Teratology
(birth defect)
Lecture Note
Teratology
Teratology is branch of embryology deals the
causes, mechanisms, and patterns of
abnormal development.
Developmental disorders present at birth are
called congenital anomalies, birth defect or
congenital malformation.
Congenital anomalies are of four clinically
significant types:
Malformation
Disruption
Deformation &
Dysplasia.
Types of Anomalies
Malformations
A morphologic defect of an organ, part of
an organ, or larger region of the body that
results from an intrinsically abnormal
developmental process.
Disruptions
A morphologic defect of an organ, part of
an organ, or a larger region of the body
that results from the extrinsic breakdown
of, or an interference with, an originally
normal developmental process.
Types of Anomalies…
Deformations
An abnormal form, shape, or position of a
part of the body that results from
mechanical forces .
Due to mechanical forces that mold a part of
fetus over a prolonged period of time
Clubfeet due to compression in the
amniotic cavity
Often involve the musculoskeletal
system & may be reversible
postnatally
Dysplasia
The presence of abnormal cell in the tissue
or organs
Principles of teratology
Susceptibility to teratogens depend on
genotype and its environmental interaction
Susceptibility varies with developmental
stage at time of exposure
Most sensitive period for inducing birth
defect is weeks 3-8 of gestation
Manifestations of abnormal development
depend on dose & duration of exposure
Teratogens act in specific ways on developing
cells & tissues to initiate abnormal
embryogenesis
Manifestations of abnormal development
death, malformation, growth retardation,
functional disorders.
Principles of teratology
Minor anomalies occur in approximately 15% of newborns.
These structural abnormalities, such as:
Microbial (small ears)
Pigmented spots &
Short palpebral fissures
These are not themselves detrimental to health but, in some
cases, are associated with major defects.
For example, infants with:
One minor anomaly have a 3% chance of having a major
malformation;
Those with two minor anomalies have a 10% chance; and
Those with three or more minor anomalies have a 20%
chance.
Therefore, minor anomalies serve as clues for diagnosing more serious
underlying defects.
Birth Defect (Congenital Malformations)
Causes
Genetic/chromosomal
Enviornmental
Multifactorial
Incidence/epidemology/
2-3% of newborn (4-6% by
age 5)
In 40-60% of all birth defects
cause is unknown
Genetic/chromosomal
(10%-15%)
Environmental (7-10%)
Multifactorial (genetic &
environmental) (20%-
25%)
Genetic factors for birth defect
Most Common Aneuploidy
Numerical Abnormalities
Trisomy 13 (Patau syndrome)
Trisomy 18 (Edwards syndrome)
Trisomy 21 (Down syndrome) 18
Klinefelter syndrome (47,XXY)
21
Monosomy (45,X; Turner
syndrome) Triple X Syndrome
Structural Abnormalities 13
Mutant Genes
Down syndrome (trisomy 21)
Extra copy of Chromosome 21
Growth retardation
Varying degrees of mental
retardation
Craniofacial abnormalities
Upward slanting eyes
Epicanthal folds
Flattened facies
Small ears
Cardiac defects
Hypotonia
Most of the time due to meiotic
nondisjunction
risk in women > 35 (1 in 1000 1 in 400)
Trisomy 18 (Edwards syndrome )
Mental retardation
Congenital heart defects
Low set ears
Flexion of fingers & hands
Micrognathia
Renal anomalies
Infants usually die by age 2
months
Incidence is 1 in 5000
Trisomy 13 (Patau syndrome)
Mental retardation
Congenital heart defects
Deafness
polydactyly (extra digits).
A small omphalocele (herniation of
viscera into umbilical cord)
Cleft lip & palate
Eye defects (Microphthalmia,
Anophthalmia, Coloboma
Most infants die by age 3 months
Incidence 1 in 15,000
Klinefelter Syndrome (47, XXY)
Found only in males
Usually detected at puberty
1 in 500 males
Nondisjunction f XX homologues
Sterility
Testicular atrophy
Hyalinization of seminiferous
tubules
Gynecomastia
Maybe some mental
impairment
with # of X chromosomes
(e.g. 48, XXXY)
Turner Syndrome
Usually (45, X) missing one X
chromosome
Found in women with unmistakably
female appearance
Absence of ovaries (gonadal
dysgenesis)
Short stature
Webbed neck (frequently)
Lymphedema of the extremities
Skeletal deformities
Broad chest with widely spaced
nipples
Structural Abnormalities
May involve one or more
chromosomes
Usually result from chromosome
breakage followed by
reconstitution in an abnormal
combination.
Chromosome breakage may be
induced by various
environmental factors, for
example, radiation, drugs,
chemicals, and viruses.
