22201999 chromosomal disorders

8/2/2019 22201999 Chromosomal Disorders

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ChromosomalDisorders


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DefinitionsGene:smallestunitofasinglecharacteristicChromosome:structuralelementsinthecellnucleusthatcarrythegenesandconveygeneticinformationEachcell(exceptRBO)containallofthechromosomesfrombothparentsinthenucleus23pairsofchromosomescomefromeachparentAutosome:oneofthe22pairsofchromosomesthatisnotresponsiblefordeterminingthesexofthechildSexChromosome:XandYchromosomesresponsibleforsexdetermination


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ChromosomalDefectsAbnormalNumberMonosomy:onelessthanthediploidnumber(45)Trisomy:onemorethanthediploidnumber(47)

Mosaicism:somecellshavethecorrectnumberofchromosomesandsomehavemoreorlessthanthecorrectnumberofchromosomesAbnormalStructureDeletion:lossofachromosomalsegmentTranslocation:theoccurrenceofachromosomalsegmentatanabnormalsiteeitheronanotherchromosomeorinthewrongpositiononthesamechromosome


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PrenatalDiagnosisMaternalSerumAlpha-fetoprotein(MSAFP)Doneat1618wksgestationHighMSAFP:incorrectdates;multiplegestation;neuraltubedefects,abdominalwalldefects;renalanomalies;esophagealorintestinalobstructionsLowMSAFP:incorrectdates;chromosomaldefect(esp.Trisomy21)

Ultrasound


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AmniocentesisUsuallydoneat1618wksgestationFluidanalysismayrequireupto2-3wksCausuallydetermine:fetalsex,metabolicdisorders,chromosomalabnormalities

ChorionicVillusSampling(CVS)Usuallydoneat810wksgestationFetalcellanalysisusuallytakes2448hour


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NewbornCareHistoryFamilyHistory:anysimilarrelatives,frequencyofspontaneousabortionsPrenatalHistory:fetalactivity,maternalexposures,uterinemalformations


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NewbornAssessmentFace:configuration,spacingoffeature,locationoffeaturesHead:sizeandshapeofskull,fontanelEyes:structure,location,colorofirisEars:lowsetorcorrectlocation,skintagsNose:numberofnares,location,flattenedbridgeOral:sizeandshapeoftongue,mouth,jawNeck:webbing,extrafoldsHands&Feet:broad,square,polydactyly,abnormalcreasures,contractures,overridingfingersortoes


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FamilySupportCrisisGrieflossofperfectchildGeneticcounselingIdentifythenormal


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Trisomy21a.k.a.DownsSyndromeCausedbyanextrachromosome21

NormalKaryotype

Trisomy21(47,XY,+21)


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Trisomy21Incidence1:6501000livebirths,parentalagerelated75%abortspontaneouslySexro:3males/2femalesMostcommonautosomalchromosomaldisordercausingmentalretardation

RiskFactorsmaternalageParentalcarrieroftranslocation

PrenatalTestingTriplescreen(alpha-fetalproteindecreased,estrioldecreased,beta-HCGincreased)Ifpositive,amnioorCVSmaybeindicated


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ClinicalPresentationSize:small,20%areprematureSkull:shortandroundwithaflatocciput,separatedsuturesEyes:slantupwardandoutwardProminentepicanthalfoldMoon-shapedfaceBrushfieldsspotsCheeks:redPalate:narrowandshortNose:shortwithflatbri

Tongue:protrudes,tonguethrustingSkinloosearoundlateralanddorsalaspectsofneckHands:fingersareshort,handsaresquare,thumbsarelowset,separatedmorethanusualfromsecondfinger,5thfingerisshortandcurvesinward,single/bilateralsimeancreaseEars:low-set,posteriorlyrotatedears


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ClinicalPresentationUmbilicus:herniatedFeet:widespacebetweengreattoeand2ndtoe,deepcreasebetweengreattoeandthe2ndtoe,flatfeetHeart:VSDDuodenalatresiaMuscularhypotoniaRetardedpsychomotordevelopmentHyperlaxityofligaments

