pressure
AIMS:
 Seizure control
 Treatmentof headaches, and
 Prevention of stroke-like episodes
 Monitoring of glaucoma and
 Pulsed-dye Laser therapy for the cutaneous capillary
malformation
 Surgery in selected refractory cases :
Hemispherectomy.
Symptomatic & Multidisciplinary Management

von Hippel-Lindau disease
1 in 36,000 newborns
Autosomal Dominant
Mutation affecting a tumor suppressor
gene, VHL
 Multiorgan involvement: Cerebellum,
spinal cord, retina, kidney, pancreas,
and epididymis
31 mar 16

Major neurologic features
Cerebellar & Spinal Cord
hemangioblastomas
Retinal Angiomas (25%)
Cystic lesions: Kidneys,
Pancreas, Liver and Epididymis
 Pheochromocytoma: Common
31 mar 16

 Skin : Earliest symptom
 Skin lesions may follow Blaschko lines
and their melanoblasts start to
transform into melanocytes after birth
 3 or 4 stages :- Vesicular, Verrucous,
Hyperpigmented, and sometimes
Hypopigmented stagemonths and
disappear within 6 months after birth.
31 mar 16
Incontinentia Pigmenti (IP)
('Bloch-Sulzberger syndrome' )

Rare (1 per 40,000) X-linked
genodermatosis
Mutation of NEMO/IKKr gene in X-
Chromosome
Occurs mostly in female infants
(95%)due to its fatality in male in
utero
31 mar 16

MGMCRI- 8th&9th Semesters MBBS-UG PEDIATRICS Theory Lecture 31 mar 16

Other Organs involved in IP
 Teeth: Delayed eruption of teeth, changes in dental
contour (circular or conical shape), and hypodontia
 Eyes (RETINOPATHY): Speckled diffuse
hypopigmentation in the retina, microphthalmia,
lenticular hemorrhage, retrolental fibroplasia, cataract,
and atrophy of the optic nerve
 CNS: seizure, microcephaly, mental retardation, and
spastic Paralysis
 Musculoskeletal, and Cardiovascular anomalies
31 mar 16

ATAXIA-TELANGIECTASIA
31 mar 16
Mutation of ATM Gene
Ataxia (12-25 months ), Nystagmus,
Chorea
Ocular Telangiectasia (2-7 years)
Chronic Sinopulmonary Infections
 Vitiligo

• GTT: abnormal
• Serum IgA & IgE : Decreased
• Alpha –Fetoprotein &
Carcinoembryogenic Antigen :
Elevated
• Chromosomal Breakages
• Neuroimaging: Cerebellar Atrophy
• Predisposition to Lymphoreticular
malignancies.
31 mar 16
ATAXIA-TELANGIECTASIA

Neurocutaneous Markers and Congenital malformations - Dr. S. Srinivasan, Professor of Pediatrics, MGMCRI

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Neurocutaneous Markers and Congenital malformations - Dr. S. Srinivasan, Professor of Pediatrics, MGMCRI