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NEUROCUTANEOUS DISORDERS AND SYNDROMES

NEUROCUTANEOUS DISORDERS AND SYNDROMES. Bořivoj Petrák Klinika dětské neurologie, 2.LF UK a FN Motol 2019. NEUROCUTANEOUS DISORDERS AND SYNDROMES 1). The earlier term ( historical name ) „ phacomatosis “

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NEUROCUTANEOUS DISORDERS AND SYNDROMES

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  1. NEUROCUTANEOUS DISORDERS AND SYNDROMES Bořivoj Petrák Klinika dětské neurologie, 2.LF UK a FN Motol 2019

  2. NEUROCUTANEOUS DISORDERS AND SYNDROMES 1) • Theearlier term (historicalname) „phacomatosis“ • Neurocutaneousdiseases/syndromes (currentname) are congenitalandhereditaryconditionswithlesionsbothoftheskinandthenervoussystemandtheother body organs(bone, eye, kidney, heart, lungs, vessels) - derivedfromneuroectoderm– neural tube andcrest. • They are complexmultisystemdisorderswithveryvariableclinicalfeatures. • Theyinclude a largegroupofneurologicaldisordersthat feature cutaneousandeyelesions, centralandperipheralnervoussystemtumors, brainmalformations, mentalretardation, psychiatric syndrome andseizures. • These units are slowlyprogressing.

  3. NEUROCUTANEOUS DISORDERS AND SYNDROMES 2)Commonsigns • 1) Inheritance • The majority displayingMendelian inheritance = single gene conditions, andthecommonneurocutaneous syndrome are autosomal dominant (AD) inherited, withfull penetrance (to someage), largeexpressivityandvariability (= widespectrumofdiseasephenotypesvaryingfrommild to severe forms), andwith much highercasesofnewmutations (= sporadiccases). • Otherneurocutaneoussyndromes (rareunits) are autosomalrecessively (AR) and X-linked (XD, XR) inherited, someoccur as a resultofmosaicismformutations in dominantlyinheritedlethalgenes.

  4. NEUROCUTANEOUS DISORDERS AND SYNDROMES 3)Commonsigns • Exampleofthe inheritance: • Autosomal dominant (AD) inherited: neurofibromatosisvonRecklinghausen type 1, tuberoussclerosis, withlargenumbersporadiccases. • Autosomalrecessively (AR) inherited: ataxia – telangiectasia • X-linked dominant disorder (XD): incontinentiapigmenti • X-linkedrecessivedisorder (XR): kinkyhair syndrome (Menkes syndrome) • mosaicismformutations in dominantlyinheritedlethalgenes: Proteus sy, Epidermalnevussy

  5. NEUROCUTANEOUS DISORDERS AND SYNDROMES 4)Commonsigns • 2) They are congenitalconditionsderivedfromgerminalneuroectodermwithlesionsoftheboththe skin andthenervoussystem (neural tube), and bone, eye, kidney, heart, lungs, vessels (neuralcrest). • Theseunits are germ cell migration disorders. .

  6. NEUROCUTANEOUS DISORDERS AND SYNDROMES 5)Commonsigns • After recruitment from the ectoderm, the neuroectoderm undergoes three stages of development: transformation into the neural plate, transformation into the neural groove (with associated neural folds), and transformation into the neural tube. After formation of the tube, the brain forms into three sections; the hindbrain, the midbrain, and the forebrain. • The types of neuroectoderm include: • Neural crest: -pigment cells in the skin, - ganglia of the autonomic nervous systém, - dorsal root ganglia, - facial cartilage, - aorticopulmonary septum of the developing heart and lungs, - ciliary body of the eye, - adrenal medulla, - parafollicular cells in the thyroid • Neural tube: - brain (rhombencephalon, mesencephalon and prosencephalon) • spinal cord and motor neurons • retina • posterior pituitary

  7. NEUROCUTANEOUS DISORDERS AND SYNDROMES 6)Commonsigns • 3) Many are associatedwithhigh risk fortumors (oncogenesis). - Howeverneurocutaneoussyndromes are mainlyhamartomatosissyndromes - there are commonofthebenigntumorsthere - only a fewofhavemalignanttumors. Predisposition = tumor suppressorgenes = hypothesisofthetwo-hit mechanism (hypothesis by Knudson, 1972) Somebenigntumorscanbedestructiveand „malignant“ by position

