Neurocutaneous Syndromes

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Neurocutaneous Syndromes

• -Dr Jaimin Patel
• (PGY-2)
• -Dr Poorvi Patel
• (pediatric neurologist)

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Definition and Syndromes

• Definition
• Familial/ primitive ectoderm
• All AUTOSOMAL DOMINANT
• List
• Neurofibromatosis I/II
• Tuberous Sclerosis
• Sturge-Weber
• Von Hippel-Lindau
• Ataxia Telengiectesia
• Linear Nevus Syndrome
• Hypomelanosis of Ito
• Incontinentia Pigmenti

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Neurofibromatosis

• Two forms Type I and Type II
• NF-1 Most prevalent
• Incidence 1/4000
• Two out of 7 signs.
• Chromosome 17q11.2

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1-Café au lait macules

• Almost 100, Hallmark
• Trunk and extremities, Spares face
• Measurements.

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2-Axillary or inguinal frekling

• Multiple Hyperpimented areas 2-3 mm in diameter

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3-Iris lish nodules

• Best identified with slit lamp- Hamartomas
  located within the iris.
• gt74 patients with NF-I, two or more
• Prevalence increases with Age- 5lt3 yrs//42 3-4
  yrs // 100 gt21 yrs.

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4a-Neurofibromas

• Two or more -Small, rubbery, purplish skin
• Skin, peripheral nerves, GI tract
• During adolescence and pregnancy.

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4B-Plexiform neurofibroma.

• One
• Hyperpigmented skin
• Overgrowth of extremities/deformity of
  corresponding bone.

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5-distinctive osseous lesions

• Scoliosis is Most Common Orthopedic
  manifestation- Not specific for diagnostic
  criterion
• Cortical thining of long bones with or without
  pseudoarthrosis.

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Which sign is this?
http//bjo.bmj.com/video/collection.dtl
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5-Distinctive osseous lesions

• Sphenoid Dysplasia.

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6-Optic glioma

• Swinging Flash Light test.

http//www.neurology.arizona.edu/Training/c10.html
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• 6-Optic Glioma- Radiologically

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7-Genetics

• First degree Relative with NF-1
• Chromosome 17q11.2

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Complications

• learning disabilities, ADHD, Speech disorder
• Seizures
• Hydrocephalus
• Macrocephaly
• Moya-moya Disease
• Precocious puberty
• Hypertension.
• Fibromuscular dysplasia
• Pheochromocytoma
• Malignancy
• Neurofibrosarcoma
• Malignant Schwanoma

• Abnormal signals in the globus pallidus, thalamus
  and intenal capsule

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Neurofibromatosis II
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Neurofibromatosis II

• Chromosome 22q1.11
• Bilateral acoustic neuromas
• Parent, sibling or child with NF-II
• unilateral eighth nerve mass
• OR
• Neurofibroma, meningioma, glioma, schwannoma or
  juvenile posterior subcapsular lenticular
  opacities.

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Neurofibromatosis II

• Bilateral Acoustic Neuromas
• Hearing loss
• Unsteadiness
• Headache
• Facial weakness
• More commonly in 2nd and 3rd decade.

http//www.med.uc.edu/neurorad/webpage/epa.html
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Neurofibromatosis II

• Subcapsular opacity- 50 of the cases of NF-II

http//www.atlasophthalmology.com/atlasimg/Img0086
_52_low.jpg
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Neurofibromatosis II

• Ependymomas most (80)in spinal cord.
• Spinal Schwannomas (70) intradural
  extramedullary.

http//www.med.uc.edu/neurorad/webpage/epa.html
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Treatment and Management of NF-I and NF-II

• Genetic counseling
• Half result from fresh Mutation
• Prenatal diagnosis in familial cases.

• Tests should be ordered if positive physical
  findings are present
• Annual evaluation
• By pediatrician
• By pediatric ophthalmologist

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Tuberous SclerosisBournevilles Disease
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Tuberous Sclerosis

• 1/6000
• Chromosome 9q34-TSC1-Hamartin
• Chromosome 16p13-TSC2-Tuberin
• Half of the cases are sporadic
• Wide clinical spectrum

• Severe mental retardation
• Seizure disorder

• Normal Intelligence
• No seizures

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Infantile Spasm
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Hypsarrhythmias
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Ash leaf skin lesions

• Hypopigmented in 90 of patients
• Enhanced by woods lamp examination

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Retinal lesions

• Mulberry Tumors
• Retina Nerve fiber and undifferentiated glial
  tissue
• 1/3 to ½ patients
• Can also be found in Neurofibromatosis and Normal
  persons.

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Tuberous Sclerosis

• Sebaceous adenomas Facial Angiofibroma 8-10 and
  then by adolescence fully developed.
• Forehead Plaque.

