染色体异常课件

染色體異常鄭博仁副教授染色體異常鄭博仁副教授1 人類正常染色體組成於1956年正式確立,第一批染色體異常(Downs，Tunners，Klinefelters症候群)則定義於1959年。自此，由於培養與檢驗之遺傳科技日益精進，因染色體異常導致的數百種異常也逐一被發現。人類正常染色體組成於1956年正式確立2染色体异常课件3染色体异常课件4染色体异常课件5染色体异常课件6染色体异常课件7三倍體 17Nail hypoplasiaFetal wastage(95%)Hyotonia,followed by hypertonia,apnea,seizuresMicrophthalmia死胎 5Chromosome typesWilliams SyndromeMultiple pigmented neviDS:Major MalformationsSlanting palpebral fissures,small dysplastic ears,flattened faciesSkeletal anomalies:polydactyly,talipes equinovarusMales in institutions for the mentally retarded-1/100Advanced maternal age effectCub foot,cataracts,imperforate anus,cleft lip/palateMCA/MR caused by an extra copy of 18Otherwise normal phenotype5-10%(parental translocation)Round face,hypertelorism,epicanthal folds,downward slanting of palpebral fissuresMicrocephaly,bitemporal depression,long philtrum,thin upper lip,mild micrognathia,ear dysplasia,anteverted nares三倍體 8定義：?整倍體（Euploid）染色體數目是單倍體的倍數 （2n）?多倍體（Polyploid）染色體數目超過二倍體（3n,三倍體）?非整倍體（Aneuploid）染色體數目非單倍數的倍數 （2n1三體症，2n1單體症）?嵌合體（Mosaic）出現來自同一配子的二種不 同細胞來源（46XX/45X，Turners嵌合體）?交移體（Chimaera）出現來自二個配子融合形成 的二種不同細胞來源 （46XX/46XY，真性陰陽人）定義：整倍體（Euploid）染色體數9染色体异常课件10染色体异常课件11染色體報告形式?染色體總數後列出性染色體形式46,XX ，正常女性47,XXY ，Klinefelters症男性47,XXX ，三X症女性?增加或缺少的染色體以”或”表示 47,XY,21 ，21三染色體男性（Downs症）46,XX,12 p ，12染色體短臂多出一段不明染 色體?嵌合體列出所有的細胞來源46,XX/47,XX,21 ，Downs嵌合體症46,XY/47,XXX/45,X ，Turnes/三X嵌合體症?描述構造上的異常，指出p，q及異常的部位46,XY,del 11(P13)11染色體短臂的13顯帶處缺失46,XX,t(X;7)(P21;q23)X與7染色體在P21及q23顯帶處 裂開而移位染色體報告形式染色體總數後列出性染色體形式46,XX 12染色体异常课件13染色体异常课件14染色体异常课件15染色体异常课件16染色体异常课件17自然流產及死胎的染色體異常發生率%自然流產 所有 50 12週以內 60 1220週 20死胎 5自然流產及死胎的染色體異常發生率 18Otherwise normal phenotypeHypercalcemia/hypercalcinuriaHirschprung diseaseTranslocation trisomy(4%)Proportionate short statureKlinefelter Syndrome:HypogonadismThree active X chromosomes early in embryonic development(prior to X inactivation)Two of the three X chromosomes are inactivated.Advanced maternal age effectMicro/retrognathiaDeletion of a WH probe signalMicrocephalyMales in institutions for the mentally retarded-1/100Klinefelter Syndrome:BackgroundDel(5p)syndromeAbsent secondary sex characteristicsDel(5p)syndromeMultiple pigmented nevi47,XXX(1/1,000 female births)Microcephaly,trigonocephaly,glabellar hemangioma,punched-out scalp lesionThe great majority(99%)of 45,X conceptus are lost prenatally.自然流產的染色體異常種類%三體症 52X 單體症 18三倍體 17移位 2-4Otherwise normal phenotype自然流產19新生兒染色體異常比例%所有 91常染色體三體症 14常染色體重組 平衡性 52 非平衡性 6性染色體異常 19新生兒染色體異常比例 20常見的染色體異常常染色體 21三體症Downs症 18三體症Edwards症 13三體症Pataus症性染色體 XO Turners症 XXX 三X症 XXX Klinefelters症 XYY XYY男性常見的染色體異常常染色體21染色体异常课件22染色体异常课件23染色体异常课件24Down Syndrome(Trisomy 21)唐氏症(蒙古痴呆症)MCA/MR caused by an extra copy of chromosome 21First described by Langdon Down in 1866Discovery of +21 by Lejeune in 1959Down Syndrome(Trisomy 21)唐氏症25DS:EpidemiologyIncidence:1/800 to 1/1,000 live birthsPrevalence:1/3,000 in general population,reflecting high infant mortality rateAdvanced maternal age effectDS:EpidemiologyIncidence:1/26DS Fetuses:Natural HistoryHighly lethal in fetal life(65%of conceptuses aborted)Recognizable fetal phenotype:IUGR,thickened nuchal fold,septal cardiac defects,duodenal atresia,simian crease,clinodactyly,&short cordDecreased motor activityDS Fetuses:Natural HistoryHig27染色体异常课件28Psychosocial/behavioral problemsDel(7)(q11.Psychosocial/behavioral