Outline 3.

Multifactorial inheritance- both

genetic and environmental factors
Classification of Birth Defects
Teratology: Study of Abnormal 50-60%- percentage of birth defects caused
Development
by unknown factor
Birth Defects Caused by Genetic
Factors Single minor defect- occurs approximately
Numeric Chromosomal Abnormalities  14% of the neonates ; has no serious
Structural Chromosomal Abnormalities medical significance; example: defects in
Birth Defects Caused by Mutant Genes external ear
Developmental Signaling Pathways  - may indicate presence of major defects
90%- percentage of infants having three or
Birth Defects Caused by Environmental
Factors more minor birth effects that may also have
Principles of Teratogenesis one or more major birth defects
Critical Periods of Human Development  Multiple major defects- found at 0.7% of
Human Teratogens infants; most infants die
Birth Defects Caused by Multifactorial Major developmental defects- more
Inheritance
common in young embryos but most of
Summary of Birth Defects
Clinically Oriented Problems 485 them abort spontaneously during the first
week
Chromosomal abnormalities- detect in 50-
60% of spontaneous abortion

International Classification of Diseases- most Causes of birth defects

widely used reference guide for classifying birth
defects

TERATOLOGY

Teratology- is the branch of embryology and

pathology concerned with the production,
developmental anatomy, and the classification
of malformed embryos and fetuses
Fundamental concept: some stages of
embryonic development is vulnerable to
disruption than others
7%-10% - percentage of birth effects accounted
to viruses, environmental toxins, and chemicals
Spina bifida cystica- a severe type of vertebral
defect in which part of the neural tube fails to
fuse
BIRTH DEFECTS CAUSED BY GENETIC FACTORS

Causes of birth effects

1. Genetic Factors- ex: chromosomal
abnormalities
2. Environmental Factors- ex: viruses,
drugs
Genetic factors- most important cause of
birth defects

Cleavage of zygotes less than 5 days- have

resulted to most of the abnormalities

Changes that occur in chromosome

complements
1. Numeric
2. Structural
- error in cell division in which there is
Numeric and Structural- changes may affect failure of a chromosomal pair or two
the sex chromosomes and autosomes chromatids of a chromosome to disjoin
during mitosis or meiosis
Chromosomal aberrations- caused individuals - will result to passing of chromosomal pair
to have phenotypes (morphologic or chromatids to one daughter cell and the
characteristics; example: physical characteristic other daughter cell to receive neither
of infants with down syndrome) - may occur during maternal or paternal
gametogenesis.
Genetic imbalance- cause the characteristic Turner syndrome – monosomy X
appearance chromosome abnormality; the paternal X
chromosome is usually missing; incidence in
Abnormal mechanisms initiated by genetic female neonates is estimated at 1 in 8000
factors may be identical to causal mechanisms live births; phenotype is female; secondary
initiated caused by teratogens sexual characteristics do not develop in
NUMERIC CHROMOSOMAL ABNORMALITIES 90%
of incidences

Trisomy of Autosomes- - three

chromosome
copies in a given pair; most common
abnormalities of chromosome number;
occurs with increasing frequency as
maternal
age increases
- meiotic nondisjunction of
chromosomes ; gamete with 24
instead of 23 chromosomes
- Trisomy 21 or Down Syndrome (most
common)
- Trisomy 18 or Edwards Syndrome
-Trisomy 13 or Patau Syndrome

Mosaicism – two or more cell types contain

Nondisjunction- cause of numeric aberrations
different numbers of chromosomes; leads
of
to
chromosomes
a less severe phenotype; IQ may almost be
normal
 Other descriptive terms used to describe
infants with multiple defects:

1. Polytopic field defect- it is a

pattern of defects derived from the
disturbance of a single developmental field
2. Sequence- s a pattern of multiple
defects derived from a single known or
presumed structural defect or mechanical
factor.
3. Syndrome- is pattern of multiple
defects thought to be pathogenetically
related and not known to represent a single
sequence or a polytopic field defect
4. Association- is a nonrandom
GLOSSARY OF TERATOLOGIC TERMS occurrence in two or more individuals of
multiple defects not known to be a
polytopic field defect, sequence, or
syndrome
5. Dysmorphology- is an area of
clinical genetics that is concerned with the
diagnosis and interpretation of patterns of
structural defects
Birth defect- structural abnormality of any
type, but not all variations of development are
defects or anomalies
- anatomical variations are common INACTIVATION GENES

● during embryogenesis; one of the two

Clinical significant types of birth defects X
1. Malformation- morphologic defect of chromosomes in female somatic cells is
an organ, part of an organ, or larger region of randomly activated and appears as a mass
the body that results from an intrinsically of sex chromatin
abnormal developmental process
2. Disruption- a morphologic defect of an ● clinical importance: each cell from a
organ, part of an organ, or a larger region of carrier of
the body that results from the extrinsic an X-linked disease has a mutant gene,
breakdown of or an interference with an causing the disease in either of the active or
originally normal developmental process inactive chromosomes
- cannot be inherited,
3. Deformation- n is an abnormal form, ANEUPLOIDY AND POLYPLOIDY
shape, or position of a part of the body that
results from mechanical forces. (ex: Aneuploidy- is any deviation from the
equinovarus foot or clubfoot) diploid
4. Dysplasia- a is an abnormal number of 46 chromosome
organization of cells in tissues and its - most common and clinically significant of
morphologic results. numeric chromosomal abnormalities
- is the process and the consequence of - common cause is nondisjunction
dyshistogenesis (abnormal tissue formation)
Aneuploid- is an individual who
has a chromosome number that is not an exact Tetraploidy- doubling of the diploid
multiple of the haploid number of 23 chromosome number from 46-92 probably
Polyploid - someone who has a chromosome occurs during the 1stcleavage division of
number multiple of haploid 23 other than the the zygote.
diploid number - tetraploid embryos abort very early, and
often
all than is recovered is an empty chorionic
sac (blighted embryo)

STRUCTURAL CHROMOSOMAL
ABNORMALITIES

Most
structural

Mosaicism- a condition in which two or more

cell types contain different numbers of
chromosomes (normal and abnormal).
- leads to a less severe phenotype, and the IQ
of the child may be almost normal (the defects
are usually milder than persons with trisomy or
monosomy).
- usually results from non-disjunction during chromosomal abnormalities result from
early cleavage of the zygote. chromosome breakage, followed by
-mosaicism from the loss of a chromosome by reconstitution in an abnormal combination
anaphase lagging is also possible. The
chromosome separate normally, but one of Chromosome breakage- may
them is delayed in its migration and is be induced by environmental factors such
eventually lost. as ionizing radiation, viral infections, drugs,
- The autosomes may be involved. and chemicals.

TRIPLOIDY AND TETRAPLOIDY Two aberrations of chromosome structure

Triploidy- most common type of polyploidy (69 that are likely to be transmitted from a
chromosomes) parent to an embryo (structural
- most frequently results from fertilization of rearrangement)
an oocyte by two sperms (dispermy). 1. Deletion- when a chromosome
- triploid fetuses have intrauterine growth breaks, part of it may be lost
retardation with severe head-body - Cri du chat syndrome: caused by partial
disproportion terminal deletion from the short arm of
chromosome 5; Affected infants have a
weak cat-like cry,microcephaly (small
neurocranium), severe mental deficiency, and DiGeorge Syndrome- thymic hypoplasia,
congenital heart disease.
- ring chromosome: is a type of
deletion chromosome from which
both ends have been lost, and the
broken ends have rejoined to form a
ring-shaped chromosome; are rare,
but they
have been found for all
chromosomes; found in Turner
syndrome and Edward syndrome