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Shagreen patch

• Characteristic-Shagreen patch at lower back.

http//www.massgeneral.org/livingwithtsc/affects/s
kin.htm
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Confetti skin lesions
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Characteristic Tubers

• -Candle Dripping appearance.
• -subependymal/decreased neurons/proliferation of
  astrocytes.
• -calcification/obstruction------emedicine

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Cardiac Rhabdomyoma.
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Treatment

• Renal Ultrasound
• Echo
• CT/MRI brain

• Seizure control-ACTH for infantile spasm
• Symptomatic tumor treatment.
• Cosmetic treatments

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Sturge-Weber Disease
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Sturge-Weber Syndrome

• 1/50,000

• Etiology-Anomalous development of the primordial
  vascular bed.

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Port Wine Stainfacial nevus
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Buphthalmos
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Rail-Road Track Calcification

• Gyriform Pattern of the Cortical Calcification.

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Unilateral cortical atrophy
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Treatment

• Seizures-medications to hemispherectomy or
  lobectomy
• Physical Therapy and Rehabilitation
• Ophthalmic evaluations periodically
• Port Wine Stain- Laser.

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Von Hippel-Lindau Disease.
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Von-Hippel-Lindau Disease

• Chromosome 3q25
• Variable penetrance and Delayed expression.
• Cerebellar hemagioblastomas and retinal
  angiomata.
• Affects many organ systems-Cerebellum, spinal
  cord, medulla, retina, kidney, pancreas, and
  epididymis.

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Cerebellar Hemangioblastoma

• Raised Intra Cranial Pressure
• Cystic cerebellar lesion with a vascular mural
  nodule- erythropoietin like protein.
• Spinal Cord-abnormalities of proprioception,
  disturbances of bladder control and gait
  impairement.

http//www.cc.nih.gov/ccc/papers/vonhip/cnshemangi
oblastomas.html
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Retinal Angioma

• Peripheral-Initially vision is unaffected
• Grow, bleed, leave serous fluid-retinal
  detachment
• Small-Laser photocoagulation
• Large-Freezing probe from outside the globe.
• 25 of retinal angioma patients will have
  extraocular manifestation
• 60 with nonocular manifestations will have
  Retinal Angioma.

http//www.kellogg.umich.edu/theeyeshaveit/congeni
tal/retinal-angioma.html
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Von-Hippel-Lindau Disease

• Cystic lesions of
• Kidneys, pancreas, Liver and epididymis
• Pheochromocytomas.
• Renal Carcinoma is Most common cause of death.

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Linear Nevus Syndrome Linear sebaceous nevus
(Jadassohn nevus phacomatosis)
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Linear Sebaceous Nevus
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Linear Nevus Syndrome

• 84-Face
• 50-Scalp, Neck and face
• Scalp lesions devoid of hair

• Seizures in 75
• Infantile spasm
• Generalized Tonic
• Tonic Clonic
• Neurological Deficits
• Cranial Nerve palsies VI, VII
• Cortical Blindness
• Hemiparesis (hemimegalencephaly)
• Mental Retardation-in young children upto70

emedicine
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PHACE Syndrome.

• Posterior fossa malformations
• Hemangiomas
• Arterial anomalies
• Coaractation of the aorta
• Eye abnormalities

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PHACE Syndrome.
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Incontinentia Pigmenti.
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Stage I

• Erythematous linear streaks and plaques of
  vescicles
• DD-Herpes, bullous impetigo, mastocytosis
• eosinophilic spogiosis
• Resolve by 4 mo

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Stage II

• Verrucous plaques
• Dry and hyperkeratotic
• Involute in 6 months

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Stage III

• Hyperpigmentation
• Hallmark
• Macular whorls, linear streaks
• Lines of Blaschko.
• Sites are not necessorily same.
• Invariably affects axilla and groin
• Fade by Early adoleacence.

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Stage IV

• Hypopigmented
• Hairless
• Anhydrotic
• Usually lower legs.

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Other Manifestations

• CNS (33)
• Motor and cognitive developmental retardation
• Seizures
• Microcephaly
• Spasticity
• paralysis

• Dental(80)
• Late dentition
• Hypodontia
• Conical teeth
• Impaction
• Ocular(30)
• Neovascularization
• Microphthalmos
• Strabismus
• Optic Nerve atrophy
• Cataracts
• Retrolenticular masses.

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Genetics

• Functional mosaicism
• Random X-inactivation of an X-linked dominant
  Gene
• Lethal in Males
• Xq28
• Increased Frequency of spontaneous abortions.

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Hypomelanosis of Ito.
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Hypomelanosis of Ito.

• Mosaicism-Family history is rare
• Neurological Association
• Mental retardation (70)
• Seizures (40)
• Microcephaly(25)
• Developmental delay
• Deafness
• Visual problems
• Headache
• Tooth or mouth problems

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Bibliography

• Nelson.
• E-medicine.
• Up-To-Date.
• NIH.
• University of Michigan website
• Massachusetts General hospital website