problemsAntimongoloid slantTrisomy 13(Patau Syndrome)Hirschprung diseaseGenu valgumFISH:Trisomy 21Mosaics or translocations(20%)Abnormal finger grasping pattern,increased digital arches,rocker-bottom feet,short sternumMother with 21/22 carrier-6%46,XY/47,XXY(15%)染色體總數後列出性染色體形式46,XX ，正常女性47,XXY ，Klinefelters症男性47,XXX ，三X症女性Deletion of 4pIncidence in male prison populations(1/30)Trisomy 18 fetusDe novo(90%)所有 50Abnormal earsShort philtrumWHS KaryotypeTranslocation trisomy(4%)Cardiac/genitourinary/skeletal anomaliesDel(4p)syndromeEpicanthal foldsKlinefelter Syndrome:HypogonadismCardiac/genitourinary/skeletal anomaliesDistinct finger grasping patternDel(7)(q11.69,XXY(60%)Absent secondary sex characteristicsEpicanthal foldsProtruding tongueShort philtrumRecurrence risk-not increasedHypercalcemia/hypercalcinuriaLearning/speech disabilitiesTriploidy is a frequent cause of fetal wastage(20%)during 1st/2nd trimester.Most frequent sex chromosome abnormality present at birth in femalesFemale type distribution of pubic hairXYY SyndromeMost cases(de novo)DS:Cardinal SignsHypotoniaSloping forehead,brachycephalySlanting palpebral fissures,small dysplastic ears,flattened faciesExcess nuchal skinSimian crease with dysplastic middle phalanges of 5th fingerHyperextensible jointsDysplastic pelvisPsychosocial/behavioral proble29DS:InfantSloping foreheadUpslanting eyesEpicanthal foldsFlat nasal bridgeSmall noseProtruding tongueSmall chinSmall earsProximated nipplesDS:Infant30DSBrachycephalySloping foreheadWoolley signFlat nasal bridgeSmall noseProtruding tongueCutis mamorataDSBrachycephaly31DS childUpslant eyesBrushfield spotsEpicanthal foldsFlat nasal bridgeSmall noseOpen mouthProtruding tongueSmall chinSmall earsDS child32DS EarTypical DS small earOverfolded helixDS EarTypical DS small ear33DermatoglyphicsDermatoglyphics34DS HandTransverse palmar crease(simian crease)ClinodactylyDS HandTransverse palmar creas35染色体异常课件36DS:AdultMRUpslanting eyesMid-facial hypoplasiaMandibular prognathismDS:Adult37DS:Major MalformationsCongenital heart disease(29%of newborn;64%of necropsies)AV canal/endocardial cushion defect(most common),VSD,ASD,TOF,PDA,othersDuodenal obstruction(2-3%)Hirschprung diseaseOthersCub foot,cataracts,imperforate anus,cleft lip/palateDS:Major MalformationsCongeni38DS:Growth&DevelopmentDevelopmental delay(MR)Atlantoaxial joint instabilityMales:Infertile due to testicular interstitial fibrosis and hypoplasia of seminiferous tubulesFemales:about 1/2 of offspring with Down syndromeDS:Growth&DevelopmentDevelo39DS:Immune System&AgingIncreased incidence of hypothyroidism,thyroiditis,diabetes mellitus,and leukemia(10-to 30-folds)Depressed immune systemPremature aging(Alzheimer)DS:Immune System&AgingIncre40染色体异常课件41染色体异常课件42染色体异常课件4347,XYY SyndromeSecondary sexual characteristicsCardiac/genitourinary/skeletal anomaliesGenu valgumXO Turners症Microcephaly69,XYY(99%)of 45,X conceptus are lost prenatally.MicrocephalyTurner Syndrome:EpidemiologyPremature aging(Alzheimer)A common cause of primary hypogonadism in malesRound face,hypertelorism,epicanthal folds,downward slanting of palpebral fissuresShort philtrumMost die within 1st few days of life.Abnormalities may result from:Incidence:1/2,500-1/5,000 liveborn females%MCA/MR caused by an extra copy of 18Translocation trisomy(4%)Cubitus valgus性染色體異常 