1. NEUROCUTANEOUS SYNDROMEDR. PANKAJ BAJAJ1ST YEAR DNB PEDIATRICJ.L.N.Hospital & Research Centre, Bhilai Steel Plant5/30/2012 JLNH & RC 1

2. TOPICS TO BECOVERED. DEFINITION CLASSIFICATION DETAILS OF EACH NEUROCUTANEOUS SYNDROME5/30/2012JLNH & RC 2 3. DEFINITION The neurocutaneous syndromes include a Heterogeneous groupof disorders Characterized by abnormalities of both the Integument and central nervous system (CNS). Most disorders are familial and believed to Arise from a defect in differentiation of the Primitive ectoderm.5/30/2012JLNH & RC 3 4. CLASSIFICATION Disorders classified as neurocutaneous syndromesIncludeNeurofibromatosisTuberous SclerosisSturge-Weber SyndromeVon HippelLindau DiseasePHACE SyndromeAtaxia Telangiectasialinear Nevus SyndromeHypomelanosis of ItoNSTLPIncontinentia PigmentiHINT5/30/2012 JLNH & RC 4 5. NEUROFIBROMATOSIS Neurofibromatosis are autosomal dominantDisorders that cause tumors to grow onNerves and result in other abnormalitiessuch As skin changes and bone deformities Neurofibromatosis 1 (NF-1) Neurofibromatosis 2 (NF-2)5/30/2012 JLNH & RC 5 6. NEUROFIBROMATOSIS 1(NF-1) Most prevalent type Incidence of 1/3,000 Autosomal dominant disorder Over half the cases are sporadic,representingDe novo mutations. Chromosome region 17q11.2 Encodes a protein also known asNeurofibromin.5/30/2012 JLNH & RC 6 7. It is diagnosed when any 2 of the following 7 features Arepresent:(1) Six or more Cafe-au-lait macules(2) Axillary or inguinal freckling .(3) Two or more iris Lisch nodules(4) Two or more neurofibromas or 1 plexiform neurofibroma.(5) A distinctive osseous lesion such asSphenoid dysplasia.(6) Optic gliomas low-grade astrocytomas.(7) A first-degree relative with NF-1.5/30/2012 JLNH & RC 7 8. Cafe-au-lait macules Over 5 mm in greatest diameter in prepubertal individuals. Over 15 mm in greatest diameter in postpubertal individuals. Hallmark of neurofibromatosis almost 100% of patients. Present at birth but increase in size, number, and pigmentation, especially duringThe first few yrs of life. 5/30/2012JLNH & RC8 Predilection for the trunk and extremities but sparing the face. 9. Axillary or inguinal freckling Multiple hyperpigmented areas 2-3 mm in diameter. Skinfold freckling usually appears between 3 and 5 yr of age. Frequency greater than 80% by 6 yr of age. 5/30/2012JLNH & RC 9 10. Two or more iris Lisch nodules Hamartomas. located within the iris . Best identified by a slit-lamp examination. They are present in >74% of patients with NF-1 but are not a component of NF-2. The prevalence increases with age. Only 5% of children 3) Shagreen patch Multiple retinal hamartomas Cardiac rhabdomyoma Renal angiomyolipoma Pulmonary lymphangioleiomyomatosis5/30/2012 JLNH & RC27 28. MINOR FEATURES OF TUBEROUSSCLEROSIS COMPLEXCerebral white matter migration lines Multiple dental pits Gingival fibromas Bone cysts Retinal achromatic patch Confetti skin lesions Nonrenal hamartomas Multiple renal cysts Hamartomatous rectal polyps5/30/2012JLNH & RC 28 29. Ash leaf skin lesions at least 3 hypomelanotic macules must bepresent Hypopigmented in 90% of patients Enhanced by woods lamp examination At least 3 hypomelanotic macules must5/30/2012JLNH & RCbe present29 30. Retinal lesions Mulberry Tumors Retina Nerve fiber and undifferentiated glial tissue 1/3 to patients Can also be found in Neurofibromatosis and Normal persons.5/30/2012JLNH & RC 30 31. Tuberous Sclerosis Sebaceous adenomas Facial Angiofibroma 8-10 . by adolescence fully developed Forehead Plaque.5/30/2012 JLNH & RC 31 32. Shagreen patch Roughened, raised lesion with an Orange-peelconsistencylocated Primarily in the lumbosacral region5/30/2012 JLNH & RChttp://www.massgeneral.org/livingwithtsc/affects/skin.htm 32 33. Ungual or periungual fibroma5/30/2012 JLNH & RC 33 34. Confetti skin lesions5/30/2012 JLNH & RC34 35. Characteristic Tubers -Candle Dripping appearance. -subependymal/decreased neurons/proliferation of astrocytes. 