  8. NEUROCUTANEOUS DISORDERS AND SYNDROMES 7)Commondiseasesandsyndromes • NeurofibromatosisvonRecklinghausen • type 1 (NF1) 17q11.2, AD, 1: 3000-4000 • type 2 (NF2) 22q12.2, AD, 1: 30 000-40 000 – itoccuratadult • Schwanomatosis 22q, AD, 1:40 000, itoccuratadult • Tuberoussclerosiscomplex (M. Bourneville-Pringle, TSC), AD, 1: 7000 - 10 000 (USA) • typ 1 (TSC1) 9q34 • typ 2 (TSC2) 16p13.3 • Sturge-Weber syndrom,(SWS) sporadiccases, 1:50 000 • M. vonHippel-Lindau,(VHL) 3p26-p25, AD, 1:36000– 53000 – onlyadult • Ataxia-telangiectasia (AT) 11q22.3, AR, 1:40000-100 000 Theotherapproximately 40 units are rareorveryrare.

  9. NEUROCUTANEOUS DISORDERS AND SYNDROMES 8)Recommendedresources • NeurocutaneousDisorders. Ed. Roach ES and Miller VS. Cambridge Univ. Press, 2004, UK. • Child Neurology. Ed. Menkes JH, Sarnat HB, Maria BM, seventhedition, Chapter 12th, Neurocutaneoussyndromes., 2009, LippincottWilliamsandWilkins.

  10. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1)

  11. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 1) • The most commonneurocutaneous syndrome • NF1 is a distinctdisorderandis not related to neurofibromatosis type 2 (NF2) • Multisystemdisorder • Affecting1 in 3000-4000 individualsworldwidewithoutregardforethnicorracial background • NF1 isADinherited, withfull penetrance (to adultage), largeexpressivityandvariability (= widespectrumofdiseasephenotypesvaryingfrommild to severe forms), • 30-50%newmutation = sporadiccases

  12. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 2) • The NF1 gene wasidentifedat 1987 • Islocated on thelongarmof chromosome 17q11.2nearthecentromere • 60exons, 335kilobasesofgenomic DNA (kbDNA) • The NF1 gene productistermedneurofibromin, 13 kbmRNA, 2818 AMK • Tumor-suppressor gene, LOH • ExistDNA analysis

  13. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 3) • Neurofibromin: • Neurofibrominis a GTPase-activating protein (GAP), whichfunctions to inhibit ras activity (activationof ras promotes cell divisionandproliferation). • Neurofibromin, as a negative regulatorof ras, mayfunction as a tumor suppressorby inhibitingthe ras-mediated cell proliferationsignal. • Lossofneurofibromin= increasing ras activityand cell proliferation, anditthatfashionpromote tumor formation.

  14. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 4) • NF1 andtumors: • Hamartomas • Benigntumors:- peripheralnervoussystem: - neurofibromas (NF) = are composedofSchwanncellsandfibroblasts + maycontainperineuralcells, mast cells NF maybeclassifiedinto: a) cutaneous NF, b) subcutaneous NF, c) deepnodular NF, d) plexiformneurofibroma (plex.NF)

  15. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 5) • Centralnervoussystem– opticpathwaygliomas(grade I pilocytisastrocytoma) are in the15-20%of NF1 individuals, andlow grade gliomain theotherlocalisation (pons, basal ganglia) ofthebrainand/orless in the spinal cord. • Opticpathwayglioma (OPG) maybefoundatanylocationalongtheopticpathway – most commonlyatopticchiasmandatoptic nerve (includingbilateralaffection). • Theageofpresentationisusuallyunder6 (10) years. • - from½ to 2/3OPG are asymptomatic = withanyhealthproblem. • SymptomaticOPGwithproptosis, opticdysfunction, decresevisualacuity, color vision changes, visualloss, strabismus, optic nerve atrophy, papilledema.

  16. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 6) Only a smallfractionof NF1-associatedsymptomaticOPG requiretreatment. Remember!! The OPG withtheexclusionof NF1 (NF1-unassociated) are seriousoncologicdiseaseandrequiretreatmentalways. • Treatmentof NF1-associatedsymptomatic OPGhas recentlyincludedchemoterapy – withcarboplatinumandvincristine. • Radiationwas standard treatment to 2000, itwasleaveforgreat risk ofcognitive, endocrineandvascullarchanges (moya-moyasy). • Surgicaltreatmentoftheintraorbital/prechiasmatic OPG wasleaveforgreat risk ofthevisualloss, ptosis.

