![Page 1: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/1.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Human Birth Defect
Qian Xiaojing
Dept. of Anatomy, Histology &
Embryology
PUMC
Tel:69156461
E-mail : [email protected]
![Page 2: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/2.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
![Page 3: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/3.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Introduction
Causes of birth defects
Genetic factors
Environmental factors
Multifactorial inheritance
Diagnosis & treatment
Content
![Page 4: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/4.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
I. Introduction
1.Birth defect (congenital
malformation / anomaly)
2. Teratology (dysmorphology)
“Study of monster”
Study the causes, mechanisms, and
patterns of abnormal development.
Developmental disorders present
at birth.
structural, functional, metabolic,
behavioral, or hereditary
disorders.
![Page 5: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/5.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
3. Types of birth defects
not all variations of development are anomalies
malformation
畸形
disruption
破坏
deformation
变形
dysplasia
发育不良 • intrinsic
•abnormal from
the beginning
(primordium)
•extrinsic
breakdown
•not inherited
mechanical
forces dyshistogenesis
![Page 6: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/6.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
4. Incidence of birth defect
• infant mortality ~20%
• major anomalies ~5%
• minor anomalies ~15%
multiple minor defects
↓
1/ more major defects
![Page 7: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/7.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
![Page 8: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/8.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
II. Causes of Birth Defects
1. Genetic factors
2. Environmental factors
3. Multifactorial inheritance
![Page 9: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/9.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
1. Genetic factors 1/3
• Numerical abnormalities of chromosomes
• Structural abnormalities of chromosomes
• Mutations of genes
![Page 10: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/10.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
1) Numerical abnormalities of chromosomes
aneuploidy (非整倍体)
monoploidy
diploidy
(46.XY)
polyploidy (多倍体)
monosomy 单体
trisomy 三体
单倍体
hypodiploidy 亚二倍体
hyperdiploidy 超二倍体
triploidy 三倍体
tetraploidy 四倍体
tetrasomy
四体
euploidy (整倍体)
![Page 11: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/11.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
(1) Polyploidy
triploidy
tetraploidy
![Page 12: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/12.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• triploidy (69, 3n)
intrauterine growth retardation
head-body disproportion
![Page 13: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/13.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Nondisjunction
(2) Aneuploid 非整倍体
![Page 14: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/14.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
(2) Aneuploidy
Autosomes Sex
chromosomes
Monosomy lethal 1%
Trisomy √
√
![Page 15: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/15.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
a. hypodiploid of sex chromosomes
Turner syndrome (45, X)
• short stature
• webbed neck
• defective gonadal development
• absence of sexual maturation
• mental retardation
• lymphedema
Mosiacism (45, X / 46, XX)
亚二倍体
![Page 16: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/16.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
cystic hygroma (囊状水囊瘤)lymphangioma(淋巴管瘤 ) lymphedema
Turner syndrome
![Page 17: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/17.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
b. hyperdiploid of sex chromosomes
XYY
![Page 18: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/18.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Klinefelter’s syndrome
• testicular atrophy
• sterility
• gynecomastia (男子女性型乳房)
(47, XXY; 48, XXXY; 49, XXXXY)
![Page 19: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/19.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
mental deficiency
heart defects
c. Trisomy of autosomes
![Page 20: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/20.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Trisomy 21 (Down syndrome)
John Langdon Down, 1866
![Page 21: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/21.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• special face
flat nasal bridge
protruding tongue
upward slant to palpebral fissures
• mental retardation
• short stature
• heart defect
• transverse palmar flexion
crease
Trisomy 21 (Down syndrome)
贯通掌
睑裂上斜
![Page 22: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/22.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Down’s syndrome & Alzheimer Disease
• Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by
modulating glutamate receptor recycling in Down's syndrome. Nat Med, 2013.
19(4): p. 473-80.
• Sorting nexin 27 regulates Abeta production through modulating gamma-secretase
activity. Cell Rep, 2014. 9(3): p. 1023-33.