1947,XYY Syndrome44Trisomy 21 KaryotypeTrisomy 21 Karyotype45活產及羊膜穿刺檢查唐氏症發生率孕婦年齡(生產時 活產發生率 羊膜穿刺術發生率或羊膜穿刺術時)所有年齡 650分之1 30歲 900分之1 35歲 385分之1 256分之1 36歲 305分之1 200分之1 37歲 240分之1 156分之1 38歲 190分之1 123分之1 39歲 145分之1 96分之1 40歲 110分之1 75分之1 44歲 37分之1 29分之1 活產及羊膜穿刺檢查唐氏症發生率孕婦年齡(生產時 46染色体异常课件47I(21q)KaryotypeI(21q)Karyotype48染色体异常课件49染色体异常课件50染色体异常课件51染色体异常课件52染色体异常课件53染色体异常课件54FISH:Trisomy 21FISH:Trisomy 2155DS:Cytogenetic BasisFull trisomy(94%)Translocation trisomy(4%)Translocation between 21&other chromosomeMosaic trisomy(2%)Most commonly due to maternal non-disjunction(95%by molecular studies)21q22 to qter is responsible for the phenotypeDS:Cytogenetic BasisFull tris56DS:Genetic Counseling(Recurrence Risk)Full trisomy 21(irrespective of maternal age)-1%Siblings,nieces,nephews,a aunts,or uncles of the proband with trisomy 21 probably no increased riskMother with balanced D/G translocation-10%Father with balanced D/G translocation-4%Mother with 21/22 carrier-6%Father with 21/22 carrier-3%Parent with 21/21 carrier-100%A DS child with de novo translocation-1%DS:Genetic Counseling(Recurr57染色体异常课件58染色体异常课件59染色体异常课件60染色体异常课件61染色体异常课件62染色体异常课件63染色体异常课件64染色体异常课件65Deletion of a WH probe signal所有年齡 650分之1Turner Syndrome:Cytogenetic BasisDel(5p)syndromeTrisomy 18(Edwards Syndrome)45,X represents 15-20%of chromosome abnormalities seen among spontaneous abortions.Woolley signSevere cystic hygromaEach additional X chromosome is accompanied by increased mental retardation&physical abnormalitiesGrowth Chart for Turner SyndromeMicrophthalmia嵌合體（Mosaic）出現來自同一配子的二種不 同細胞來源（46XX/45X，Turners嵌合體）Prevalence:one in 2,500-10,000 femalesFull trisomy 21(irrespective of maternal age)-1%Overfolded helixGrowth hormone therapy染色體總數後列出性染色體形式46,XX ，正常女性47,XXY ，Klinefelters症男性47,XXX ，三X症女性Epidemiology:1/3,000 live birthsDescribed by Turner in 1938Renal/GI anomalies(cystic kidneys;TE fistula)Objectives:Students are required to study and understandDeletion of a WH probe signal66染色体异常课件67染色体异常课件68羊膜穿刺判讀錯誤羊膜穿刺判讀錯誤 新光判賠七百多萬新光判賠七百多萬婦人朱秀蘭高齡懷孕，到台北新光醫院作羊膜穿刺篩檢，因醫院僱用非專業的檢驗員判讀資料錯誤，致生下患有唐氏症的男孩，朱女經過八年訴訟，最近獲得確定勝訴判決，最高法院前天判決新光醫院應賠償朱女七百廿五萬餘元。羊膜穿刺判讀錯誤 新光判賠七百多萬婦人朱秀蘭高齡懷孕，到台69染色体异常课件70染色体异常课件71Trisomy 18(Edwards Syndrome)MCA/MR caused by an extra copy of 18Epidemiology:1/3,000 live birthsNatural history:Fetal wastage(95%)Intrauterine growth retardationPolyhydramniosSmall placenta with single umbilical artery90%die before 1 year of ageSevere growth and mental retardationTrisomy 18(Edwards Syndrome)M72染色体异常课件73Trisomy 18:Cardinal Signs Hyotonia,followed by hypertonia,apnea,seizuresMicrocephaly,prominent occiputHypertelorism,epicanthal folds,microphthalmia,iris coloboma,micro/retrognathia,low set/malformed ears,choanal atresiaCardiac defects(polyvalvular,VSD)Renal/GI anomalies(cystic kidneys;TE fistula)Abnormal finger grasping pattern,increased digital arches,rocker-bottom feet,short sternumTrisomy 18:Cardinal Signs Hyo74Infant with trisomy 18MicrocephalyHypertelorismMicrophthalmiaMicro/retrognathiaLow set,malformed earsShort sternumAbnormal finger grasping patternInfant with trisomy 18Microcep75Trisomy 18 fetusArthrogryposisDistinct finger grasping patternTrisomy 18 fetusArthrogryposis76Trisomy 18ArthrogryposisAbnormal finger grasping patternNail hypoplasiaIncreased number of digital archesTrisomy 18Arthrogryposis77Trisomy 18Rocker-bottom