  17. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 7) Malignancies in NF1 Peripheralnervoussystem: • Malignantperipheral nerve sheat tumor (MPNST) – derivedfromSchwanncells (de novo) orfromplexiform NF aftermalignanttransformation. • Risk of MPNST iswith a rateof 2-10% Othermalignancies: • Pheochromocytoma • Hemoblastoses • Wilm´s tumor • Rhabdomyosarcoma • GIST (gastrointestinalstromal tumor) • Neuroblastoma

  18. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 8) Diagnosticcriteria NF1 • Atleasttwoclinicalfeaturesfromthe list ofthediagnosticcriteriamustbepresent in order to establishdiagnosisof NF1. Diagnosticcriteria: • Sixor more café- au- laitmacules, greaterthan 5 mm in diameter in a prepubertalpatientand 1.5 cm in a postpubertalpatients. • Axillaryorinquinalyfreckling • Twoor more NF and/oroneor more plexiform NF. • OPG • Twoor more Lischnodules • Characteristic bony lesion • First-degreerelativewith NF1

  19. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 9) Otherclinicalmanifestation NF1 • Hypersignalareas on T2-weightedimages = = Focalareasofsignal intensity (FASI) • Skoliosisandskeletal abnormality andchanges • Hydrocephalus – glioma x aqueductalstenosis • Other: macrocephaly, short statue, learningdisabilities, ADD and ADHD, endocrinopathy. • Rarefindings: fibromusculardysplasy, stroke (incl. moya-moya syndrome), hypertension (renovasculary), epilepsy (7%).

  20. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 10) Otherclinicalmanifestation NF1 • Hypersignalareas on T2-weightedimages = Focalareasofsignal intensity (FASI) • Synonyms = Commonlythey are referred as unidentifiedbrightobject (UBO) orhamartoma • Theyhavebeenidentified inthecerebellum, brain stem, thalamus, andbasal ganglia, especially in 86% childrenandadolescents. • Histologicalanalysis – vacuolarorspongioticalterationofthe myeline in thewhitematter • Itisnot a tumor – theoretical risk ofthelow-grade glioma - itdistinguished by the absence ofmass-effectand/orenhancement by contrastmatter

  21. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 11) Otherclinicalmanifestation NF1 • Skoliosisandskeletal abnormality andchanges– from 10 yearsofage, 2% in orthopedicsurgery • FASI • Hydrocephalus – glioma x aqueductalstenosis • Other: macrocephaly, short statue, learningdisabilities, ADD and ADHD, endocrinopathy. • Rarefindings: fibromusculardysplasy, stroke (incl. moya-moya syndrome), hypertension (renovasculary), epilepsy (7%).

  22. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 12) Otherclinicalmanifestation NF1 • Hydrocephalus – glioma x aqueductalstenosis (in cohortofthechildrenwith NF1 in Paediatric Neurology Dpt. Motol) Thedevelopmentofobstructivehydrocephalus 25/275 = 9% Thedevelopmentdue to aqueductalstenosis7/275 (2.5%), resp. 7/25(28%) • FASI • Skoliosisandskeletal abnormality andchanges • Other: macrocephaly, short statue, learningdisabilities, ADD and ADHD, endocrinopathy. • Rarefindings: fibromusculardysplasy, stroke (incl. moya-moya syndrome), hypertension (renovasculary), epilepsy (7%).

  23. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 13) Otherclinicalmanifestation NF1 • Other: macrocephaly, short statue, learningdisabilities, ADD and ADHD, endocrinopathy. • FASI • Skoliosisandskeletal abnormality andchanges • Hydrocephalus – glioma x aqueductalstenosis • Rarefindings: fibromusculardysplasy, stroke (incl. moya-moya syndrome), hypertension (renovasculary), epilepsy (7%).

  24. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 1 (NF1) 14) Otherclinicalmanifestation NF1 • Rarefindings: fibromusculardysplasy, stroke (incl. moya-moya syndrome), hypertension (renovasculary), epilepsy (7%). • Hypersignalareas on T2-weightedimages = Foci of altered signal intensity (FASI) = Focalareasofsignal intensity (FASI) • Skoliosisandskeletal abnormality andchanges • Hydrocephalus – glioma x aqueductalstenosis • Other: macrocephaly, short statue, learningdisabilities, ADD and ADHD, endocrinopathy.