![Page 23: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/23.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
2) Structural abnormalities of chromosomes
• Deletion
• Inversion
• Translocation
• Duplication
• Ring chromosome
• Isochromosome
![Page 24: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/24.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• microcephaly
• mental retardation
• developmental delay
• behavioral problems
• speech & communication
problems
• congenital heart disease
Cri du chat syndrome
5p- → catlike cry
“cry of the cat” in French
• deletion
![Page 25: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/25.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Angelman syndrome
(happy puppet syndrome)
maternal 15q12-
• severe mental retardation
• microcephaly
• brachycephaly 短头
• ataxic movement运动失调
• excessive laughter
Prader-Willi syndrome
paternal 15q12-
• mild mental retardation
• obesity
• hyperphagia (摄食过量)
• hypogonadism PWS AS
genetic imprinting • microdeletion
![Page 26: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/26.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
1. Genetic factors
• Numerical abnormalities of chromosomes
• Structural abnormalities of chromosomes
• Mutations of genes
![Page 27: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/27.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Phenylketonuria (PKU)
3) Mutations of genes
苯丙酮尿症
mental retardation
absent of pigments
phenylalanine hydroxylase deficiency
![Page 28: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/28.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Achondroplasia 软骨发育不全
• short stature
• short limbs & fingers
• prominent forehead
nt1138 G>A or G>C Fibroblast growth factor receptor 3 (FGFR3)
![Page 29: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/29.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
II. Causes of birth defects
1. Genetic factors
2. Environmental factors
3. Multifactorial inheritance
![Page 30: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/30.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
1) Teratogens
1941, N. Gregg, rubella virus, cataracts, cardiac defects, deafness
1961, W.Lenz , thalidomide, a sedative, severe limb defect
(白内障) (风疹病毒)
(酞胺哌啶酮)
Worldwide attention on the role of drugs & viruses
as cause of human birth defects
![Page 31: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/31.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• Radiation
• Mechanical factors
• Environmental chemicals
• Infectious agents
• Maternal factors
• Drugs
1) Teratogens
A teratogen is any agent that can produce a congenital
anomaly or raise the incidence of an anomaly in the
population.
![Page 32: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/32.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
atomic explosion over Japan
Survived pregnant women:
28% aborted;
25% died <1 year;
25% severe birth defect (CNS)
•ultrasonic waves
(1) Radiation
• acute high does
• diagnostic radiation
cell death, chromosome injury,
mental deficiency,
deficient physical growth
no confirmed harmful effects
![Page 33: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/33.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• Oligohydramnios
• Amniotic bands
(2) Mechanical factors
Congenital hip dislocation先天性髋关节脱位 clubfoot马蹄内翻足
![Page 34: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/34.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• organic mercury
Minamata disease (水俣病)
neurologic & behavioral disturbance
(3) Environmental Chemicals
• lead, polychlorinated biphenyls… (聚氯联二苯)
![Page 35: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/35.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• Fukishima meltdown Mar 11, 2011
congenital hypothyroidism in 5 US states
increased by 16%, compared to 2010
福岛
![Page 36: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/36.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
(4) Infectious agents
• T: Toxoplasma Gondii (TG)
• O: other (syphilis)
• R: Rubella virus
• C: Cytomegalovirus (CMV)
• H: Herpes simple virus (HSV)
TORCH infections
cause similar clinical &
pathological manifestations
弓形虫
![Page 37: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/37.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
fetal death
classic triad of symptoms
• diffused intracranial calcification
• chorioretinitis
• hydrocephaly
• Toxoplasma Gondii, TG
intracellular parasite
intracranial calcification chorioretinitis
弓形虫
脉络膜视网膜炎
脑积水
transplacental
![Page 38: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/38.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
4-5w
