Human Birth Defects

陳建榮

http://web.nchu.edu.tw/pweb/index2.php?pid=75

Cogenital anomaly 先天性畸形Teratology 畸胎學

Cause of human congenital anomaliesChromosome 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%

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

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

Down syndrome (table8-1)1. Incidence = 1:8002. Chromosome 213. Incidence & maternal age (table 8-2)

Edwards syndrom (table8-1)1. Incidence = 1:80002. Chromosome 18

Patau syndrom (table8-1)1. Incidence = 1:250002. Chromosome 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-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

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

Turner syndrome

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

Klinefelter syndrom (XXY) (table 8-3)1. Male 2. Incidence 1:10803. Small testes, hyalinization of seminiferous tubules (aspermatogenesis)

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

Triploidy

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

Structural chromosome abnormalities

Reciprocal translocationTerminal deletion

Ring chromosome

Duplication

Isochromosome

Paracentric inversion

Robertsonian translocation

Cri du chat syndrome 貓叫症候群

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

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

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

Critical period of human development

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

Fetal alcohol syndrome (FAS) 胎兒酒精症侯群

Masculinized external genitalia 外生殖器男性化

Anticonvulsants 抗痙攣藥-Trimethadione-Phenytoin

Hydantoin syndrome

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…… ..

Rubilla 德國麻疹

Toxoplasmosis 弓漿蟲

Body cavity, Mesenteries, and

Diaphragm陳建榮

Intraembryonic mesodermExtraembryonic mesoderm

E21 day

胸壁、腹壁

Dorsal mesentery背側腸系膜

Dorsal mesentery:-Intraembryonic mesoderm-Extraembryonic mesoderm

Embryonic folding

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….

Division of embryonic body cavity

Embryonic cavities:-Pleura cavity-Pericardial cavity-Peritoneal cavity

心包腹膜管

橫中膈

E33 day

Pleura and pericardial cavities formation

胸膜心包褶

胸膜心包膜

纖維性心包膜

Diaphragm formation

Diaphragm

E24 day E41 day E52 day

Cogenical diaphragmatic hernia 先天性橫膈疝氣

PolyhydramnionsLeft-side defects

Eventration of diaphragm 橫膈上升