NEUROCUTANEOUS SYNDROME

Guide-Dr.Karan Joshi

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

OUTLINE-

• Introduction

• Various Syndromes

• Epidemiology

• Etiology

• Clinical Features

• Diagnosis

• Treatment

INTRODUCTION

Heterogenous group of disorders characterised by the abnormalities of integument and CNS.

Mostly familial.

Defect in differentiation in primitive ectoderm .

The various syndromes include-• Neurofibromatosis

• Tuberous Sclerosis

• Sturge Weber Syndrome

• Von Hippel Lindau Syndrome

• PHACE Syndrome

• Linear nevus Syndrome

• Incontinentia Pigmenti

NEUROFIBROMATOSIS

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

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.

COMMON FEATURES

&

PRESENTATION

CAFE-AU-LAIT SPOTS

• Discrete, well-circumscribed uniformly brown lesions with irregular border

• 5mm(prepubertal)

• 15mm(postpubertal)

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.

LISCH NODULES

A pigmented hamartomatous nevus (a type of benign tumor) affecting the iris.

Neurofibroma and plexiform neurofibroma

Common features of NF2 include:

Hearing loss and tinnitus

Cataracts

Headache

Unsteady gait

Cutaneous neurofibromas

Café-au-lait macules (1%)

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

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

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

TUBEROUS SCLEROSIS(Bourneville’s disease,Epiloia)

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.

PATHOLOGY

Tubers(cerebrum,SER)

Calcification & project into ventrical cavity

(candle dripping appearance)

If present in the foramen of monero

Obstruction of CSF(hydrocephalus)

Clinical Manifestations

Ash-leaf Macule(Reliable early cutaneous sign)

Shagreen Patch

Cafe-au-lait spots Adenoma sebaceous

Subungual fibroma Periungual fibroma

Two astrocytomas

(one is calcified)Renal Angiomyolipoma

The frequency of signs in children with tuberous sclerosis, grouped by age

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

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

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.

Ventriculomegaly and multiple calcified subependymal nodules in the lateral ventricles

Periventricular Tubers

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

STURGE WEBER SYNDROME

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

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%)

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

• 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

Management

• Treat seizure

• Hemispherectomy or lobectomy

• Regular measurements of intraocular pressure with a tenonometer is indicated.

• Flashlamp-pulsed laser therapy

• Special educational facilities

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

• 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

INCONTINENTIA PIGMENTI(Bloch-Sulzberger syndrome)

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.

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.

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%)

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

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

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%)

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

WORKUP AND MANAGEMENT

CT scan & MRI

EEG

No specific treatment

Treat seizures

Multidisciplinary approach

THANKS

Dr.Yashomati Parte