causes of malformations ( teratogenesis or dismorphology )
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Causes of Malformations(Teratogenesis or
Dismorphology)? ??
Presented by Dr Sadatinejad, Seyyed Mohsen,student of Medicine from Iran,Kashan 19/12/2012
Birth defect
Congenital malformation
Congenital anomaly
(Hereditary) abnormality
Types of Abnormalities :
• Malformation• Disruptions• Deformations• Syndromes
• Minor anomalies• Major anomalies
Principles of Teratology- پاسخ )آسیب پذیری( جنین و مادر به عامل تراتوژن1 - مرحله تکاملی جنین2
)Developmental stage at the time of exposure(- دوز و مدت زمان تماس با عامل تراتوژن3
(Dose and duration of exposure to a teratogen)- طریقه عمل تراتوژن : تغییرات در سطح سلولی و مولکولی4- نتیجه تراتوژن : مرگ، ناهنجاری، عقب ماندگی رشد، بیماری های 5
عملکردی
Hereditary )Genetic( causes 15-18%Environmental factors 7-10%Multifactorial 25%Unknown 50%
First week )Resistant period( Embryonic period
Maximum susceptibility )organ morphogenesis( Fetal Period
Lowered Susceptibility )functional derangement(
Genetic factors- اختالالت تعدادي كروموزوم 1•
)Numerical Chromosomal Anomalies()Polyploidyالف) پلي پلوئيدی (•
Triploidy 69 يك تخمك هاپلوئيد با دو اسپرم یا تخمک دیپلوئیدبا یک اسپرم
Tetraploidy 92 اولين كليواژ )Aneuploidyب) آنوپلوئيدی (•تريزومی
13تريزومي (Patau syndrome)18تريزومی (Edwards syndrome)
)Down syndrome( سندرم داون21تریزومی )Klinfelter syndrome-XXY(سندرم كالين فلتر
Triple X )Superfemale(مونوزمی
(Turner syndrome- XO)سندرم ترنر
Patau Syndrome1/20000
cleft-lip-baby
Edwards Syndrome1/5000
Maternal nondisjunction (95%)MosaismTranslocation
Down syndrome
• Monosomy• Nondisjunction in sperm
80%• Struc X• Nondisjunction in mitosis
(Mosaism)
ناهنجاري هاي ساختماني كروموزوم - 2••)Structural Chromosomal Anomalies(
• Isochromosome• Crossing over :
• Translocation21,13,14, 15 in Down syndrome
• Partial Deletion Cri du chat 5)microcephal, mental, cardiovas(
• Microdeletion Angelman 15 )speech, mental, movement( Prader- willi 15 )fatty, mental, hypogonad(
• Inversion
- ناهنجاري هاي حاصل از جهش ژنی 3•)Gene Mutation Anomalies(
• Marphan syndrome• Crigler-Najjar syndrome• Roberts syndrome• Alport syndrome• Aarskog-Scott syndrome• Savant syndrome• treacher-collins syndrome• Niemann–Pick disease• Cystic Fibrosis• DMD
Environmental factors
• Infectious Agents (& other disease)
• Drugs Agents (& Hormonic Agents)
• Chemical Agents• Physical Agents
• A( Viral infections• Rubella virus )German Measles( سرخجه ویروس
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% death
• Varicella-zoster virus)VZV( مرغان آبلهFirst 3 month-From Placenta- limb hypoplasia & parasis., hydrocephaly. Mental retardation, cataract
• HIV After 35th week- Systematic Chronic
infection)fangus,bacterial,viral,protozoan(
Infectious Agents
Infectious Agents• B( Nonviral infections
•Toxoplasma in each three munth -
death,microcephaly,hydroceohaly,cerebral calcification
•Treponema pallidum Syphilis, rhinitis,eye defect)cataract(,icterus,abnormal teeth,
splenohepatomegaly
نcاcهcنcجcاcرcی cاcب cطcبcتcرcم cیcرcدcاcم cیcاcه cیcرcاcمcیcب• Desease
•Diabetes Coudal disgenesis, death
•PKUmental retardation, microcephaly, cardiac defect
• Nutrient deficiency Iodine deficiency coused cretinism
• ObesityONTD, cardiac defect, …
• Hypoxy
Drugs AgentsCategory X drugs
Category D drugs
Category X drugs
Thalidomide Aminopterin methotrexate Busulfan Phenytoin Triazolam Warfarin
Isotretinoin
ClomiphenDiethylstilbestro
l Ethisterone Norethindrone Nicotine Alcohol
Category X drugs Thalidomide
antinauseant drug داروی ضد تهوعlimb defect (Amelia,Meromelia)Cardiac defectGIT atresyOptic & otic defect
Category X drugs Thalidomide
Category X drugsAminopterin MethotrexateBusulfan
Used in chemotererapy Dawerfism Myelomeningocele palate clef Growth retardation ophtalmic defect
Category X drugsAminopterin MethotrexateBusulfan
Used in chemotererapy Dawerfism Myelomeningocele palate clef Growth retardation ophtalmic defect
Category X drugsPhenytoin
Antileptic drug microcephalyGrowth & mental retardationpalate clefFinger & nail HypoplesiaSkull defect
Category X drugsWarfarin
Anti couagulant drug Mental retardation microcephaly optic n. atrophy Fetal bleeding
Category X drugsClomiphen
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
Category X drugsNicotine
Mental retardation Wheight loss Fetal Hypoxy Premature Parturition
Category X drugsAlcohol Fetal Alcholic Syndrome (FAS) Mental retardation microcephaly Cardivascular defect Limb & Face malformation Hairsutism
Category D drugs
Tetracycline
doxycycline
Streptomycin
Phenobarbital
Pentobarbital
Valsuroic acid
Diazepam
lorazepam
Lithium
Hydrochlorothiazid
e
Category D drugs
Phenobarbital & Pentobarbital
paliative drug Fetal malformation
Category D drugs
Diazepam, Lorazepam , Chlorodiazepoxide
antianxiety drug palate & lip clef specially in first 3 munth
Category D drugs
Lithium ,Phenothiazine
AntiedepressiveCardioVascular defect
Chemical Agents(heavy metals)
Organic mercury Blindness, deaf, cerebral pulsy (c.p)
Leadmental retardation, death of fetus
Poly chlorin biphenyil & Pentobarbital mental retardation, gingiva hyperplasia, exophthalmos, skull calcification, brown pigment in skin
Potassium iodideused as contrastment substance. mental retardation, goiter
Physical AgentsIonizing Radiation
Acute high dose (over 250 rads)
Microcephay,spina bifida,palate cleft, limb defect
Hyperthermiaanencephaly,spina bifida, mental retardation,
facial malformation, cardiac defect, limb defect
Male-mediated Teratogenesis Chromosomal defects & Mutation in germ cells
Environmental agent : transmission of paternal mediated toxicity through seminal fluid
Ultrasonography Maternal Serum Screening )AFP,hCG( AFP : Trisomy↓- NTD,GIT atresia,amniotic band↑
Amniocentesis Chorionic Villus Sampling )CVS(
Prenatal Diagnosis
Fetal Transfusion Fetal Medical Treatment Fetal Surgery Stem Cell Transplantation and Gene Therapy
Befor 18th week )activation of immune system(
Fetal Therapy
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