2. Translocation- is the transfer

of a piece of one chromosome to a parathyroid hypoplasia, contruncal and
nonhomologous chromosome. - cardiac defects, facial dysmorphism
-does not necessarily cause abnormal
development.
- reciprocal translocation: If two
nonhomologous chromosomes exchange MOLECULAR CYTOGENETICS
pieces
- balanced translocation carriers: have a
tendency, independent of age, to produce Merging classic cytogenetics with DNA
germ cells with an abnormal translocation technology have facilitated precise
chromosome definitions of chromosome abnormalities,
location, and origins, including unbalanced
MICRODELETION AND MICRODUPLICATION translocations, accessory or marker
chromosomes, and gene mapping
Prader- Willi Syndrome- hypotonia,
hypogonadism, obesity,distinct face, short Fluorescent in situ hybridization (FISH)
stature, mild developmental delay -one approach to chromosome
identification
Angelman Syndrome- microcephaly, - chromosome-specific DNA probes adhere
macrosomia, ataxia , excessive laughter ,  to complementary regions located on
seizures, severe mental retardation specific chromosomes
- allows improved identification of
Miller Dieker Syndrome - type I lissencephaly, chromosome location and number in
dysmorphic face, seizures, cardiac anomalies, metaphase spreads or interphase cells
developmental delays
Comparative genomic hybridization (CGH)-
can detect and map changes in specific
regions of the genome.
DUPLICATION

Duplications- more common than

deletions and are less harmful because
there is no loss of genetic material.
- happens when a part of the chromosome
is duplicated
- the resulting phenotype often includes Fragile X syndrome- is the second most
mental commonly inherited cause of moderate
impairment or birth defects. Duplication may intellectual disability after
involve part of a gene, a whole gene, or a series Down syndrome
of genes
housekeeping genes- genes expressed in a
wide variety of cells and are involved in
basic cellular metabolic functions, such as
INVERSION
nucleic acid and protein synthesis,
Inversion- a chromosomal aberration in which cytoskeleton and organelle biogenesis, and
a segmentof a chromosome is reversed. nutrient transport and
- Paracentric inversion: is other cellular mechanisms.
confined to a single arm of the chromosome
- Pericentric inversion: involves both Regulation of gene expression- an essential
arms and includes the centromere; carriers of aspect of developmental biology
pericentric inversions risk having offspring with
birth defects because of unequal crossing over Epigenetic regulation- refers to changes in
and malsegregation at meiosis phenotype (appearance) or gene
expression caused by mechanisms
ISOCHROMOSOMES other than changes in the underlying DNA
sequence

Isochromosome- results when the Genomic imprinting- an epigenetic process

centromere divides transversely instead of in which the allele inherited from the
longitudinally, mother or father is marked by methylation
creating a chromosome in which one arm is (imprinted), silencing the gene and allowing
missing and the other is duplicated. expression of the nonimprinted gene from
- This chromosome appears to be the other
the most common structural abnormality of the parent.
X chromosome. Persons with this aberration
often have short stature and the other stigmata DEVELOPMENTAL SIGNALLING PATHWAYS
(visible evidence of
disease) of Turner syndrome; these Birth defects- caused by mutations or
characteristics are related to the loss of an arm alterations in any of the signaling pathways
of an X chromosome that regulate embryogenesis

