BIRTH DEFECT

PENGERTIAN

Congenital malformation
Congenital physical anomalies at birth (organ, part of organ, region
of body)
an abnormality of the structure of a body part (macros or
microscopic), on the surface or within the body)
Mix factors: genetics (chromosomal abnormality), intrauterine
environment (oligohydramnion; lack of nutrients), no known
(idiopathic), infection (virus)
Any substance that causes birth defects is known as a teratogen
Consist:
Congenital malformation (first semester): intrinsically abnormal
development process...abnormal from the beginning
Disruption: results from the extrinsic breakdown of, or an
interference with, an originally normal development
process..exposure teratogens...can not be inherited
Deformation (2nd and 3rd semester): abnormal form, shape or
position of apart of the body results from mechanical forces
Dysplasia : abnormal organization of cells into tissuesand its
morphologic results-dyshistogenesis
A syndrome isd a pattern of multiple anomalies
Congenital anomalies resulted in about 510,000 deaths globally in 2010

Siamese twins- conjoined

twins

Ambras syndrome

Fused limb

cyclopia

progeria

Vestigial tail

statistics
The cause of 40-60% of congenital anomalies in
humans is unknown.
These are referred to as sporadic, a term that implies
an unknown cause, random occurrence regardless of
maternal living conditions, and a low recurrence risk for
future children.
For 20-25% of anomalies there seems to be a
"multifactorial" cause, meaning a complex interaction of
multiple minor genetic anomalies with environmental
risk factors.
Another 10-13% of anomalies have a purely
environmental cause (e.g. infections, illness, or drug
abuse in the mother).
Only 12-25% of anomalies have a purely genetic cause.
Of these, the majority are chromosomal anomalies

 Genetic causes of congenital anomalies include

inheritance of abnormal genes from the parents, as
well as new mutations in one of the germ cells that
gave rise to the fetus.
Environmental causes of congenital anomalies are
referred to as teratogenic.
These are generally problems with the mother's
environment.
Teratogens can include dietary deficiencies, toxins, or
infections. For example, dietary deficiency of maternal
folic acid is associated with spina bifida. Ingestion of
harmful substances by the mother (e.g., alcohol,
mercury, or prescription drugs such as phenytoin) can
cause recognizable combinations of birth defects.

Birth defect,
Major congenital abnormalities
Minor congenital anomaly/functional
defect

 Now various techniques are available to detect

congenital anomalies in fetus before birth
Several infections which a mother can contract
during pregnancy can also be teratogenic. These
are referred to as the TORCH infections
The greatest risk of a malformation due to
environmental exposure to a teratogen (terato =
monster, gen = producing) between the third and
eighth week of gestation.
Before this time, any damage to the embryo is
likely to result in fatality, and the baby will not
be born. After eight weeks, the fetus and its
organs are more developed and less sensitive to
teratogenic incidents

 About 3% of newborns have a "major physical

anomaly", meaning a physical anomaly that has
cosmetic or functional significance.
Congenital anomalies involving the brain are the
largest group at 10 per 1000 live births, compared
to heart at 8 per 1000, kidneys at 4 per 1000, and
limbs at 1 per 1000. All other physical anomalies
have a combined incidence of 6 per 1000 live births.
Congenital anomalies of the heart have the highest
risk of death in infancy, accounting for 28% of infant
deaths due to congenital anomaly, while
chromosomal anomalies and respiratory anomalies
each account for 15%, and brain anomalies about
12%.

Defects with female predominance

Congenital hip dislocation1 : 5.2;
Anencephaly 1 : 1.9;
Craniocele 1 : 1.8
Aplasia of lung 1 : 1.51
Spinal herniation 1 : 1.4
Diverticulum of the esophagus 1 : 1.4
Stomach 1 : 1.4

Neutral defects
Hypoplasia of the tibia and femur 1 : 1.2
Spina bifida 1 : 1.2
Atresia of small intestine 1 : 1
Microcephaly 1.2 : 1
Esophageal atresia 1.3 : 1;
Hydrocephalus 1.3 : 1

Defects with male predominance

Diverticula of the colon 1.5 : 1
Atresia of the rectum 1.5 : 1;
Unilateral renal agenesis 2 : 1;
Schistocystis 2 : 1
Harelip 2 : 1;
Bilateral renal agenesis 2.6 : 1
Congenital anomalies of the genitourinary
system 2.7 : 1
Pyloric stenosis, congenital 5 : 1
Meckel's diverticulum More common in boys
Congenital megacolon More common in boys

 Causes
exogenous causes
exogenous toxic (teratogenetic agents
ionizing radiations
fetal infections (maternofetal infections

genetics
genetic causes (or intrinsic causes)
(genetic malformative diseases)
chromosomal anomalies (chromosomal
malformative diseases)
numerical chromosomal anomalies (e.g.
trisomy 21)

gene mutations (monogenic

malformative diseases)
Joubert syndrome, Meckel syndrome and
related syndromes: TMEM216
cleft lip with and without cleft palate: MAFB
and ABCA4

 A limb anomaly is called a dysmelia

These include all forms of limbs
anomalies, such as amelia,
ectrodactyly, phocomelia, polymelia,
polydactyly, syndactyly,
polysyndactyly, oligodactyly,
brachydactyly, achondroplasia,
congenital aplasia or hypoplasia,and
cleidocranial dysostosis

acheiria

 Congenital anomalies of the heart

include patent ductus arteriosus,
atrial septal defect, ventricular septal
defect, and tetralogy of fallot

 Congenital anomalies of the nervous

system include neural tube defects
such as spina bifida, meningocele,
meningomyelocele, encephalocele
and anencephaly.

