Birth defect Congenital malformation Congenital anomaly (Hereditary) abnormality

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1Causes of Malformations(Teratogenesis or Dismorphology)

???Presented by Dr Sadatinejad, Seyyed Mohsen,student of Medicine from Iran,Kashan 19/12/20122Birth defectCongenital malformationCongenital anomaly(Hereditary) abnormalityTypes of Abnormalities :MalformationDisruptionsDeformationsSyndromesMinor anomaliesMajor anomalies

Principles of Teratology1- ( ) 2- (Developmental stage at the time of exposure)3- (Dose and duration of exposure to a teratogen)4- : 5- :

Hereditary (Genetic) causes 15-18%Environmental factors 7-10%Multifactorial 25%Unknown 50%

6First week (Resistant period)Embryonic periodMaximum susceptibility (organ morphogenesis)Fetal PeriodLowered Susceptibility (functional derangement)

Genetic factors1- (Numerical Chromosomal Anomalies)) (Polyploidy)Triploidy 69 Tetraploidy 92 ) (Aneuploidy) 13 (Patau syndrome) 18 (Edwards syndrome) 21 (Down syndrome) (Klinfelter syndrome-XXY) Triple X (Superfemale) (Turner syndrome- XO) 8Patau Syndrome1/20000


Edwards Syndrome1/5000

Maternal nondisjunction (95%)MosaismTranslocationDown syndrome

MonosomyNondisjunction in sperm 80%Struc XNondisjunction in mitosis (Mosaism)

2- (Structural Chromosomal Anomalies)IsochromosomeCrossing over : Translocation21,13,14, 15 in Down syndromePartial Deletion Cri du chat 5(microcephal, mental, cardiovas) Microdeletion Angelman 15 (speech, mental, movement) Prader- willi 15 (fatty, mental, hypogonad)Inversion133- (Gene Mutation Anomalies)

Marphan syndromeCrigler-Najjar syndromeRoberts syndromeAlport syndromeAarskog-Scott syndromeSavant syndrometreacher-collins syndromeNiemannPick diseaseCystic FibrosisDMD

14 . 15 . .

. . . (:Crigler-Najjar_syndrome) . .

(:Roberts syndrome) . . (:Alport syndrome) IV . . -(:Aarskog-Scott syndrome) . . . X .

(:Cystic Fibrosis) (:CF) CF CFTR . CF .CFTR CAMP . CFTR . CFTR () CF - . . . . . (:Savant syndrome)[] . . . Treacher Collins . . (down slanted anti-mongoloid) . . . . (ramus) . . ( ) . .

Environmental factorsInfectious Agents (& other disease)

Drugs Agents (& Hormonic Agents)

Chemical Agents

Physical Agents

15A) Viral infectionsRubella virus (German Measles) 1month-From placenta- atrioventricular septsl defect, cataract. Weight Cytomegalovirus(CMV) From Placenta,Cervix,Vagina (& Lactation) - microephaly, deafness, mental retardation, hepatospleenomegally ,cardiac defect,cerebral calcification, blue spot on skin Herpes simplex virus(HSV) From Placenta,Vagina(85%)- Defect in CNS,liver, pancreas,ren,suprarenal glands, infection on skin, Eyes or mouth no treatment=40-50% deathVaricella-zoster virus(VZV) First 3 month-From Placenta- limb hypoplasia & parasis., hydrocephaly. Mental retardation, cataractHIV After 35th week- Systematic Chronic infection(fangus,bacterial,viral,protozoan)Infectious Agents

16Infectious AgentsB) Nonviral infectionsToxoplasma in each three munth - death,microcephaly,hydroceohaly,cerebral calcification Treponema pallidum Syphilis, rhinitis,eye defect(cataract),icterus,abnormal teeth, splenohepatomegaly

17 DeseaseDiabetes Coudal disgenesis, deathPKUmental retardation, microcephaly, cardiac defect Nutrient deficiency Iodine deficiency coused cretinismObesityONTD, cardiac defect, Hypoxy

18Drugs AgentsCategory X drugs

Category D drugs

19Category X drugs

Thalidomide Aminopterin methotrexateBusulfan Phenytoin Triazolam Warfarin IsotretinoinClomiphenDiethylstilbestrol Ethisterone Norethindrone Nicotine Alcohol

20Category X drugs


antinauseant drug limb defect (Amelia,Meromelia)Cardiac defectGIT atresyOptic & otic defect

21Category X drugs


22Category X drugs

Aminopterin MethotrexateBusulfan

Used in chemotererapy Dawerfism Myelomeningocele palate clef Growth retardation ophtalmic defect

23Category X drugs

Aminopterin MethotrexateBusulfan

Used in chemotererapy Dawerfism Myelomeningocele palate clef Growth retardation ophtalmic defect

24Category X drugs


Antileptic drug microcephalyGrowth & mental retardationpalate clefFinger & nail HypoplesiaSkull defect

25Category X drugs


Anti couagulant drugMental retardation microcephalyoptic n. atrophy Fetal bleeding

26Category X drugs


Non-steroidal drug Used for stimulus ovulation

Maybe Malformatin


Category X drugs

Retinoids (vitamin A)Used for Cystic aknesevere craniofacial defects cardiac defectsneural tube defects (NTD)Palate cleft

tretinoin (Retin-A)

isotretinoin, 13-cis-retinoic acid

28Category X drugs


Mental retardationWheight lossFetal HypoxyPremature Parturition

29Category X drugs


Fetal Alcholic Syndrome (FAS)Mental retardationmicrocephalyCardivascular defectLimb & Face malformationHairsutism

30Category D drugs

Tetracycline doxycycline Streptomycin Phenobarbital PentobarbitalValsuroic acid Diazepam lorazepamLithium Hydrochlorothiazide31Category D drugs

Phenobarbital & Pentobarbital

paliative drugFetal malformation

32Category D drugs

Diazepam, Lorazepam , Chlorodiazepoxide antianxiety drug palate & lip clef specially in first 3 munth

33Category D drugs

Lithium ,Phenothiazine

AntiedepressiveCardioVascular defect34Chemical Agents(heavy metals)Organic mercury Blindness, deaf, cerebral pulsy (c.p)Leadmental retardation, death of fetusPoly chlorin biphenyil & Pentobarbital mental retardation, gingiva hyperplasia, exophthalmos, skull calcification, brown pigment in skinPotassium iodideused as contrastment substance. mental retardation, goiter

35 :- - - - - - - - - - -

Physical AgentsIonizing RadiationAcute high dose (over 250 rads) Microcephay,spina bifida,palate cleft, limb defectHyperthermiaanencephaly,spina bifida, mental retardation, facial malformation, cardiac defect, limb defect

Male-mediated TeratogenesisChromosomal defects & Mutation in germ cells

Environmental agent : transmission of paternal mediated toxicity through seminal fluidUltrasonographyMaternal Serum Screening (AFP,hCG) AFP : Trisomy- NTD,GIT atresia,amniotic bandAmniocentesisChorionic Villus Sampling (CVS)Prenatal DiagnosisAlpha-fetoprotein38Fetal TransfusionFetal Medical TreatmentFetal SurgeryStem Cell Transplantation and Gene TherapyBefor 18th week (activation of immune system)Fetal Therapy