Signalling pathways- cell autonomous and

BIRTH DEFECTS CAUSED BY MUTANT GENES alter the differentiation of only that
particular cell
Between 7% and 8% of birth defects are caused
by gene defects transcriptional factors- act by influencing
the pattern of gene expression of adjacent
Mutation- usually involving a loss or change in cells.
the function of a gene, is any permanent, - these shortrange signal controls can act as
heritable change in the sequence of genomic simple on-off switches (paracrine signals);
DNA. those called morphogens elicit many
responses in target cells depending on their
level of expression (concentration).
Sonic hedgehog- protein that initiate
development of signaling pathway CRITICAL PERIOD OF HUMAN DEVELOPMENT
- sets off a chain of events resulting in
activation and repression of target cells by
The most crucial period for the growth of your
transcription factors in the GLI family
unborn child is the first trimester. Your baby's
- Sporadic and inherited mutations in the bodily structure and organ systems grow
human SHH gene leads to holoprosencephaly throughout this time. During this time, the
majority of miscarriages and birth abnormalities
Smith-LemliOpitz syndrome- defects in happen.
cholesterol biosynthesis, such as in the ● The critical period for brain
autosomal recessive disorder development is from 3 to 16 weeks,
but development may be disrupted
after this because the brain is
differentiating and growing rapidly at
birth.
● Teratogens may produce mental
deficiency during the embryonic and
fetal periods
● Development of permanent teeth may
be disrupted by tetracyclines from 14
weeks of fetal life up to 8 years after
birth
● Environmental disturbances during the
first 2 weeks after fertilization may
interfere with cleavage of the zygote
BIRTH DEFECTS CAUSED BY ENVIRONMENTAL and implantation of the blastocyst and
FACTORS may cause early death and
spontaneous abortion of an embryo
Teratogen- is any agent that can ● Teratogens acting during the first 2
produce a birth defect (congenital anomaly) or weeks kill the embryo or their
increase the incidence of a defect in the disruptive effects are compensated for
population by powerful regulatory properties of
the early embryo.
- do not appear to cause defects until cellular
differentiation has begun

Environmental factors (e.g., infections, drugs)

-may simulate genetic conditions, as when two
or more children of normal parents are
affected. An important principle is that not
everything that is familial is genetic

Principles of Teratogenesis
When considering the possible teratogenicity
of a drug or chemical, three important
principles must be considered:
1. Critical periods of development
2. Dose of the drug or chemical
3. Genotype (genetic constitution) of the
embryo
 ● By being aware of these teratogens,
mothers can avoid exposing their
embryos to these harmful substances.
● Drugs, chemicals, food additives, and
pesticides are teratogenicity tested to
find substances that could lead to
abnormalities during human
development.

DRUGS AS TERATOGEN
● Taking both prescription and over-the-
counter medications is unexpectedly
high during pregnancy. roughly 40% to
90% of women use one non-
prescription drug daily.

CIGARETTE SMOKING
● Low birth weight (<2000 g) is the
chief predictor of infant death.
● Known to cause intrauterine
growth restriction.
● Heavy smokers have an
increased frequency of
premature delivery.
● increase in the incidence of
conotruncal and atrioventricular
septal heart defects associated
(for clear photo see page 473 of Developing Human
with maternal smoking in the first
by Moore)
trimester
● Limb deficiencies
DOSE OF DRUGS OR CHEMICALS ● Nicotine constricts uterine blood
● Consequently, animal studies are not vessels, decreasing uterine
readily applicable to human pregnancies. blood flow and lowering the
For a drug to be considered a human supply of oxygen and nutrients
teratogen, a dose-response relationship available to the embryo or fetus.
has to be observed, and the greater the
exposure during pregnancy, the more The major source : Cadmium-
severe the phenotypic effect Interfere with the metabolism of
elements such as Zinc, Copper, Iron,
Selenium. Results in:
➔ Low birth weight
GENOTYPE OF EMBRYO
➔ Sirenomelia (mermaid
● Examples abound in experimental animals, syndrome)
and several suspected human cases ➔ Amelia (shortness or absence of
demonstrate the existence of genetic limbs)
variations in teratogen reaction. For
example phenytoin is a well-known human ALCOHOL
teratogen, for instance. ● Alcohol consumption, whether
moderate or excessive, during
the first trimester of pregnancy
HUMAN TERATOGENS
 may affect the embryo's or fetus's
growth and morphogenesis.
● 1-2% of women who are
childbearing age are affected.
● A certain pattern of problems, such
as prenatal and postnatal growth
deficiencies, mental deficiencies,
and other defects, are present in
newborns born to chronic alcoholic
mothers.
● Fetal alcohol syndrome (FAS) is
also a defect associated with
alcohol intake and is seen in 1 to 2
infants in 1000 live births.
● FAS is associated with a pattern of
defects like Microcephaly (small
neurocranium), short palpebral
fissures, epicanthal folds, maxillary
hypoplasia, short nose, thin upper Androgens and Progestogens
lip, abnormal palmar creases, joint ● Progestogens is a natural or
defects, and congenital heart synthetic substance that
disease. promotes biologic changes. It is
● Moderate consumption (1-2os/day) responsible for the production of
may cause neiro-developmental progestins..
impairments- Fetal Alcohol Effects ● The progestins ethisterone and
● Fetal Alcohol Spectrum Disorder norethisterone should be
is the preferred term for prenatal avoided as medications.
alcohol effects. ● Additionally, progesterone
● Fetal Alcohol Syndrome- exposure might result in
microcephaly, short palpebral glandular hypopadias and
fissure, epicanthal folds, maxillary cardiovascular abnormalities.
hypoplasia, short nose, thin upper ● Diethylstilbestrol (DES), which
lip, joint anomalies and congenital is known to be a synthetic
heart disease nonsteroidal estrogenic
● Total abstinence of alcohol during compound, is a human teratogen
pregnancy is advised that cause microscopic
congenital abnormalities of the
uterus and vagina- Vaginal
Adenosis, Transverse Vaginal
Ridges and Adenocarcinoma
of the Vagina
● Following maternal treatment,
male fetuses exposed to DES in
utero have a higher frequency of
genital tract malformations, such
as epididymal cysts and
hypoblastic testes.