feetTrisomy 18Rocker-bottom feet78染色体异常课件79染色体异常课件80染色体异常课件81染色体异常课件82Trisomy 13(Patau Syndrome)Epidemiology:1/6,000 live birthsCytogenetics:Full trisomy(80%)Mosaics or translocations(20%)Natural history:90%die before 1 year of ageFTT,hypotonia,deafness,seizuresSevere psychomotor retardationTrisomy 13(Patau Syndrome)Epi83染色体异常课件84Trisomy 13:Cardinal SignsCraniofacial:Microcephaly,trigonocephaly,glabellar hemangioma,punched-out scalp lesionHypertelorism,anophthalmia/microphthalmia,coloboma of iris/retina,cleft lip/palate,micro/retrognathiaCNS:holoprosencephaly spectrumCardiac/renal/GI anomalies:VSD,multicystic kidneys,omphaloceleSkeletal anomalies:polydactyly,talipes equinovarusTrisomy 13:Cardinal SignsCran85Trisomy 13MicrocephalyMicrophthalmiaCleft lip/palateHoloprosencephalyShort neckPolydactyly86Trisomy 13Microcephaly86Trisomy 13Infant with trisomy 13Scalp defectPolydactylyTrisomy 13Infant with trisomy 87染色体异常课件88染色体异常课件89染色体异常课件90染色体异常课件91染色体异常课件92染色体异常课件93染色体异常课件94Sex Chromosome AnomaliesTurner syndromeKlinefelter syndromeTrisomy X syndromeXYY syndromeSex Chromosome AnomaliesTurner95染色体异常课件96Turner SyndromeDescribed by Turner in 1938Prevalence:one in 2,500-10,000 femalesPhenotypic femaleProportionate short statureNormal intelligenceSexual infantilism&ovarian dysgenesisTurner SyndromeDescribed by Tu97Turner Syndrome:Sexual infantilism&ovarian dysgenesisThe ovaries develop normally until the 15th week of gestation,but then ova begin to degenerate and disappear,so that at birth they are represented by streaksPrimary amenorrhea(exception 5%)InfertilityAbsent secondary sex characteristicsLow estrogenHigh gonadotropinsTurner Syndrome:Sexual infant98Turner Syndrome:Characteristic FaciesAntimongoloid slantPtosisStrabismusHigh-arched palatePosteriorly rotated earsTurner Syndrome:Characterist99Turner Syndrome:Lymphatic ObstructionWebbed neckLow posterior hair lineRedundant skin on the napeCystic hygromaRotated earsLymphedema of hands/feetNail hypoplasiaTurner Syndrome:Lymphatic Ob100染色体异常课件101染色体异常课件102Turner SyndromeShort neckWebbed neckLow posterior hair lineAbnormal earsTurner SyndromeShort neck103Turner Syndrome:FetusSevere cystic hygromaTurner Syndrome:FetusSevere c104Turner SyndromeLymph edemaNail hypoplasiaTurner SyndromeLymph edema105Turner SyndromeNail hypoplasiaTurner SyndromeNail hypoplasia106Turner Syndrome:Skeletal FeaturesShort statureShort neckCubitus valgusShort metacarpalsMadelung deformityScoliosisGenu valgumTurner Syndrome:Skeletal Feat107Growth Chart for Turner SyndromeGrowth Chart for Turner Syndro108Turner Syndrome:Miscellaneous DefectsShield-like chest,increased inter-nipple distance(optical illusion in some cases)Multiple pigmented neviCardiovascular anomalies/hypertension(COA most common)Renal anomaliesHorse-shoe/ectopic/absent kidneyUreteral duplications)Hearing lossTurner Syndrome:Miscellaneou109Turner Syndrome:ChestShield-like chestIncreased inter-nipple distanceTurner Syndrome:ChestShield-l110Turner Syndrome:Associated DisordersHashimoto thyroiditisHypothyroidismCrohn diseaseGastrointestinal bleeding(telangiectasia)Turner Syndrome:Associated D111Turner Syndrome:EpidemiologyIncidence:1/2,500-1/5,000 liveborn females45,X represents 15-20%of chromosome abnormalities seen among spontaneous abortions.The great majority(99%)of 45,X conceptus are lost