5/30/2012 -calcification/obstruction------emedicineJLNH & RC 35 36. Cardiac Rhabdomyoma.5/30/2012 JLNH & RC 36 37. Infantile SpasmHypsarrhythmias5/30/2012JLNH & RC 37 38. Treatment Renal Ultrasound Seizure control- Echo ACTH for infantile CT/MRI brain spasm Symptomatic tumor treatment. Cosmetic treatments For treatment of SEGAs- everolimus 5/30/2012 JLNH & RC subependymal giant cell astrocytomas 38 39. kidneys angiomyolipomas The current recommendation is to followThem by yearly imaging, and when thelesion Becomes larger than 4 cm, to useTranscatheter Tumor embolization fortreatment5/30/2012 JLNH & RC 39 40. ROUTINE FOLLOW-UPPhysical examination: Brain MRI every 1-3 yr, Renal imaging (ultrasound, CT, or MRI)every 1-3 yr Neurodevelopmental testing at the time ofBeginning 1st grade.5/30/2012JLNH & RC40 41. Sturge-Weber Syndrome Sturge-Weber syndrome (SWS) is asporadic Vascular disorder and consists of aConstellation of symptoms and signsincluding A facial capillary malformation(port-wine Stain), abnormal blood vesselsof the brain (leptomeningeal angioma), andabnormal Blood vessels of the eye leadingto glaucoma.5/30/2012 JLNH & RC 41 42. 1 per 50,000 live births have SWS. Etiology remains unclear. ??Anomalousdevelopment oftheembryonic vascular bed in the early stagesof facial and cerebral development.5/30/2012JLNH & RC42 43. Clinical Manifestations The facial port-wine stain. Overall incidence be 8-33% The capillary malformation. Buphthalmos and glaucoma Transient strokelike episodes or visualdefects Result From thrombosis of corticalveins. Mental retardation or severe learning5/30/2012JLNH & RC 43Disabilities 50% In later childhood. 44. Unilateral, and always involves the upper face And eyelid, in a distribution consistent with the Ophthalmic division of the trigeminal nerve. Port Wine Stain5/30/2012 facial nevusJLNH & RC 44 45. Buphthalmos5/30/2012JLNH & RC 45 46. Epilepsy75-90%,1st yr of life.Focal tonic-clonic and Contralateral to theside Of the facial capillary Malformation.Refractory to anticonvulsants associatedWith A slowly progressive hemiparesis .5/30/2012JLNH & RC 46 47. Diagnosis Based on the involvement of the brain and theFace, there are 3 types according to the RoachScale: 1 Type I: Both facial and leptomeningealAngiomas; may have glaucoma2 Type II: Facial angioma alone (no CNSInvolvement); may have glaucoma3 Type III: Isolated leptomeningealangiomas; Usually no glaucoma5/30/2012JLNH & RC 47 48. Rail-Road Track Calcification Gyriform Pattern of the Cortical5/30/2012JLNH & RCCalcification. 48 49. Unilateral cortical atrophy5/30/2012 JLNH & RC 49 50. Treatment Symptomatic and multidisciplinary. It is aimed at Controlling seizures Treating headaches Preventing strokelike episodes Monitoring for Glaucoma5/30/2012JLNH & RC 50 51. laser therapy for the cutaneous capillaryMalformations. Ifthe seizures are refractory toanticonvulsant therapy Than considerhemispherectomy. Regular measurement of intraocularpressure. Pulsed dye laser therapy for port-winestain, ParticularlyJLNH & RC is located on the5/30/2012if it 51 52. Von HippelLindau Disease Von HippelLindau (VHL) disease affectsmany Organs, including thecerebellum, spinalcord, Retina, kidney, pancreas, andepididymis. Incidence is around 1:36,000. Autosomal dominant mutation affecting aTumor suppressor gene, VHL. Chromosome 3q25. & RC5/30/2012JLNH 52 53. Include cerebellar hemangioblastomas andRetinal angiomas. Cystic lesions of thekidneys, pancreas, liver, And epididymis aswell as pheochromocytoma Are frequentlyassociated. Renal carcinoma