Tetracyclines
● Yellow discoloration of the
primary teeth
 ● Exposure between the fourth and hernias.
ninth month of pregnancy can result
in enamel hypoplasia, tooth ● Pregnant women who take
discolouration that ranges from valproic acid have a higher risk
yellow to brown, and slowed long of having babies with heart, limb,
bone growth. and craniofacial deformities as
well as postnatal cognitive
Streptomycin- deafness developmental delays. Defects
in the neural tube are also more
Antibiotics likely.
● Antibiotics such as Tetracyclines
● Small doses of tetracyclines during Antineoplastic Agents
the third trimester can produce ● Tumor-Inhibiting Chemicals are
staining of the deciduous and highly teratogenic
permanent teeth. ● Results in intrauterine death
● Tetracycline therapy during the 4th Busulfan and 6-mercaptopurine
to 9th month can cause defects like ● Produced multiple severe
enamel and hypoplasia, yellow abnormalities, but neither drug
discoloration of the teeth and alone caused major defects
diminished length of long bones. Methotrexate
Folic acid antagonist and a
ANTICOAGULANTS derivative of aminopterin
● Warfarin is a known teratogen that Multiple skeletal and other
causes hypoplasia of nasal congenital anomalies
cartilage, stippled epiphyses, Indicated in patients with severe
hypoplastic phalanges, eye rheumatic disease
anomalies, mental retardation and ● Corticosteroids
various CNS defects with mothers Low doses, including cortisone
who took this drug during the critical and hydrocortisone, do not induce
period of embryonic development. cleft palate or any other defect in
The period of greatest sensitivity human embryos.
is between 6 and 12 weeks after ● ACE Inhibitors
fertilization. Results in: If a fetus is exposed to this
● Heparin is not a teratogen and medication, it raises the risk of fetal
does not pass the placental death, hypoplasia of the calvarial
membrane. bones, IUGR, cardiovascular
problems, and renal failure.
ANTICONVULSANTS:
● Trimethadione is a teratogen that ● Psychotropic Drugs
causes Fetal trimethadione When administered during
syndrome with features of growth pregnancy, lithium can lead to
retardation, developmental delay, V- heart and blood vessel problems if
shaped eyebrows, low-set ears, "in the view of the physician, the
cleft lip and palate, cardiac, potential advantages outweigh the
genitourinary and limb defects. possible dangers."
● Phenytoin causes fetal hydantoin Benzodiazepines (diazepam and
syndrome with features of IUGR, oxazepam)
microcephaly, mental deficiency,
eyelid ptosis, inner epicanthal folds, Selective Serotonin Reuptake
broad depressed nasal bridge, nail Inhibitors (SSRIs)
and/or distal Treat depression during pregnancy
phalangeal
hypoplasia,ridged frontal suture and
 Increased risk of atrial and ventricular ● Defects: increased abortions,
septal defects, persistent pulmonary fetal defects, IUGR, and
hypertension, and neurobehavioral functional deficits
disturbances ● Defects of lead poisoning may
Mechanism: SSRIs block catecholamine also include:
transport, which affects placental blood flow - Mental retardation
● Illicit Drugs (Street Drugs) - Movement disorders
- There is also concern about - Low IQ
the longterm postnatal - School performance
developmental effects of - Behavioral changes and growth
methadone. retardation at later stages of life
Cocaine
Widely used among women of childbearing
age
POLYCHLORINATED BIPHENYLS
● Defects are: prematurity, IUGR,
microcephaly, cerebral infarction, ● are teratogenic substances that
urogenitalabnormalities, result in IUGR and skin toxicity
neurobehavioral disturbances, discoloration. These substances
neurologic abnormalities, placental are primarily obtained from
abruption, spontaneous abortion, diet.It's likely that sport fish in
Methadone North America were taken from
● Used during withdrawal treatment of morphine and polluted waters.
heroin addiction
● Effect: CNS dysfunction, lower birth ● Sources of PCB
weights, and smaller head circumferences - Contaminated food (90%)
- Accidental release from
existing electrical
ENVIRONMENTAL equipment
CHEMICALS AS - Improper incineration