Broken piece may be lost
Partial deletion of chromosome 5
Cri-du-chat (cry of the cat)
syndrom
a weak catlike cry
Microcephaly
Mental retardation
Congenital heart disease
Mutant Genes
• Many congenital malformations
are inherited
Some show a clear mendelian
pattern of inheritance
In many cases abnormality is
attributed to a change in the
structure or function of a single
gene. “single gene mutation”
Estimated that this type of
defect makes up about 8% of
all human malformations
Mutant Genes
A boy with achondroplasia
Results from a g-to-a
transition
Short stature,
Short limbs and fingers
Normal length of trunk
Bowed legs
A relatively large head
Prominent forehead, &
Depressed nasal bridge
2.Environmental factors
Environmental factors
cause 7% to 10% of
congenital anomalies
Infectious agents
Radiation
Chemical Agents/Drugs
Hormones
Maternal Disease
Nutritional Deficiencies
Hypoxia
Infectious Agents
Rubella (German Measles)
Malformations of the eye (6th
week)
• Cataract
• Microphthalmia
Malformations of the ear (9th
week)
• Congenital deafness due to
destruction of cochlea
Malformations of the heart
(5th -10th week)
• Patent ductus arteriosis
• Atrial septal defects
• Ventricular septal defects
Infectious Agents contt…
Rubella (German measles)
May be responsible for some
brain abnormalities
• Mental retardation
Intrauterine growth
retardation
Virus infects fetus via the
placenta
• Infection of the child may
persist after birth for a
number of years
• Infection can be transmitted
to hospital personnel
Vaccines are considered safe &
effective
Infectious Agents contt
Cytomegalovirus
Disease is often fatal early on
Malformations - Microcephaly
Cerebral calcifications
Blindness - Chorioretinitis
Kernicterus (a form of jaundice)
multiple petechiae of skin
Hepatosplenomegaly
Mother asymptomatic
Infectious Agents contt
Herpes (simplex Virus)
Intrauterine infection of fetus
occasionally occurs
Usually infection is transmitted
close to time of delivery
Abnormalities (rare)
• Microcephaly
• Microphthalmos
• Retinal dysplasia
• Hepatosplenomegaly
• Mental retardation
Usually child infected by mother
at birth
• Inflammatory reactions
during first few weeks
Infectious Agents contt
Varicella (chickenpox)
Congenital anomalies
• 20% incidence following
infection in 1st trimester
• Limb hypoplasia
• Mental retardation
• Muscle atrophy
HIV/AIDS
Microcephaly
Growth retardation
Abnormal facies (expression or
appearance of the face)
Infectious Agents contt
Toxoplamosis
• Protozoa parasite (Toxoplama gondii)
• causing destructive changes in the brain
(intracranial calcifications) and eyes
(chorioretinitis) that result in
Mental deficiency
Microcephaly
Microphthalmia &
Hydrocephaly
Syphilis
– Congenital deafness
– Mental retardation
– Diffuse fibrosis of organs (eg. liver &
lungs)
Infectious Agents contt
Radiation
Teratogenic effect of ionizing
radiation well established
Microcephaly
Skull defects
Spina bifida
Blindness
cleft palate
Extremity defects
Direct effects on fetus or indirect
effects on germ cells
May affect succeeding generations
Avoid X-raying pregnant women
Infectious Agents contt
Drugs
Thalidomide
Antinauseant & sleeping pill
Found to cause amelia &
meromelia
Total or partial absence of
the extremities
Intestinal atresia
Cardiac abnormalities
Infectious Agents contt
Drugs (cont.) Anticonvulsants (to treat
Aminopterin epilepsy)
Antagonist of Folic Acid Antipsychotic drugs (major
Antineoplastic agent which tranquilizers)
inhibits mitosis Antianxiety drugs (minor
Defects tranquilizers)
Anticoagulants
• Anencephaly
Antihypertensive agents
• Meningocele
• Hydrocephalus
• Cleft lip & palate
Alcohol
Fetal alcohol syndrome
Craniofacial abnormalities
Limb deformities
Cardiovascular defects
Mental retardation
Growth deficiency
Indistinct philtrum,
Thin upper lip,
Depressed nasal bridge,
Short nose, and
Flat midface.
Cigarette Smoking
Has not been linked to major
birth defects
Smoking does contribute to
intrauterine growth
retardation & premature
delivery
Some evidence that causes
behavioral disturbances
Hormones
Androgenic Agents
Synthetic progestins were used
frequently to prevent abortion
Ethisterone & norethisterone
Have considerable
androgenic activity
Masculinization of female
genitalia
Hormones
Diethylstilbesterol(
Commonly used in prevent abortion; in
DES caused increased incidence of
vaginal & cervical cancer in women who
had been exposed to DES in utero
In addition high % suffered from
reproductive dysfunction
Oral Contraceptives
Low teratogenic potential, discontinue if
pregnancy suspected
Maternal Disease
Disturbances in CHO metabolism
(diabetic mothers)
High incidence of stillbirth,
neonatal deaths
Abnormally large infants
Congenital malformations:
risk 3-4X
Cardiac, Skeletal, CNS
Anomalies
Caudal dysgensis
Partial or complete
agenesis of sacral
vertebrae in conjuction
with hindlimb
hypoplasia
Environmental Chemicals
Mercury
– Fish, seed corn sprayed with
mercury containing fungicide
• Multiple neurological symptoms
Lead
– abortions
– Growth retardation
– Neurological disorders
Prevention of birth defects
Good prenatal care/ follow up /
Iodine supplementation
eliminates mental retardation &
bone deformities
Folate/Folic Acid supplementation
incidence of neural tube
defects
Avoidance of alcohol & other
drugs during all stages of
pregnancy
incidence of birth defects
END
