neurocutaneous
TRANSCRIPT
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NEUROCUTANEOUS SYNDROME
Guide-Dr.Karan Joshi
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References:-
• Nelson-Textbook of Pediatrics 19th Edition
• Rudolph-textbook of Pediatrics 21st Edition
• Illustrated synopsis of Dermatology and sexually transmitted diseases- 3rd
Edition….Neena Khanna
• Medscape.com
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OUTLINE-
• Introduction
• Various Syndromes
• Epidemiology
• Etiology
• Clinical Features
• Diagnosis
• Treatment
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INTRODUCTION
Heterogenous group of disorders characterised by the abnormalities of integument and CNS.
Mostly familial.
Defect in differentiation in primitive ectoderm .
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The various syndromes include-• Neurofibromatosis
• Tuberous Sclerosis
• Sturge Weber Syndrome
• Von Hippel Lindau Syndrome
• PHACE Syndrome
• Linear nevus Syndrome
• Incontinentia Pigmenti
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NEUROFIBROMATOSIS
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INTRODUCTION- NF1 and NF2 are autosomal dominant.
50% of cases having no family history.
NF1 is also called Von Recklinghausen disease.
NF2 is also called bilateral acoustic neurofibromatosis
ETIOLOGY
NF1 is caused by DNA mutations located on the long arm of chromosome 17
NF2 is caused by DNA mutations located in the middle of the long arm of chromosome 22
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EPIDEMIOLOGY AND DEMOGRAPHICS
NF 1 is the most common neurocutaneoussyndrome, affecting approximately 1/3000 persons.
NF 2 occurs in about 1/50,000
Equally affects males and females.
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COMMON FEATURES
&
PRESENTATION
CAFE-AU-LAIT SPOTS
• Discrete, well-circumscribed uniformly brown lesions with irregular border
• 5mm(prepubertal)
• 15mm(postpubertal)
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AXILLARY FRECKELS
• Small (0.5cm) brown, well-circumscribed macules.
• Generally go unnoticed.
• High correlation with neurofibromatosis when six or more freckles are present in the axilla.
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LISCH NODULES
A pigmented hamartomatous nevus (a type of benign tumor) affecting the iris.
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Neurofibroma and plexiform neurofibroma
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Common features of NF2 include:
Hearing loss and tinnitus
Cataracts
Headache
Unsteady gait
Cutaneous neurofibromas
Café-au-lait macules (1%)
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DIAGNOSTIC CRITERIANF1 is diagnosed if any 2 of the following 7 are
present:-» Six or more café-au-lait macules >5 mm in prepubertal
patients and >15 mm in postpubertal patients
» Two or more neurofibromas of any type or one plexiform neurofibroma
» Axillary or inguinal freckling
» Optic glioma
» Two or more Lisch nodules
» Sphenoid wing dysplasia or cortical thinning of long bones, with or without pseudarthrosis
» A first-degree relative (parent, sibling, or child) with NF1 based on the previous criteria
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NF 2 diagnosed when any of the following 4 features is present:-
Bilateral eighth nerve masses seen by
appropriate imaging studies-
Bilateral vestibular schwannomas
OR
» A unilateral eighth nerve mass
» A first-degree relative with NF2
» OR two of the following: Neurofibroma, meningioma, glioma, schwannoma or juvenile posterior subcapsular lenticular opacity
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WORKUP AND TREATMENT• Genetic counselling
• Molecular testing
• MRI
MANAGEMENT-
• Supportive &Symptomatic
• Neurologic and educational testing
• Close & disciplinary follow up
• Surgical
All symptomatic cases( visual disturbance,proptosis,
raised ICT) should be assesed without any delay
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TUBEROUS SCLEROSIS(Bourneville’s disease,Epiloia)
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INTRODUCTION
• The classic clinical Triad is Skin lesions in association with Epilepsy and Mental retardation.
• Multisystemic disorder.
ETIOLOGY AND EPIDEMIOLOGY
• Autosomal dominant disorder
• Frequency 1/6,000
• Mutations occur on chromosome 9q34 (TSC1) and 16p13.3 (TSC2). TSC1 gene encode hamartin and TSC2 encodes tuberin
• Half of cases are due to new mutations.
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PATHOLOGY
Tubers(cerebrum,SER)
Calcification & project into ventrical cavity
(candle dripping appearance)
If present in the foramen of monero
Obstruction of CSF(hydrocephalus)
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Clinical Manifestations
Ash-leaf Macule(Reliable early cutaneous sign)
Shagreen Patch
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Cafe-au-lait spots Adenoma sebaceous
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Subungual fibroma Periungual fibroma
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Two astrocytomas
(one is calcified)Renal Angiomyolipoma
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The frequency of signs in children with tuberous sclerosis, grouped by age
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Cortical tuberSubependymal noduleSubependymal giant cell astrocytomaFacial angiofibroma or forehead plaqueUngual or periungual fibromaHypomelanotic macules(>3)Shagreen patchMultiple retinal hamartomasCardiac rhabdomyomaRenal angiomyolipomaPulmonary lymphangiomyomatosis
MAJOR FEATURES OF TUBEROUS SCLEROSIS COMPLEX
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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
MINOR FEATURES OF TUBEROUS SCLEROSIS COMPLEX
TSC is diagnosed when at least 2 major or 1 major plus 2minor features present
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Diagnosis:-• Diagnosis of TS relies on a high index of suspicion when
assessing a child with infantile spasms.
• A careful search for the typical skin and retinal lesions should be completed in all patients with a seizure disorder.
• Head CT scan or MRI confirms the diagnosis in most cases.