Congenital rubella
syndrome (CRS)
cataract
deafness
cardiac defects
德国麻疹
• Rubella
German measles
风疹
![Page 39: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/39.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• spontaneous abortion
• Infection later in pregnancy
may result in severe birth
defects
IUGR
deafness
eye defects
microcephaly ( 小头)
cerebral palsy (脑瘫)
hepatosplenomegaly
• Cytomegalovirus (CMV)
most common viral infection of fetus
1%
肝脾肿大
![Page 40: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/40.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
cutaneous lesion
• Herpes simplex virus (HSV) 单纯疱疹病毒
abortion,
prematurity
most often during
delivery
Skin, eyes, mouth (SEM)
*CNS disease
• Varicella
skin scarring
muscle atrophy,
hypoplasia of limbs
eye and brain damage
mental deficiency
Highly infectious
![Page 41: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/41.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
tetracycline
bones & teeth
Antibiotics:
四环素 链霉素
Penicillin widely used during pregnancy for >30yrs
Streptomycin
deafness
![Page 42: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/42.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
deafness,abnormal teeth & bones, mantel deficiency, facial defects
• Treponema pallidum 梅毒螺旋体
• Human immunodeficiency virus (HIV)
delivery
breast-feeding
![Page 43: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/43.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• nutritional deficiencies
1st trimester hypertension & strokes
2ed trimester heart disease & diabetes
3rd trimester blood clotting defects
The embryonic origin of adult-onset illnesses
Barker hypothesis
David Barker
(5) Maternal factors
![Page 44: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/44.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• Diabetes
spontaneous miscarriage
birth defect
• macrosomia (巨大儿)
• sirenomelia (并肢)
• brain abnormalies
• skeletal defects
• congenital heart defects
(5) Maternal factors
• Thyroid disease • cretinism
• goiter
• phenylketonuria
• brain damage
• mental deficiency cretinism
(呆小症)
sirenomelia
![Page 45: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/45.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
FDA Pregnancy Categories
• The FDA has established five categories to indicate the potential of a drug to
cause birth defects if used during pregnancy.
• Category A: failed to demonstrate a risk to the fetus
• Category B: Animal studies: failed to demonstrate a risk to the fetus
no adequate & well-controlled studies in pregnant women.
• Category C: Animal studies: an adverse effect on the fetus
no adequate and well-controlled studies in humans
• Category D: positive evidence of human fetal risk,
potential benefits may warrant use of the drug in pregnant
women despite potential risks
• Category X: studies in animals or humans have demonstrated fetal abnormalities
use of the drug in pregnant women clearly outweigh potential benefits
(6) Drugs
absolute contraindication in pregnancy
![Page 46: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/46.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Tranquilizers (镇静剂): thalidomide
Antibiotics: tetracycline, streptomycin derivatives
Analgesic : (镇痛药): aspirin, acetaminophen ( 对乙酰氨基酚,扑热息痛)
Hormone: androgens, progestogens, diethylstilbestrol (DES),
Antineoplastic agents (抗肿瘤药): aminopterin (氨基蝶呤)
Retinoic acid: isotretinoin (异维甲酸)
Antihypertensive agent: inhibit angiotensin converting enzyme (ACEI)
Insulin & hypoglycemic drugs(降糖药 )
Thyroid drugs: potassium iodide, radioactive iodine
Anticoagulants (抗凝剂): warfarin (华法林)
Anticonvulsants (抗癫痫药): trimethadione (三甲双酮), phenytoin (苯妥英), valproic
acid (丙戊酸)
Psychotroic drug(治疗精神疾病药物): lithium, benzodiazepine derivatives (苯并二氮卓类 )
Social drugs: Cigarette smoking, Alcohol
Illicit drugs (违禁药): marijuana (大麻) , cocaine, methadone (美沙酮)
(6) Drugs
![Page 47: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/47.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• meromelia(部分缺肢畸形)
phocomelia, amelia, micrmelia
• hemangioma (血管瘤)
• absent of ears
phocomelia (短肢,海豹肢)
Thalidomide
amelia (无肢)
![Page 48: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/48.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
V ertebral
A nal
C ardiac
T rachea
E sophageal
R enal
L imb
己烯雌酚
Hormones
anal stenosis
• diethylstilbestrol (DES):
genital tract anomalies
• Oral contraceptive
![Page 49: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/49.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• aminopterin (氨基蝶呤)
• methotrexate (氨甲蝶呤)
folic acid antagonist
folate-binding protein
• intrauterine death
• CNS & skeletal defect