  25. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYPE 2 (NF2)

  26. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYPE 2 (NF2) 1) • NF2is a distinctdisorderandis not related to NF1 • NF2 predisposesaffectedindividuals to thedevelopmentofbillateralvestibularschwannomas • Multi-(benign)tumor disease (everyone= twoor more) • Affecting1 in 30000-40000 individualsworldwide • NF2 isADinherited, withonset in adolescent andyoungadultage. • 50%newmutation = sporadiccases • The NF2 gene wasidentifedat 1987. Islocated on thelongarmof chromosome 22q12.2, contains17exons. TheNF2 gene productistermedschwannomin(=merlin) • Tumor-suppressor gene, LOH

  27. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 2 (NF2) 2) • ExistpossibilityofDNA analysis • The majority ofindividualswithNF2 presentwith hearingloss– accompanied/preceded by tinnitus, anddizzinessorimbalance as thefirst symptom • A significantnumberofpatientspresentinitiallywithcranialmeningioma, spinal tumor orcutaneous tumor (20-30%). • Between 60 and 80% ofpatientswith NF2 have evidence ofcataract – presenileposteriorsubcapsularlenticularopacities

  28. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 2 (NF2) 3) Diagnosticcriteriafor NF2 Bilateralvestibularschwannomasorfamilyhistoryof NF2 + • Unilateralvestibularschwannomaor • Anytwoof : meningioma, glioma, neurofibroma, schwannoma, andpresenileposteriorsubcapsularlenticularopacities • Additionalcriteria - Cerebralcalcification

  29. NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYP 2 (NF2) 4) Management issues • Theonsetsymptoms= only 10% ofcases are symptomaticbefore 10 yearsofage • Screeningforvestibularschwannomasshouldbeginaround 10-12 yearsofage – audiologicaltesting, brainstem auditory evokedpotential (BAEP) • MRI scansare theimagingtechniqueofchoice= detectsmallertumors (+contrast) than CT andavoidthe risk ofradiation • Therapy – surgical management – otolaryngology, neurosurgery + newtechniques: brainstemimplants - clinicalgenetic= prenataldiagnosis, preimplantationdiagnosis

  30. TUBEROUS SCLEROSIS COMPLEX (TSC) M.BOURNEVILLE - PRINGLE

  31. TUBEROUS SKLEROSIS COMPLEX 1) • Thesecond most commondiseaseoftheneurocutaneous syndrome group • Multisystemdisorder (brain, skin, heart, kidneys, liver, lung, bone). • Population-basedstudiessuggest a prevalence of1 in 6000-9000 individualsworldwidewithoutregardforethnicorracial background • TSC isADinherited, withlargeexpressivityandvariability (= widespectrumofdiseasephenotypesvaryingfromsubtlefindings to severe forms), and60%- 80%resultfromsporadiccases. • Germlinemosaicismaccountsfor1% or 2% • Twogenes are responsiblefor TSC • TSC type 1 - chromozome 9q34.3, hamartin • TSC type 2 - chromozome 16p13.3, tuberin • hamartin-tuberincomplex – twogenes cause similarphenotypesbecausetheyinteract in thesameprocess = mTORkinasepathway (mammalianTargetofRapamycin) – phosphorylationandgrowth/proliferationofthecells

  32. TUBEROUS SKLEROSIS COMPLEX 2) Diagnosticcriteria TSC – the last upgrade at 2012 Part A)Geneticdiagnosticcriteria Part B)Clinicaldiagnosticcriteria Twogroupsofthediagnosticfeaturesexist: – major features(11) - minorfeatures(6) • Definite TSC diagnosis: • Genetic: Theidentificationofeither a TSC1 or TSC2 pathogenicmutation in DNA fromnormaltissueissufficient to make a definediagnosisof TSC. • Clinical: • Eithertwomajorfeaturesorone major feature + twominorfeatures. • Probable TSC diagnosis: One major feature + oneminorfeature • Suspect TSC diagnosis: One major feature ortwoor more minorfeatures. (Northrup H etal., 2013)

