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


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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


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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



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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


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31 mar 16

Tuberous Sclerosis –

Clinical Features

Skin Features in Tuberous

Sclerosis


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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


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ADENOMA SEBACEUM (Facial

Angiofibromas)

Shagreen’s patches

Tuberous Sclerosis

ADENOMA SEBACEUM

(Facial Angiofibromas)

Forehead Plaque

Tuberous Sclerosis


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Café – au – lait spots or patches


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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%


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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


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31 mar 16

Early recognition of TS

• Neuroimaging studies

• EEG

• ECG

• Cardiac, Chest & Renal

ultrasonography

• Chest CT

VITAL TO PREVENT

SERIOUS CLINICAL CONSEQUENCES.


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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


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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


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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


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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


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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)


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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


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STURGE –WEBER SYNDROME


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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)


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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


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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


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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


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Major neurologic features

Cerebellar & Spinal Cord

hemangioblastomas

Retinal Angiomas (25%)

Cystic lesions: Kidneys,

Pancreas, Liver and Epididymis

Pheochromocytoma: Common


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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.


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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


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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




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ATAXIA-TELANGIECTASIA


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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.


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31 mar 16

ATAXIA-TELANGIECTASIA

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,...