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 20-1) • 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 20-2) • 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 20-1) • 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 20-2) • XXX • XXY • XYY • Terasomy and pentasomy -XXXX, XXXXX, XXXY, XXYY, XXXYY, XXXXY • Triploidy or tetraploidy • Structural chromosome abnormalities

7. Down syndrome (table 20-1) 1. Incidence = 1:800 2. Chromosome 21 3. Incidence & maternal age (table 20-2)

8. Edwards syndrom (table 20-1) • Incidence = 1:8000 • Chromosome 18

9. Patau syndrom (table 20-1) • Incidence = 1:25000 • Chromosome 13

10. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 20-1) • 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 20-2) • XXX (female, 1:960) • XXY • XYY • Terasomy and pentasomy -XXXX, XXXXX, XXXY, XXYY, XXXYY, XXXXY • Triploidy or tetraploidy • Structural chromosome abnormalities

11. Turner syndrome (table 20-1) • Incidence =1:8000

12. Turner syndrome

13. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 20-1) • 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 20-2) • 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 20-3) • Male • Incidence 1:1080 • Small testes, hyalinization of seminiferous tubules (aspermatogenesis)

15. Anomalies caused by genetic factors: • Numerical chromosome abnormalities • Trisomy of autosomes (table 20-1) • Down syndrom (trisomy of chromosones 21) • Edwards syndrom (trisomy of chromosones 18) • Patau syndrom (trisomy of chromosones 13) • Trisomy of sex chromosomes (tabel 20-2) • 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 20-1) • Turner syndrom (trisomy of chromosones 21) • Edwards syndrom (trisomy of chromosones 18) • Patau syndrom (trisomy of chromosones 13) • Trisomy of sex chromosomes (tabel 20-2) • 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(侏儒症) (Fibroblast) 先天性成骨不全（玻璃娃娃） ALD腎上腺腦白質退化不良症 • X chromosome

22. Osteogenesis Imperferta先天性成骨不全 Pathogenic changes resulting in osteogenesis imperfecta can occur at any point of collagen synthesis. Beginning with transcription, followed by translation and subsequent posttranslational modification and transport. This figure outlines the basic processes involved in the molecular synthesis of collagen. 1, transcription (most common cause of OI is DNA mutation); 2, translation; 3, CRTAP-P3H1-CycB (CRTAP and P3H1 have recently been identified as causative mechanisms in OI. CRTAP, P3H1, and Cyclophylin B form a complex, which is responsible for the 3-OH of specific COL1 residues) other: prolyl-4-OH; 4, gal transferase/glc transferase; 5, assembly of procollagen chains; 6, disulfide bonds at N terminus; 7, triple helix assembly; 8, protein suicide (after spontaneous triple helix formation, the newly formed microfibril could undergo protein suicide and result in a milder clinical form of OI or the aberrant protein could be included in collagen fibril assembly, where the dominant negative effect results in more severe disease phenotype); 9, secretion; 10, N and C proteinase cleavage of propeptide; 11, collagen fibril assembly.

23. Anomalies caused by enviromental factors • Teratogens致畸原 (table 20-6) • Critical period of human development • Dosage of the drug or chemical • Genotype of the embryo

25. Critical period of human development

26. 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

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

28. Masculinized external genitalia外生殖器男性化 European Mole鼴鼠

29. Hydantoin syndrome內醯胺症候群 Anticonvulsants 抗痙攣藥 • Trimethadione • Phenytoin

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

31. Rubilla 德國麻疹

32. Toxoplasmosis 弓漿蟲

33. Body cavity, Mesenteries, and Diaphragm 陳建榮

34. E21 day Intraembryonic mesoderm Extraembryonic mesoderm

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

36. Embryonic folding

39. 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….

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

42. E33 day

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

44. Diaphragm formation

45. Diaphragm

46. E24 day E41 day E52 day

48. Cogenical diaphragmatic hernia先天性橫膈疝氣 Polyhydramnions羊水過多 Left-side defects

49. Eventration of diaphragm橫膈上升