  33. TUBEROUS SKLEROSIS COMPLEX 3) Part A) Geneticdiagnosticcriteria Theidentificationofeither a TSC1 or TSC2 pathogenicmutation in DNA fromnormaltissueissufficient to make a definediagnosisof TSC. A pathogenicmutationisdefined as a mutationthatclearlyinactivatesthefunctionofthe TSC1 or TSC2 proteins (eg, outofframeindelor nonsense mutation), prevents protein synthesis (eg, largegenomicdeletion), oris a missencemutationwhoseeffect on protein function has beenestablished by functionalassessment (www.lovd.nl/TSC1, www.lovd.nl/TSC2). Other TSC1 or TSC2 variantswhoseeffect on functionislesscertain do not meet these criteriaand are not sufficient to make a definitediagnosisof TSC. Notethat 10% to 25% of TSC patientshave no mutationidentified by conventionalgenetictesting, andnormalresultdoes not exclude TSC, orhaveanyeffect on the use ofClinicalDiagnosticCriterïa to diagnose TSC. (Northrup H etal., 2013)

  34. TUBEROUS SKLEROSIS COMPLEX 4) Part B: Clinicaldiagnosticcriteria Major features (11) • Hypomelanoticmacules (3 or more, atleast 5-mm diameter) • Angiofibromas (3 or more) orfibrouscephalicplaque • Ungualfibromas (2 or more) • Shagreenpatch(1-4 skin) • Multiple retinalhamartomas • Corticaldysplasias(includestubers+cerebralwhitematterradialmigrationlines) • Subependymalnodule(SEN) • Subependymalgiant cell astrocytoma(SEGA) (6-8 brain) • Cardiacrhabdomyoma(CR) • Lymphangioleiomyomatosis (LAM) (A combinationofthe 2 major clinicalfeatures LAM andangiomyolipomaswithoutotherfeaturesdoes not meetcriteriafor a definitediagnosis). • Angiomyolipomas (2 or more) (9-11 organs) (Northrup H etal., 2013)

  35. TUBEROUS SKLEROSIS COMPLEX 5) Minorfeatures (6) • „Confetti“ skin lesion • Dentalenamelpits (more than 3) • Intraoralfibromas (2 or more) • Retinalachromicpatch • Multiple renalcysts • Non-renalhamartomas (Northrup H etal, 2013)

  36. TUBEROUS SKLEROSIS COMPLEX 6) Clinicalmanifestation – skin lesions1/ • Hypomelanoticmacules: • are found in over 90% ofpatients = threeor more • oneortwoof these lesionsoccur in normalindividuals • theycanbefound in thenewborn, theprogressionlater • theyoccurlessoften in thescalphairoreyelids = poliosis • these hamartomasshinesbrightly in ultraviolet light • Facialangiofibromas: • are foundin about 75% ofpatients • containbothvascularandconnectivetissueelements • becomeapparentduringthepreschoolyears, progressionlater • Therapy – surgical management – otolaryngology, neurosurgery + newtechniques: brainstemimplants - clinicalgenetic= prenataldiagnosis, preimplantationdiagnosis

  37. TUBEROUS SKLEROSIS COMPLEX 7) Clinicalmanifestation – skin lesions2/ 3. Shagreenpatch: • textured skin lesion are found in about 30% ofpatients • they are most oftenfound on thebackor flank area • histologicallytheyhavecharacterofepidermalnaevus • becomeapparentduringthepreschool/schoolyears 4.Ungualfibromas: • nodularfleshytumorsarisingadjacent to, orunderneath, thenails. Single lesionssometimesdevelopafter trauma. • containbothvascularandconnectivetissueelements • are found in about 15-20% of TSC patients - occurred in adolescentsoradult

  38. TUBEROUS SKLEROSIS COMPLEX 8) Clinicalmanifestation – brainlesions1/ • Cortical tuber: • are found in over 100% of TSC patients • theycanbefound in thenewborn, the „progression“laterwithmyelinization • theyoccur • these dysplasticareas • Subependymalnodule (SEN) • are foundin about 100% of TSC patients • containcalcification • Minimallifetimegrowth

  39. TUBEROUS SKLEROSIS COMPLEX 9) Clinicalmanifestation – brainlesions2/ 3.Subependymalgiant cell astrocytoma (SEGA): • are found in over 12-16% of TSC patients • theycanbefound in thenewbornonlyrarely, the „progression“later • theycan to occurobstructionoftheforaminaMonroeanddevelopmentofhydrocephalus

  40. TUBEROUS SKLEROSIS COMPLEX 10) Clinicalmanifestation – neurologicdysfunction Thepredominantneurologicmanifestationsof TSC are mentalretardation, epilepticseizures, andbehavioralabnormalities. Butindividualswithlittleor no neurologicimpairmentexist. Mentalretardation (40-60%) – intellectualfunctionrangesfromaboveaverage to profoundmentalretardation. Epilepticseizures • are foundin about 90% ofpatients • ofvarioustypes, includinginfantilespasms (Westsy) • therapy– vigabatrine (Sabriltbl) and/orcombinationoftheantiepilepticdrugs. • epilepticsurgeryispossible.