Velvety,looseadheringmottledskinininfancy,coarseskininadolescenceMouthfrequentlyopen/frequentlyopenmouthVisualand/orhearingimpairment


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PrognosisCongestiveheartfailured/tCHDUpperrespiratorytractinfectionsDevelopmentllydelayedMildlytoseverelymentallyretarded:IQrangesfrom2570Increasedriskforthyroidproblemsandleukemia


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Trisomy18a.k.a.EdwardsSyndrome,TrisomyE,Trisomy1618Causedbyanextrachromosome8

NormalKaryotype

EdwardsSyndrome(47,XY,+18)


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Trisomy18Incidence1:60008000livebirthsF>M(4:1)Mostdieinembryonicorfetallife

RiskfactorsIncreasedpaternalandmaternalage

PrenatalscreeningGoodindicatorisifinmaternalserumduringmidtrimesterhavelowhumanchorionicgonadotrophinandlowunconjugatedestriolUltrasoundIfanomaliesseen,amnioorCVSmaybeindicated


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3TypesofTrisomy18FullFormEverycellinthebodyhas3chromosome18insteadof2Severeform

MosaicFormSomecellshave3chromosome18andothershave2Lesssevereform

PartialFormInsomecellstheremaybeanextracopyofpartofchromosome18Severitydependentonanomalies


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ClinicalPresentationPrenatalhx:feeblefetalactivity,polyhydramnios,smallplacenta,singleumbilicalarteryPost-datesSGAWeight:lowbirthweightinterminfantWeakcryResponsosounddecreasedEars:lowsetand/orabnormalshapeMouth:micrognathia,microstomia,cleftlip,cleftpalateMentalretardationHeart:VSD,PDA,ASDFeet:rockerbottom,bigtoeshortenedanddorsiflexed,clubfeetCrossedlegsDiastasisrectiPectuscarinatumGUdefects:horseshoekidneys,hydronephrosis,polycystickidneys


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ClinicalPresentationHands:clenchedandwithflexedfingers(usuallywhereindexfingeroverlaps3rdand4thfingers),flexioncontractionofthetwomiddledigits,underdevelopedorabsentthumb,simiancrease,archesonsevenormorefingers,nailsunderdevelopedSyndactylyEyes:ptosisofoneorbotheyelids,epicanthalfolds

Head:abnormallyprominentocciput,microcephalyHernias:umbilical,inguinalRedundantskinfoldsesp.overthebackoftheneckMales:cryptorchidism


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Prognosis2030%dieduringthefirstmonth90%diebyageone1%chanceofsurvivingt0yrsHighmortalityrateiscausedbycongenitalheartmalformations,gastrointestinalandgenitourinaryanomalies,feedingdifficulties,andassociatedcentralnervoussystemdefectsthatproducecentralapnea.Althoughtheyfunctionwithseverehandicaps,allolderchildrenwithTrisomy18smile,laugh,interact,relatetotheirfamilies,andachievesomepsychomotormaturation.Mosaiccasesmayshowmilderphenotypicexpressionandprolongedsurvival.


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CareManagementNotreatmentbeyondsupportivecareNGorGTfeedingsOrthopedicmanagementiacmanagementGeneticcounselingParentalsupportApneamonitoring/O2ifneeded


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Trisomy13a.k.a.PatausSyndrome,13+Syndrome,1315DSyndrome,TrisomySyndromeCausedyanextrachromosome13

NormalKaryotype

Trisomy13(47,XX,+13)


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Trisomy13Incidence1:5000livebirthsMale=Female

RiskFactorsIncreaseswithmaternalandpaternalageIncreaseswithincreasedparityParentalcarrierofbalancedtranslocation

PrenatalScreeningUltrasoundIfanomaliesseen,amnioorCVSmaybeindicated


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ClinicalPresentationSeverementalandpsychomotorretardationEars:malformed,low-setHands:flexiondeformities;polydactyly,simiancrease,clenchedhandsHeart:VSD,PDA,ASD,rotationalanomalies(dextrocardia)Eyes:microphthalmos,colobomasofiris,cataracts,retinaldysplasia,closeset(mayfuseintoone)

