Congenital Anomalies and Teratogens Structural, behavioral, functional and metabolic disorders present at birth. The science that studies these disorders is teratology(畸形学). BD - 2-3% at birth (live), 4-6% by 1 yr ~20% of infant deaths

Causes of Birth Defects Genetic/Chromosomal - 15-20% Environmental (teratogens) - 10-15% Combined - 20-25% Multiple Gestations - 1% Unknown - 40-50%

1.Genetic/ Chromosomal Causes Down’s syndrome (21 trisomy) Turner’s syndrome(45,X) Microcephaly

2.Environmental causes Teratogens: agents that induce gross structural defects or “monsters”. Physical agents：X-rays、hyperthemia Chemical agents：heavy metals (mercury, lead), alcohol，Cocaine Infectious agents：virus, syphilis（梅毒） Drugs and Hormones

Factors that influence the extent of disruption by the toxic agent include: Exposure length Timing of exopure (what stage of development) Site targeted

Periods of Vulnerability Preembryonic period Pregerm (0-2 wks) Usually Death Embryonic period Organogenesis (3-8 wks) Abnormalities of Form (malformations) Fetal period Growth/Maturation (9 wks – birth) Growth Retardation Mental dysfunction Fetus vulnerable Rapid cell proliferation Cell migration Cell differentiation

Current Methods of Diagnosis UltraSound/Amniocentesis Karyotyping Spectral Karyotyping FISH - translocation/target PCR of target sequence RT-PCR - gene expression

Ultrasound/Amnniocentesis (羊膜穿刺)

Detection of Chorion

Spectral Karyotyping All 23 chromosome pairs at one time Different Fluorescent probes Useful for translocations

Fluorescent In Situ Hybridization Chromosome mapping Identify and localize discrete chromosomal abnomalities Deletions

Fluorescent In Situ Hybridization

PCR Using 2 small primers (20 bp) 25-40 cycles of: Denature Anneal Synthesize Identify gene expression or mutation