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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 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%
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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 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%
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 = 1:800 2. Chromosome 21 3. Incidence & maternal age (table 8-2)
Edwards syndrom (table8-1) • Incidence = 1:8000 • Chromosome 18
Patau syndrom (table8-1) • Incidence = 1:25000 • 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) • Incidence =1:8000
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) • Male • Incidence 1:1080 • 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
Structural chromosome abnormalities: • Translocation移位 • Deletion削除 • Duplications複製 • Inversion反轉 • Isochromosomes同染色體
Structural chromosome abnormalities Terminal deletion Reciprocal translocation Ring chromosome Paracentric inversion Duplication Robertsonian translocation Isochromosome
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
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
Hydantoin syndrome • Anticonvulsants 抗痙攣藥 • Trimethadione • Phenytoin
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……..
E21 day Intraembryonic mesoderm Extraembryonic mesoderm
胸壁、腹壁 Dorsal mesentery 背側腸系膜 • Dorsal mesentery: • Intraembryonic mesoderm • Extraembryonic mesoderm
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 心包腹膜管 橫中膈 • Embryonic cavities: • Pleura cavity • Pericardial cavity • Peritoneal cavity
Pleura and pericardial cavities formation 胸膜心包褶 胸膜心包膜 纖維性心包膜
E24 day E41 day E52 day
Cogenical diaphragmatic hernia先天性橫膈疝氣 Polyhydramnions Left-side defects