Antineoplastic agents
![Page 50: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/50.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Retinoic acid 视黄酸,维甲酸
a metabolite of vitamin A
• craniofacial dysmorphism
• micortia
• micrognathia
• cleft palate
• thymic aplasia
• cardiovascular defects
• neural tube defects
Isotretinoin 异维甲酸
Dosage of vitamin A
小耳
小颌
![Page 51: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/51.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Cigarette
nicotine causes hypoxia
• intrauterine growth retardation (IUGR)
• premature delivery
• low birth weight
![Page 52: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/52.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Alcohol: fetal alcohol syndrome (FAS)
• mental deficiency
• special face
•smooth philium
• thin upper lip
(人中)
![Page 53: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/53.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
2) Principles in teratogenesis
Critical periods of development
Dosage of the drug or chemical
Genotype ( genetic constitution) of the embryo
![Page 54: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/54.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
(1) Highly sensitive period
3rd-8th w, embryonic period, organogenetic period
Tissue & organ are forming
cell division, differentiation, and morphogenesis are at their peak
![Page 55: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/55.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
(2) Different organs have different susceptible period
corresponding to their own critical development stage.
![Page 56: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/56.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
《中国出生缺陷防治报告(2012)》
![Page 57: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/57.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
(3) Different teratogens also have different susceptible
period.
• Rubella virus
1st mon. 50%; 2nd mon. 22%; 3rd month 7%.
![Page 58: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/58.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• Thalidomide
Critical period for limb development: 24-36day
![Page 59: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/59.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
3. Multifactorial inheritance
combination of genetic & environmental factors
![Page 60: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/60.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
III. Diagnosis & treatment
1.Education
• Away from deleterious factors
• Folate supplementation
2. Prenatal Diagnosis
3. Treatment
![Page 61: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/61.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
1) Noninvasive prenatal diagnosis
• Fetal monitoring
fetal heart rate monitoring
• Ultrasound
• Isolation of fetal cells in maternal blood
Trisomy 21
2. Prenatal Diagnosis
2) Invasive prenatal diagnosis
high-risk pregnancies
![Page 62: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/62.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
2) Invasive prenatal
diagnosis
• Amniocentesis
(15-18W, LNMP)
• Chorionic villi sampling (CVS)
(10-12W, LNMP)
• Fetoscopy
2. Prenatal Diagnosis
![Page 63: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/63.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
3. Treatment
• drugs
• surgery
![Page 64: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/64.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Summary
I. Introduction
II. Causes of birth defects
1.Genetic factors
a) Numerical abnormalities of chromosomes
b) Structural abnormalities of chromosomes
c) Mutations of genes
2.Environmental factors
3.Multifactorial inheritance
III. Diagnosis and treatment
summary
![Page 65: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/65.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
• Radiation
• Mechanical factors
• Environmental chemicals
• Infectious agents
• Maternal factors
• Drugs
Teratogens
A teratogen is any agent that can produce a congenital
anomaly or raise the incidence of an anomaly in the
population.
summary
![Page 66: Human Birth Defectanatomy.sbm.pumc.edu.cn/mobile/files/pdf/Histology...protruding tongue upward slant to palpebral fissures •mental retardation •short stature •heart defect •transverse](https://reader033.vdocuments.net/reader033/viewer/2022041804/5e5312421c68b53f282ed655/html5/thumbnails/66.jpg)
PE
KIN
G U
NIO
N M
ED
ICA
L C
OL
LE
GE
Q
IAN
Highly sensitive period
3rd-8th w, embryonic period, organogenetic period
Tissue & organ are forming
cell division, differentiation, and morphogenesis are at their peak
summary