TERATOGENS - Occupational Exposure
- Hazardous Waste Site
Organic mercury
● Found in diets consists of fish with INFECTIOUS AGENTS AS
high levels of organic mercury TERATOGENS
● Defects: Fetal Minamata disease
(neurologic and behavioral
disturbances resembling cerebral 1. Congenital Rubella
palsy) ● German Measles
● Severe brain damage, mental ● The fetus acquires the infection
deficiency, and blindness have transplacentally; the virus
been detected in infants of crosses the placental membrane
mothers who received and infects the embryo or fetus
methylmercury in their food. This ● Defects of Congenital Rubella
liquid metal is a teratogen that Syndrome:
causes cerebral atrophy, - Cataracts, cardiac defects, and
spasticity, seizures, and mental deafness
deficiency. - mental deficiency,
Lead chorioretinitis, glaucoma
● Known to be abundant in work ● Infants have birth defects when
places and environment disease occurs during the first 4
to 5 weeks after fertilization
2. Cytomegalovirus Maternal infection is acquired by
● Member of herpesvirus family two routes
● Fetuses with this virus are often 1.) Eating raw or poorly cooked
delivered prematurely. CMV is the meat (pork or lamb)
most common viral infection of the containing Toxoplasma cyst
fetus, occurring in approximately 1% 2.) Close contact with domestic
of neonates. animals (e.g., cats) or
● Most pregnancies end in infected soils
spontaneous abortion when the ● Effects: Intracranial
infection occurs during the first calcifications, chorioretinitis.
trimester. It is the leading cause of Mental deficiency,
congenital infection with morbidity at microcephaly, and
birth microphthalmia, hydrocephaly
● Leading cause of morbidity at birth
7. Congenital Syphilis
3. Herpes simplex virus ● Treponema pallidum causes
● Defects: cutaneous lesions, syphilis
microcephaly, microphthalmia, Spiral microorganism
spasticity, retinal dysplasia, and ● Crosses the placental
deficiency membrane as early as 6-8
weeks
4. Varicella (chicken pox) and Herpes ● Primary Maternal Infections
zoster (shingles) (acquired during pregnancy)
Causes serious fetal infection and
● Caused by varicella-zoster virus birth defects
● There is a 20% chance of these or ● Secondary maternal infection
other defects when the infection (acquired before pregnancy)
occurs during the critical period of Seldom results in fetal disease
development ( and birth defects
● Infection occurs during first 2
trimesters
● Defects: skin scarring, muscle RADIATION AS TERATOGENS
atrophy, hypoplasia of limbs,
rudimentary digits, eye and brain
damage, and mental deficiency Exposure to high levels of ionizing
radiation may injure embryonic cells,
5. Human immunodeficiency virus resulting in cell death, chromosome
● Causes acquired immunodeficiency injury, mental deficiency, and deficient
syndrome (AIDS) physical growth.
● There is conflicting information on
the fetal effects of in utero infection ● Defects: growth retardation,
microcephaly, spina bifida
with HIV
● Defects: growth failure, cystica and pigment changes in
the retina, cataracts, cleft palate,
microcephaly, and specific
skeletal and visceral
craniofacial features
abnormalities, and mental
● Transmission occur at time of
deficiency
delivery
● CNS is affected by radiation
● Breastfeeding increases the
● 8-16 weeks after fertilization is
transmission to the neonate.
the period of greatest sensitivity
6. Toxoplasmosis
for radiation damage brain
● Caused by Toxoplasma gondii
 1. Ultrasonic Waves ● A major issue is determining the
● Pregnancy uses ultrasonography genetic the prevalence of
frequently for deformities like cleft lip and
● Prenatal care and diagnosis of palate (CLP) is that there are
embryos or fetuses. a critique unknown numbers of the
examination of the safety of relevant genes compared to a
obstetric ultrasound reveals that single gene).
there are no known negative
consequences for the fetus from ● 2 approaches of examining
the regular use of ultrasonography contribution of genetic factors to
diagnostic testing. CLP:
1. Large scale family studies
2. Linkage and association
MATERNAL FACTORS AS studies with specific genetic
TERATOGENS markers