  41. TUBEROUS SKLEROSIS COMPLEX 11) Management issues1/ • Theonsetsymptoms= thefirstclinical feature TSC iscardiacrhabdomyoma (CR). CR(s) are sometimesseen on prenatalultrasound- itisnecessarylongtimefollow-up = earlydiagnosis TSC, andcomplications, particularlydevelopmentofepilepsy. • Periodicevaluationto detectthe more seriouscomplications (CR, cardiacarrhythmias, epilepsy), mentalretardation,behavioraldisorders (autism, hyperkinesis, ADHD sy), tumors (SEGA, renaltumors, LAM). • MRI istheimagingtechniqueofchoice= detectcorticalandcortico-subcorticallesions (tuber), and SEGA (+contrastenhancement). Calcifiedsubependymalnodules are bestdemonstratedwith CT.

  42. TUBEROUS SKLEROSIS COMPLEX 12) Management issues2/ 4.Therapy - epilepsy – antiepilepticdrugs (AED) includingvigabatrin (Sabriltbl), combination – surgical management – LAM, renal cyst andangiolipoma - neurosurgery - hydrocephalus, epileptosurgery, andbraintumors/SEGA - clinicalgenetic= evaluationincludingmolecularexamination/DNA analysis, prenataldiagnosis, preimplantationdiagnosis

  43. STURGE – WEBER syndrome (SWS) (encephalofacialangiomatosis)

  44. Sturge – Weber syndrome(SWS) 1) • SWS is a rareneurocutaneousdisorder. • Population-basedstudiessuggest a prevalence of1 in 50 000 individualsworldwidewithoutregardforethnicorracial background • SWSisinherited, butonlysporadic case/ newmutation. • Hypothesis = mosaicismofthelethal gene. • Tumor risk – pheochromocytoma, angioma (organs)

  45. Sturge – Weber syndrome(SWS) 2) • SWS is associated with – diagnosticcriteria: • unilateralorbilateralport-winestain(s)of the face =area ofthe1th (and 2nd) nervus trigeminus branche(s) + butonly 8% to 20% ofindividualswiththis port-winestaindevelop SWS andneurologicaldysfunction 2) ipsilateralleptomeningealangioma= malformation of blood vessels in thepia mater + gyralcalcification(classic feature = „trolley track“) on CT examinationofthehead + extensivecerebralatrophy + MRI examinationwith gadolinium contrast(!) isnecessary 3)glaucoma, occurs in 71%ofthepatients, episcleralhemangioma, developmentpeaksattwoages, + buphthalmos (bornwithanenlarged globe)

  46. Sturge – Weber syndrome(SWS) 3) • SWSisoftenassociatedwith: • seizures (simplepartialseizuresand sec.generalization) + epilepsyoccurs in up to 80%ofSWS patients + epilepsyoccurs in up to 93%withbil.braininvolvement + otherseizuretypes= infantilespasms, tonic-clonicseizures, myoclonicandgelasticseizures • hemiparesis + arrestedgrowth in theweakextremities • hemianopia • mentalretardationand/ordevelopmentaldelay(lessthan 10% of SWS patientswithbilateralinvolvement are intelectuallynormal) • cognitivedysfunction(frequently) andattention deficit hyperactivitydisorder (ADHD sy). • headache, migraineand/orstroke-likeepisodes

  47. Sturge – Weber syndrome(SWS) 4) Therapy: • Epilepsy= anticonvulsants (AED) - completeseizurecontrolispossibleonly in somepatients = improvethequalityoflife • patientswithunilateralbrainlesionswhofail to respond to medication (catastrophicepilepsy) maybenefitfromextensivesurgicalresection (epilepto-surgery). • Skin lesions– laser therapy (pulseddye laser treatment) • Glaukoma = oral carbonicanhydraseinhibitorsp.o. = surgical – goniotomy, (older) trabeculectomy • Vasculartrombosis(leptomeningealangiomatosis) – aspirin in daily dosis – preventionofstroke-likeepisodes

  48. Thank you

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