Human Birth Defects

1. Human Birth Defects 陳建榮 http://web.nchu.edu.tw/pweb/index2.php?pid=75

2. Cogenital anomaly先天性畸形 Teratology 畸胎學

3. Cause of human congenital anomalies Chromosome染色体異常 7% – 8% Gene基因突變 6%– 7% Multifactorial inheritance多重因子遺傳 7% –10% Environmental agents環境因素 20%–25% Unknown未知病因 50%–60%

4. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 8-1) • Down syndrom (trisomy of chromosones 21) • Edwards syndrom (trisomy of chromosones 18) • Patau syndrom (trisomy of chromosones 13) • Monosomy X chromosome • Trisomy of sex chromosomes (tabel 8-2) • XXX • XXY • XYY • Terasomy and pentasomy • -XXXX, XXXXX, XXXY, XXYY, XXXYY, XXXXY • Triploidy or tetraploidy • Structural chromosome abnormalities

6. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 8-1) • Down syndrom (trisomy of chromosones 21) • Edwards syndrom (trisomy of chromosones 18) • Patau syndrom (trisomy of chromosones 13) • Monosomy X chromosome • Trisomy of sex chromosomes (tabel 8-2) • XXX • XXY • XYY • Terasomy and pentasomy • -XXXX, XXXXX, XXXY, XXYY, XXXYY, XXXXY • Triploidy or tetraploidy • Structural chromosome abnormalities

7. Down syndrome (table8-1) 1. Incidence = 1:800 2. Chromosome 21 3. Incidence & maternal age (table 8-2)

8. Edwards syndrom (table8-1) • Incidence = 1:8000 • Chromosome 18

9. Patau syndrom (table8-1) • Incidence = 1:25000 • Chromosome 13

10. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 8-1) • Down syndrom (trisomy of chromosones 21) • Edwards syndrom (trisomy of chromosones 18) • Patau syndrom (trisomy of chromosones 13) • Monosomy X chromosome • Turner syndrome (X,45) • Trisomy of sex chromosomes (tabel 8-2) • XXX (female, 1:960) • XXY • XYY • Terasomy and pentasomy • -XXXX, XXXXX, XXXY, XXYY, XXXYY, XXXXY • Triploidy or tetraploidy • Structural chromosome abnormalities

11. Turner syndrome (table8-1) • Incidence =1:8000

12. Turner syndrome

13. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 8-1) • Down syndrom (trisomy of chromosones 21) • Edwards syndrom (trisomy of chromosones 18) • Patau syndrom (trisomy of chromosones 13) • Monosomy X chromosome • Trisomy of sex chromosomes (tabel 8-2) • XXX (female, 1:960) • XXY • XYY • Terasomy and pentasomy • -XXXX, XXXXX, XXXY, XXYY, XXXYY, XXXXY • Triploidy or tetraploidy • Structural chromosome abnormalities

14. Klinefelter syndrom (XXY) (table 8-3) • Male • Incidence 1:1080 • Small testes, hyalinization of seminiferous tubules (aspermatogenesis)

15. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 8-1) • Down syndrom (trisomy of chromosones 21) • Edwards syndrom (trisomy of chromosones 18) • Patau syndrom (trisomy of chromosones 13) • Trisomy of sex chromosomes (tabel 8-2) • XXX (female, 1:960) • XXY • XYY • Terasomy and pentasomy • -XXXX, XXXXX, XXXY, XXYY, XXXYY, XXXXY • Triploidy or tetraploidy • Structural chromosome abnormalities

16. Triploidy

17. Structural chromosome abnormalities: • Translocation移位 • Deletion削除 • Duplications複製 • Inversion反轉 • Isochromosomes同染色體

18. Structural chromosome abnormalities Terminal deletion Reciprocal translocation Ring chromosome Paracentric inversion Duplication Robertsonian translocation Isochromosome

19. Cri du chat syndrome貓叫症候群

20. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 8-1) • Turner syndrom (trisomy of chromosones 21) • Edwards syndrom (trisomy of chromosones 18) • Patau syndrom (trisomy of chromosones 13) • Trisomy of sex chromosomes (tabel 8-2) • XXX (female, 1:960) • XXY • XYY • Terasomy and pentasomy • -XXXX, XXXXX, XXXY, XXYY, XXXYY, XXXXY • Triploidy or tetraploidy • Structural chromosome abnormalities • Mutant genes

21. Achondroplasia軟骨發育不全 (Fibroblast) • 先天性成骨不全 • ALD腎上腺腦白質退化不良症 • X chromosome

22. Anomalies caused by enviromental factors • Teratogens致畸原 (table 8-6) • Critical period of human development • Dosage of the drug or chemical • Genotype of the embryo

24. Critical period of human development

25. Environmental factors • Drugs • Alcohol • Isotretinoin (13-cis-retinoic acid) • Lithium • Phenytoin • Thalidomide • Warfarin • Chemicals • Methylmercury (Minamata bay disease) • PCB (polychlorinated biphenyls) • Infection • CMV, HSV, HIV, Parvovirus B19, Rubella, Varicella, Toxoplasmosis, Syphilis • Radiation (vs Electromagnetic field, Ultrasound) • * > 25000 millirads: harmful to CNS • * diagnostic level: no conclusive proof • chest 1 millirad • pelvis 0.3 – 2 rad • * upper limit of maternal exposure 500 millirad • * embryo exposure < 5rad: minuscule • Maternal factor • DM, PKU • Mechanical factors

26. Fetal alcohol syndrome (FAS) 胎兒酒精症侯群

27. Masculinized external genitalia外生殖器男性化

28. Hydantoin syndrome • Anticonvulsants 抗痙攣藥 • Trimethadione • Phenytoin

29. Tranquilizers 鎭靜劑 • Thalidomide 抗生素 抗凝血劑 止吐藥 抗腫瘤藥 皮質類固醇 鉀鹽……..

30. Rubilla 德國麻疹

31. Toxoplasmosis 弓漿蟲

32. Body cavity, Mesenteries, and Diaphragm 陳建榮

33. E21 day Intraembryonic mesoderm Extraembryonic mesoderm

34. 胸壁、腹壁 Dorsal mesentery 背側腸系膜 • Dorsal mesentery: • Intraembryonic mesoderm • Extraembryonic mesoderm

35. Embryonic folding

38. Mesenteries: • Derived from intra- and extra-embryonic mesoderm • -Dorsal mesentery • -Foregut, midgut, hindgut • -greater omentum, mesentery, mesocolon… • Ventral mesentery • Foregut • Lessor omentum, falciform lig., coronary lig….

39. Division of embryonic body cavity 心包腹膜管 橫中膈 • Embryonic cavities: • Pleura cavity • Pericardial cavity • Peritoneal cavity

41. E33 day

42. Pleura and pericardial cavities formation 胸膜心包褶 胸膜心包膜 纖維性心包膜

43. Diaphragm formation

44. Diaphragm

45. E24 day E41 day E52 day

47. Cogenical diaphragmatic hernia先天性橫膈疝氣 Polyhydramnions Left-side defects

48. Eventration of diaphragm橫膈上升