Neurocutaneous Markers and Congenital malformations - Dr. S. Srinivasan, Professor of Pediatrics,...
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Transcript of Neurocutaneous Markers and Congenital malformations - Dr. S. Srinivasan, Professor of Pediatrics,...
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
Neurocutaneous syndromes
Remember the Following 3 Basic POINTS
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
Neurocutaneous syndromes
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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 & CLINICAL NEUROCUTANEOUS SYNDROMES -MGMCRI- 8
th&9
thSemesters 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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
Tuberous Sclerosis –
Clinical Features
Skin Features in Tuberous
Sclerosis
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
ADENOMA SEBACEUM (Facial
Angiofibromas)
Shagreen’s patches
Tuberous Sclerosis
ADENOMA SEBACEUM
(Facial Angiofibromas)
Forehead Plaque
Tuberous Sclerosis
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
Café – au – lait spots or patches
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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%
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
Early recognition of TS
• Neuroimaging studies
• EEG
• ECG
• Cardiac, Chest & Renal
ultrasonography
• Chest CT
VITAL TO PREVENT
SERIOUS CLINICAL CONSEQUENCES.
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
Commonest of the 2 types
Incidence: 1 in 3000
Implicated gene in Ch17
Neurofibromin – Encoded Protein
Neurofibromatosis-1 (NF-1)
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
Complications in
Neurofibromatosis-1 (NF-1)
Seizures
Macrocephaly
Hydrocephalus
Learning, Behavioural & Speech
Disabilities,ADHD
Moya-Moya Disease
Precocious Puberty
Systemic Hypertension: Fibromuscular
Dysplasia, Phaeochromocytoma
Malignancies:
N.Fibrosarcomas; Malignant Schwanomas
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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)
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
STURGE –WEBER SYNDROME
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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)
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
Major neurologic features
Cerebellar & Spinal Cord
hemangioblastomas
Retinal Angiomas (25%)
Cystic lesions: Kidneys,
Pancreas, Liver and Epididymis
Pheochromocytoma: Common
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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.
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
Incontinentia Pigmenti (IP)
('Bloch-Sulzberger syndrome' )
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
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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
Incontinentia Pigmenti (IP)
('Bloch-Sulzberger syndrome' )
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
ATAXIA-TELANGIECTASIA
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
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.
NEUROCUTANEOUS SYNDROMES -MGMCRI- 8th
&9th
Semesters MBBS-UG PEDIATRICS Theory Lecture
31 mar 16
ATAXIA-TELANGIECTASIA