1. Congenital Anomalies and Teratogens Jun Zhou （周俊） School of Medicine, ZheJiang University 20140106

2. Birth defect, congenital malformation and congenital anomaly Are synonymous terms used to describe structural, behavioral, functional and metabolic disorders present at birth

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

4. Genetic Causes Molecules that regulate development Enzymes Structural genes Localized to a Chromosome – gene unknown

5. Environmental factors (Teratogens) Infectious agents-virus Physical agents X-rays, Hyperthemia, etc Chemicals agents alcohol, Cocaine, etc Hormones Maternal diabetes

6. 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

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

8. Ultrasound/Amnniocentesis

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

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

11. Fluorescent In Situ Hybridization

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

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

15. Human fetal specimens

16. uterus

17. Fetus, amnion and uterus

18. Normal fetus. How old is it?

19. Growth in Length and Weight During the Fetal Period Age(weeks)CRL(cm) Crown-rump length Weight(g) 9-12 13-16 17-20 21-24 25-28 29-32 33-36 37-38 5-8 9-14 15-19 20-23 24-27 28-30 31-34 35-36 10-45 60-200 250-450 500-820 900-1300 1400-2100 2200-2900 3000-3400

22. Chorion and fetus, amnion

23. Chorion and fetus

24. Placenta with two umbilical cord

25. Placenta with three umbilical cord

29. Conjoined twins

31. Teratoma

32. Anencephaly

33. Anencephaly with following meningomyeloecel

34. meningomyeloecel

35. Malformation of head

37. Horse shoe- kidney

40. Umbilical cord encircles the neck

41. A cyst near the ear

42. THE END!