Congenital Anomalies and

Teratogens

Jun Zhou（周俊）School of Medicine, ZheJiang University20140106

Birth defect, congenital malformation and congenital anomaly

Are synonymous terms used to describe structural, behavioral, functional and metabolic disorders present at birth

Causes of Birth Defects

Genetic/Chromosomal - 15-20%

Environmental (teratogens) - 10-15%

Combined - 20-25%

Multiple Gestations - 1%

Unknown - 40-50%

Genetic Causes

Molecules that regulate development

Enzymes

Structural genes

Localized to a Chromosome – gene unknown

Environmental factors (Teratogens)

Infectious agents-virusPhysical agents

X-rays, Hyperthemia, etcChemicals agents

alcohol, Cocaine, etcHormonesMaternal diabetes

Periods of VulnerabilityPreembryonic period Pregerm (0-2 wks) Usually Death

Embryonic period Organogenesis (3-8 wks) Abnormalities of Form

(malformations)

Fetal period Growth/Maturation (9 wks – birth) Growth Retardation Mental dysfunction

Fetus vulnerable Rapid cell proliferationCell migrationCell differentiation

Current Methods of Diagnosis

UltraSound/Amniocentesis

Karyotyping Spectral Karyotyping

FISH - translocation/target

PCR of target sequence

RT-PCR - gene expression

Ultrasound/Amnniocentesis

Spectral Karyotyping

All 23 chromosome pairs at one time

Different Fluorescent probes

Useful for translocations

Fluorescent In Situ Hybridization

Chromosome mapping

Identify and localize discrete chromosomal abnomalities

Deletions

Fluorescent In Situ Hybridization

PCRUsing 2 small primers (20 bp)25-40 cycles of: Denature Anneal Synthesize

Identify gene expression or mutation

PCR

Using 2 small primers (20 bp)

25-40 cycles of: Denature Anneal Synthesize

Identify gene expression or mutation

Human fetal specimens

uterus

Fetus, amnion and uterus

Normal fetus. How old is it?

Growth in Length and Weight During the Fetal Period

Age(weeks) CRL(cm)

Crown-rump length

Weight(g)

9-12

13-16

17-20

21-24

25-28

29-32

33-36

37-38

5-8

9-14

15-19

20-23

24-27

28-30

31-34

35-36

10-45

60-200

250-450

500-820

900-1300

1400-2100

2200-2900

3000-3400

Chorion and fetus, amnion

Chorion and fetus

Placenta with two umbilical cord

Placenta with three umbilical cord

Conjoined twins

Teratoma

Anencephaly

Anencephaly with following meningomyeloecel

meningomyeloecel

Malformation of head

Malformation of head

Horse shoe-kidney

Umbilical cord encircles the neck

A cyst near the ear

THE END!