prenatally.Many chromosomal mosaicism or confined placental mosaicism do survive to term.Turner Syndrome:Epidemiology112Turner Syndrome:Karyotype(45,X)Turner Syndrome:Karyotype(45113Monosomy X:MechanismMonosomy X arises from non-disjunction80%of cases have only maternal X chromosome,an error occurred in spermatogenesis or post-fertilizationMonosomy X:MechanismMonosomy 114Turner Syndrome:Cytogenetic BasisKaryotypes45,X(50%)Mosaics(30-40%)Iso(Xq),r(X),iso(Xp)In general,del(Xp)is associated with the Turner phenotype,whilst del(Xq)alone produce streak ovaries without the associated dysmorphic features(Turner stigmata)Turner Syndrome:Cytogenetic 115Turner Syndrome:ManagementPsychosocial approachWebbing resection(cosmetic)Sex hormone replacementSecondary sexual characteristicsStatureGrowth hormone therapyStatureGenetic counselingRecurrence risk-not increasedTurner Syndrome:ManagementPsy116染色体异常课件117Klinefelter Syndrome:BackgroundIn 1942,Klinefelter et al.reported 9 men who had:Enlarged breastsSparse facial and body hairSmall testesInability to produce spermIn 1959,men with Klinefelter syndrome were discovered to have 47,XXY.Klinefelter Syndrome:Backgrou118Klinefelter Syndrome:EpidemiologyIncidenceBirth 1/1,000 male birthsMales in institutions for the mentally retarded-1/100Infertile males-1/10Chromosome types47,XXY(majority)46,XY/47,XXY(15%)48,XXXY,48,XXYY49,XXXXY,49,XXXYYKlinefelter Syndrome:Epidemi119Klinefelter Syndrome:KaryotypeKlinefelter Syndrome:Karyotyp120染色体异常课件121Klinefelter Syndrome:Growth/DevelopmentTall with disproportionately long arms/legsPoorly developed secondary sex characteristicsLearning/speech disabilitiesPsychosocial/behavioral problemsSubnormal intelligenceKlinefelter Syndrome:Growth/D122Klinefelter Syndrome:A ChildSlightly long arms and legsOtherwise normal phenotypeKlinefelter Syndrome:A ChildS123Klinefelter Syndrome:HypogonadismA common cause of primary hypogonadism in malesGynecomastia(1/3),with increased risk for breast cancer(20X)Small testes(10 ml),sterility(most patients),secondary to atrophic seminiferous tubulesKlinefelter Syndrome:Hypogon124Klinefelter syndrome:GynecomastiaKlinefelter syndrome:Gynecoma125Klinefelter Syndrome:External GenitaliaFemale type distribution of pubic hairTesticular dysgenesisKlinefelter Syndrome:External126Klinefelter syndrome:ManagementAndrogen therapy(testosterone injection)for hypogonadismMastectomy for gynecomastiaMultidisciplinary team approachSpeech impairmentsAcademic difficultiesPsychosocial/behavioral problemsGenetic counselingRecurrence risk-not increasedKlinefelter syndrome:Manageme127Trisomy X SyndromeFirst described by Jacobs et al.in 1959Most frequent sex chromosome abnormality present at birth in females47,XXX(1/1,000 female births)Trisomy X SyndromeFirst descri128Triple X Syndrome:OriginMost 47,XXX conceptions result from maternal nondisjunction at meiosis I(AMA).Two of the three X chromosomes are inactivated.Abnormalities may result from:Three active X chromosomes early in embryonic development(prior to X inactivation)Genes on the X chromosome that escape inactivationTriple X Syndrome:OriginMost 129Triple X Syndrome:PhenotypeBenign phenotypePhysically normalLate pubertyMenstrual irregularityMajority are fertileSterilityMild mental retardation(15-25%)Triple X Syndrome:PhenotypeBe130Trisomy X:Karyotype(47,XXX)Trisomy