is the most common causeof Death.5/30/2012 JLNH & RC 53 54. Cerebellar Hemangioblastoma Raised Intra CranialPressure Cystic cerebellar lesionwith a vascular muralnodule- erythropoietinlike protein. Spinal Cord-abnormalities ofproprioception, disturbances of bladder controland gait impairement.http://www.cc.nih.gov/ccc/papers/vonhip/cnshemangioblastomas.html5/30/2012 JLNH & RC 54 55. Retinal Angioma Peripheral-Initially vision isunaffected Grow, bleed, leave serousfluid-retinal detachment Small-Laser photocoagulation Large-Freezing probe fromoutside the globe. 25% of retinal angiomapatients will have extraocularmanifestation 60% with nonocularmanifestations will haveRetinal Angioma.http://www.kellogg.umich.edu/theeyeshaveit/congenital/retinal-angioma.html5/30/2012JLNH & RC 56. PHACE/S SyndromePosterior fossa malformationsHemangiomasArterial anomaliesCoaractation of the aortaEye abnormalities+Sternal clefting and/or a supraumbilical raphe5/30/2012 JLNH & RC56 57. Ataxia Telangiectasia Ataxia telangiectasia (A-T) is a ProgressiveDegenerative disease involving many majorbody Systems. It is an autosomal recessive disease. A-T is usually noticed in the second year oflife as a Child develops problems with balanceand Slurred Speech caused by ataxia (lack ofmuscle control). The ataxia occurs because the cerebellum, thepart of The brain that controls musclemovement, is Degenerating.5/30/2012JLNH & RC57 58. Characterisedby telangiectasia of Conjunctiva,nose, ears and skin creases.About 70% of children with A-T also have Immune system problems that make Them more susceptible to chronic URTI, lung infections, and certain cancers, such As leukaemia5/30/2012 JLNH & RC58 59. Currently, there is no cure for A-T and noway To stop its progression. But treatmentcan help Kids manage symptoms. Physical therapy and occupational therapymay Help maintain flexibility. Speech therapy can help address slurringand Other speech problems.5/30/2012JLNH & RC59 60. linear Nevus Syndrome This sporadic condition is characterized bya Facial nevus and neurodevelopmentalAbnormalities. The nevus is located on the forehead andnose And tends to be midline in itsdistribution.5/30/2012 JLNH & RC60 61. 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%5/30/2012 JLNH & RC61 62. Hypomelanosis of Ito.5/30/2012 JLNH & RC62 63. Mosaicism-Family history is rare Neurological Association Mental retardation (70%) Seizures (40%) Microcephaly(25%) Developmental delay Deafness Visual problems Headache Tooth or mouth problems5/30/2012JLNH & RC 63 64. Incontinentia Pigmenti This heritable, multisystem ectodermaldisorder features dermatologic, dental, andocular abnormalities Functional mosaicism Random X-inactivation of an X-linkeddominant Gene (IKK-gamma/NEMO gene) Lethal in Males Xq28 Increased Frequency of spontaneous abortions.5/30/2012 JLNH & RC64 65. Stage I Erythematous linear streaks and plaques of vescicles DD-Herpes, bullous impetigo, mastocytos is eosinophilic spogiosis5/30/2012 Resolve by 4 mo JLNH & RC 65 66. Stage II Verrucous plaques Dry andhyperkeratotic Involute in 6 months5/30/2012 JLNH & RC66 67. Stage III Hyperpigmentation Hallmark Macular whorls, linearstreaks Lines of Blaschko. Sites are not necessorilysame. Invariably affects axillaand groin Fade by Earlyadoleacence.5/30/2012 JLNH & RC 67 68. Stage IV Hypopigmented Hairless Anhydrotic Usually lower legs.5/30/2012 JLNH & RC68 69. Other ManifestationsCNS (33%) Dental(80%) Late dentition Motor and cognitive Hypodontia developmental Conical teeth retardation Impaction Seizures Ocular(30%) Neovascularization Microcephaly Microphthalmos Spasticity Strabismus Optic Nerve atrophy paralysis Cataracts Retrolenticular masses.5/30/2012JLNH & RC 69 70. THANK YOU5/30/2012JLNH & RC 70