• The CT scan typically shows calcified tubers in the periventricular area.
• Molecular testing.
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Ventriculomegaly and multiple calcified subependymal nodules in the lateral ventricles
Periventricular Tubers
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MANAGEMENT:- Control seizures
Infantile spasms associated with TSC, should be given viagabatrin.
Prognosis: 75% of patients with tuberous sclerosis die before the
age of 25 yr, most commonly as a complication of:
– Epilepsy
– Intercurrent infection
– Cardiac failure
– Pulmonary fibrosis
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STURGE WEBER SYNDROME
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INTRODUCTION-
• Occurs sporadically, with a frequency of approximately 1/50,000 and consists of:
• Facial capillary malformation (port-wine stain)
• Leptomeningeal angioma
Patient presents with-
• Seizures
• Hemiparesis
• Transient Stroke
• Headache
• Developmental delay
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Clinical manifestations
• The facial nevus is present at birth,mostly unilateral and always involves the upper face and eyelid.
• Unilateral in 70% and ipsilateral to the venous angioma of the pia
• Even when the facial nevus is bilateral,the pial angioma is usually unilateral
• Buphthalmos and glaucoma of the ipsilateral eye are a common complication
• Seizures
• Hemiparesis
• Mental retardation and learning disabilities(50%)
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Diagnosis
• X-Ray skull- calcification in occipitoparietal region
(mostly) with serpentine or rail track
appearance
• CT head - unilateral cortical atrophy and ipsilateral
dilatation of the lateral ventricle
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• Ophthalmologic evaluation( ROACH SCALE)
Type I: Both facial and leptomeningeal angiomas,
may have glaucoma
Type II: Facial Angioma alone,may have glaucoma
Type III: Isolated leptomeningeal angiomas, no
glaucoma
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Management
• Treat seizure
• Hemispherectomy or lobectomy
• Regular measurements of intraocular pressure with a tenonometer is indicated.
• Flashlamp-pulsed laser therapy
• Special educational facilities
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VON HIPPEL LINDAU DISEASE
• Autosomal dominant
• Affects many organs include cerebellum, spinal cord, medulla, retina, kidney, pancreas, and epididymis.
• Gene mapped in VHL is chromosome 3p25.
• The major neurologic features include
– Cerebellar hemangioblastomas
– Retinal angiomas
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• Patients with cerebellar hemangioblastoma(25%)have retinal angiomas
• Vision is unaffected
• Retinal detachment and visual loss.
MANAGEMENT
• Retinal angiomas should be treated with photocoagulation and cryocoagulation
• Regular follow-up and appropriate imaging studies
Renal carcinoma is the most common cause of death
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INCONTINENTIA PIGMENTI(Bloch-Sulzberger syndrome)
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INTRODUCTION
• X-linked, dominantly inherited disorder of skin pigmentation associated with CNS, ocular, and dental abnormalities.
• Female carriers may have features of stage IV and dental abnormalities
• Lethal in the majority of affected males
• Nuclear factor kappa B essential modulator (NEMO) is located at Xq28.
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Stage 1: ( VESICULAR) • At birth • Linear vesicles, pustules, and bullae with
erythema along the lines of Blaschko.
Stage 2: (VERRUCOUS)• Between ages 2 and 8 weeks • Warty, keratotic papules and plaques.
Stage 3: (HYPERPIGMENTED)• Between ages 12 and 40 weeks.• Macular hyperpigmentation in a swirled pattern
along the lines of Blaschko. Also involve the nipples, axilla, and groin.
Stage 4: (HYPOPIGMENTED)• From infancy through adulthood.• Hypopigmented streaks and/or patches and
cutaneous atrophy.
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CLINICAL FEATURES Skin lesions
Dental anomalies(80%) Late dentitionHypodontiaConical teeth
CNSMotor and cognitive developmental retardationSeizuresMicrocephalySpasticityParalysis(one third).
Ocular anomaliesNeovascularization,MicrophthalmosStrabismus,Optic nerve atrophyCataractsRretrolenticular masses(30%)
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WORKUP AND MANAGEMENT
• CBC
• CT scan & MRI
• Molecular genetics
• Skin biopsy
There is no specific treatment for incontinentia pigmenti.
Stage 1 lesion left intact & keep clean
Dental care
CONSULTATION
o Ophthalmologist
o Dentist
o Neurologist
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PHACE SNDROME• Cutaneous condition characterised by multiple
congenital abnormalities.
• Posterior fossa malformations–hemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternalcleft and supraumbilical raphe syndrome
• Female Predominance
• Unknown underlying pathology
• Large plaque-type facial hemangiomas
• May be associated with Dandy Walker Malformations
• Cerebrovascular & cardiovascular anomalies are common
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LINEAR NEVUS SYNDROME• Characterized by a facial nevus and neurodevelopmental
abnormalities.
• Nevus is located on the forehead and nose
• Midline in its distribution.
PATHLOGY-
Facial nevus includes 3 stages-
1st- Infancy
Alopecia
Hypoplastic sebaceous glands
2nd-Puberty
Hyperplastic sebaceous glands
3rd-Later in life
Tumors(15-20%)
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CLINICAL FEATURES-
• Skin
Facial nevus
• CNS
Seizures
Hemiparesis
Mental retardation
• Occular
Esotropia
Coloboma(iris &choroid)
Homonymous hemianopia
• Others
COA,VSD,Wilms tumor,nephroblastoma,scoliosis,
bony hypertrophy
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WORKUP AND MANAGEMENT
CT scan & MRI
EEG
No specific treatment
Treat seizures
Multidisciplinary approach
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THANKS
Dr.Yashomati Parte