Nose:broadandflattenedMouth:cleftlipandpalateHernias:umbilicalhernia,inguinalherniaKidneys:polycysticSkin:cutaneoushemangiomasHead:dermalsinusonscalp,microcephalyBrain:grossdefects,grandmalseizures,myoclonicjerks,seizures,holoprosencephaly


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ClinicalPresentationSkinloosearoundlateralanddorsalaspectsofneckSingleumbilicalarteryApneaenitaliaFemale:bicornate/septateuterusMale:cryptorchidism

Mouth:cleftlip,cleftpalateSpine:meningomyeloceleFeet:rockerbottomLow-birtweightOmphaloceleGIXRorUSmayrevealabnormalrotationofinternalorgans


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Prognosis82%diewithinthefirstmonth5-10%survivethefirstyearSurvivaltoadultoodrareCommondisordersifsurvivebeyond1monthofageSeverementalretardationFeedingdisabilitiesGErefluxSlowpostnaApneaKidneydefectsSeizuresDevelopmentaldisabilitiesScoliosis


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CareManagementNotreatmentbeyondsupportivecareParentalsupport


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TurnersSyndromea.k.a.TS,MonosomyX,GonadalDysgenesis,Bonnevie-UllrichSyndrome,XOSyndromeIstheabsenceofonesetofgenesfromtheshortarmofoneXchromosome

NormalKaryotype

TurnersSyndrome(45,X)


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TurnersSyndromeIncidence1:2000-3000live-bornfemalesFemalesonlyaffected98%ofpregnancieswithTspontaneouslyabort10%ofpregnanciesthatspontaneouslyaborthaveTS

RiskFactorsIncreasedpaternalageMotherwithmosaicordeletionalTurnersSyndrome

SHOXgeneassociationSHOXgeneprovidesinstructionsformakingaproteinthatregulatesactivityofothergenes


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ClinicalPresentationShortstature;meanbirthweight2.9kg;averageheight:47WebbedneckLowposterhairlineMicrognathiaEars:low-set,sometimesmalformed,pronetootitismediaWidelyspacedhypoplasticnipplesonashield-shapedchestIncreasedcarryingangleattheelbowHeart:coarctationoftheaorta,aorticvavularstenosis,bicuspidaorticvalve,aorticdissectionEye:ptosis,strabismus,amblyopia,cataracts,epicanthalfolds,dryeyes,red-greencolorblindnessCongenitalhipdislocationAbnormalgrowthpatternsCongenitallymphedemaofhandsandfeet


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ClinicalPresentationAbsentorretardeddevelopmentofsecondarysexualcharacteristicsthatnormallyappearatpubertyAbsentmenstruationAbsenceofnormalvaginalmoistureinfertilityGonadaldysplasiaHorseshoekidneyUnilateralrenalagenesisIntelligence:notatriskformentalretardation,betterverbalthenvisuospatialabilitiesBroadnasalbridge


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PrognosisFemalesarebasicallynormaldespitefailureofsexualdevelopmentAtriskforMiddleearinfectionsScoliosisArthritisCataractsHashimotostabnormalitiesHighbloodpressureObesityDiabetesmellitusOsteoporosisKeloidformation


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CareManagementEarlySupportivecareSurgerytocorrecttreatabledefects

LateGrowthhormonetherapyEstrogenreplacementtherapyCounselingandpsychiatricsupport25%havesomeovarianfunctionandcanmenstruateandbecomepregnantOtherscanhavechildrenusingdonoreggsandin-vitrofertilization


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VATERAssociationVATER=VertebralanomaliesAnalatresiaTracheo-Esophagealfistula,RadialandrenaldysplasiaIncidenceUnknown

EtiologyUnknown


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ClinicalPresentationThreeormoreofthefollowingdefectsmustbepresent:VertebralanomaliesAnalatresiawithorwithoutfistulaTEFwithEARadialdyslasia,includingthumborradialhypoplasia,polydactyly,andsyndactylyRenalanomalySingleumbilicalartery


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PrognosisFTTPossibilityofnormallifeafterslowmentaldevelopmentduringinfancy

CareManagementSupportivecareSurgery:surgicalcorrectionofanomalies


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22201999 chromosomal disorders

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