● Phenylketonuria
- Hyperphenylalaninemia and SUMMARY OF BIRTH DEFECTS
homozygous phenylalanine
hydroxylase deficiency increase the
likelihood of having children with ● Birth defects are any type of
microcephaly, heart abnormalities, structural abnormalities that are
mental deficiencies, and IUGR. present at birth. The defect may be
Prevented by putting the mother on macroscopic or microscopic and on
a restricted-phenylalanine diet the surface or within the body.
before and throughout pregnancy.
The four clinically significant
MECHANICAL FACTORS AS types of birth defect are:
TERATOGENS - malformation
● Amniotic fluid absorbs mechanical - disruption
pressures, protecting the embryo - deformation
from most external trauma. - dysplasia.
● A significantly reduced quantity of ● Approximately 3% of neonates
amniotic fluid (oligohydramnios) have an obvious major defect.
may result in mechanically induced ● Additional defects are
deformation of the limbs, such as detected after birth; the
hyperextension of the knee
incidence is approximately
6% among 2-year-old children
BIRTH DEFECTS CAUSED BY and 8% among 5-year-old
MULTIFACTORIAL INHERITANCE children.
● Some birth defects are
● Multifactorial features are frequently caused by genetic factors and
single, significant flaws, such as few are caused by
such as isolated cleft palate, cleft environmental factors,
lip, and neural tube abnormalities infectious agents,
(such as environmental chemicals
pyloric stenosis, spina bifida ● Most common defects result
cystica), meroencephaly, and hip from a complex interaction
dislocation that develops from birth between genetic and
environmental factors.
● Teratogenic exposure occurs in the
first two weeks of development.
● Usually, substances either harm the
embryo or have no impact.
● Teratogenic agents emerged
throughout the organogenetic era.
disrupt growth and could result in
large birth defects. Teratogens may
exist during the fetal period and
anomalies in morphology and
function, especially those of the
brain and eyes.