X:Karyotype(47,XXX)131Triple X SyndromeSlender body habitusTriple X SyndromeSlender body 132染色体异常课件133Triple X Syndrome:Genetic CounselingA small but slightly increase risk of XXX daughter or XXY son of an XXX motherRecurrence risk not increased unless mother is a 47,XXX or mosaicPertinent to offer prenatal diagnosisTriple X Syndrome:Genetic Cou134Poly X SyndromesFemales with 4 or 5 X chromosomesEach additional X chromosome is accompanied by increased mental retardation&physical abnormalities48,XXXX49,XXXXXPoly X SyndromesFemales with 413547,XYY SyndromeIncidence:one in 1,000 malesArise through nondisjunction at paternal meiosis IIIncidence in male prison populations(1/30)47,XYY SyndromeIncidence:one 136XYY KaryotypeXYY Karyotype13747,XYY SyndromeNormal birth length and weightTall when olderSubnormal intelligenceSexual orientation:heterosexualNormal fertilityMinor behavioral disorders(hyperactivity,ADD,learning disabilities)Predisposition to violent,criminal behavior(controversy!)47,XYY SyndromeNormal birth le138XYY SyndromeTall statureOtherwise normal phenotypeXYY SyndromeTall stature139Triploidy SyndromeTriploidy is a frequent cause of fetal wastage(20%)during 1st/2nd trimester.Most die within 1st few days of life.Incidence:1/2,500 births69,XXY(60%)69,XXX(37%)69,XYY(3%)Diploidy/triploidy mosaicismMilder phenotypeTriploidy SyndromeTriploidy is140染色体异常课件141Triploidy“Cracked egg-shell”skullDistinctive facies(beaked nose,small chin,low-set/malformed ears)Woolly hairTriploidy“Cracked egg-shell”s142TriploidySyndactyly of fingers(3-4)Syndactyly of toes(3-4)TriploidySyndactyly of fingers143染色体异常课件144Objectives:Students are required to study and understandClassic deletion syndromes(Cri-du-chat,Wolf-Hirschhorn)Microdeletion syndromes(Williams,Miller-Dieker)Objectives:Students are requi145Classic Deletion SyndromesDel(4p)syndrome Del(5p)syndromeClassic Deletion SyndromesDel(146Del(4p)(Wolf-Hirschhorn Syndrome)Deletion of 4pDe novo(90%)Parental translocation or mosaicism(10%)IUGR,microcephaly,microphthamia,scalp defectsCharacteristic“Greek warrior helmet”facies,short philtrumCardiac/genitourinary/skeletal anomaliesSevere psychomotor retardationDel(4p)(Wolf-Hirschhorn Synd147WHS KaryotypeDel(4p)WHS KaryotypeDel(4p)148WHS-FISHDeletion of a WH probe signalWHS-FISHDeletion of a WH probe149WHS FaceMicrocephalyMRCharacteristic facies“Greek warrior helmet”Short philtrumWHS FaceMicrocephaly150染色体异常课件151Del(5p)(Cri Du Chat Syndrome)Incidence:1/50,000 live birthsA distinct,shrill,cat-like cry(secondary to hypoplastic larynx)Mental retardation,hypotonia,microcephalyRound face,hypertelorism,epicanthal folds,downward slanting of palpebral fissuresOther defects:CHD,simian creaseMost cases(de novo)5-10%(parental translocation)Del(5p)(Cri Du Chat Syndrome152染色体异常课件153CCS KaryotypeDel(5p)CCS KaryotypeDel(5p)154CCS Face/CryA round faceHypertelorismEpicanthal foldsCat-like cryCCS Face/CryA round face155Microdeletion SyndromesWilliams syndromeMiller-Dieker syndromeMicrodeletion SyndromesWilliam156Williams SyndromeElfin faciesFull cheeks/lips,long/smooth philtrum,broad foreheadDD,MROverly friendly personalitySupravalvular aortic stenosisHypercalcemia/hypercalcinuriaMusculoskeletal abnormalitiesDel(7)(q11.2)Williams SyndromeElfin facies157染色体异常课件158染色体异常课件159染色体异常课件160Miller-Dieker SyndromeLissenc