Microtia - anotia

 Teratogens (birth defects) any agent

or non-genetic factor that produces
permanent abnormal embryonic
physical development of physiology.
Historical Events:
1941: Rubella (blindness, Congenital
Heart defects)
1950s: Methylmercury (neurotoxicity)
1960s: Thalidomide (phocomelia)
1970s: Alcohol (fetal alcohol syndrome)

 Principles of Teratology:
All or none phenomenon (from conception
to implantation)-prenatal death
Dose dependency
Critical periods for certain effects
Duration of exposure
Host suseptibility
Drug interactions
BEST: Single drug; lowest dose

 Critical periods during human development:

Embryonic 3-8weeks; Gestational age 510weeks
Effect of teratogen by (gestational) week
exposure:
1-6 weeks: CNS
2-7 weeks: Heart
3-8 weeks: Extremities
3-8 weeks: Eyes
5-8 weeks: Palate
6-10 weeks: External Genitalia

 Thalidomide:
Introduced in 1956 as a seditive & antinausea agent
Withdrawn in 1961
Discovered to be human teratogen
causing absence of limbs or limb
malformations in newborns
5000-7000 infants effected
Resulted in new drug testing rules

Pre-Embryonic Stage:
Time of fertilization & up to implantation
First 2 weeks of gestation
Exposure to teratogens in this period may lead to improper
implantation & spontaneous abortion, Also called All or
None.
Critical Period- Embryonic Period:
From day 14-18 to day 54-60 post-conception (this is the
critical period)
Period of most extensive organ differentiation (the heartfirst 38days; arms/legs-first 49days; teeth-first 56days, etc.)
Exposure to teratogens during this period can cause
structural and functionatl birth defects.
Fetal Period:
From day 56 of gestation to delivery
Differentiation of the palate, external genitalia, and ear are
examples for this period. Structural defects as well as fetal
growth retardation can occur.

Known or strongly suspected Teratogens (Drugs &

Chemicals)
Alcohol : IUGR, microcephaly
Androgens (testosterone): masculinization of
female fetus
Carbamezepine, Phenytoin, Valproic Acid (cleft
palate)
Folic Acid Antagonist (Hyper/Hypobilrubemia
Cocaine; IUGR, microcephaly, urogenital anomaly
Lead, Mercury+
Lithium (Bipolar meds. -cardiac defects)
Tetracycline (discolor teeth/effect bone growth)
Thalidomide: anomaly of limb -meromelia

 Known or Strongly Suspected

Teratogens (INFECTIONS)
CMV-cytomet.virus:microcephaly,
chorioretinitis, cerebral palsy, sensoroneural
deafness
Rubella: cataract, sensoroneural deafness,
cardiac anomaly, microcephaly
Syphilis: hydrocephalus, congenital
deafness, mental retardation
Toxoplasmosis: microcephaly, mental
retradation, hearing loss
Varicella virus: hydrocephaly,mental
retardation

 Down Syndrome
Down syndrome (trisomy 21) is the most common and best known
chromosomal abnormality. It is a trisomy condition, where there is an
extra, third chromosome rather than just the standard two.
With Down syndrome, physical and mental development is delayed.
Infants with Down syndrome tend to be quiet and passive with
somewhat limp muscles.
Most children with Down syndrome have a lower than average IQ.
Children with Down syndrome tend to have a small head, a broad,
flat face with slanting eyes and a short nose. The tongue is large and
their ears are small and set low in the head. The hands are short and
broad, with a single crease across the palm.
About half of all children with Down syndrome have heart defects
and many develop thyroid disease . They are also prone to hearing
and vision problems.
Down syndrome can be diagnosed before birth.
Your physician may be able to recognize some of the distinctive
physical characteristics of an infant with Down syndrome during an
ultrasound. The diagnosis is confirmed by testing the infant's
chromosomes for trisomy 21 or other disorders of the 21st
chromosome. After the diagnosis is made, doctors use further tests
to detect abnormalities associated with Down syndrome.

 Turner Syndrome

In Turner syndrome, girls are born with one of the two X chromosomes
partially or completely missing.
Many newborns with Turner syndrome have swelling on the backs of
their hands and tops of their feet. Swelling or loose folds of skin are
often evident on the back of the neck. Many other abnormalities often
develop, including a webbed neck, a low hairline at the back of the
neck, a broad chest with wide-spaced nipples, and poorly developed
nails.
As a girl with Turner syndrome gets older, she has no menstrual periods
and the breasts, vagina, and labia remain childlike rather than
undergoing the changes of puberty. The ovaries usually do not contain
developing eggs. A girl or woman with Turner syndrome is almost
always short, and obesity is common.
Other disorders often develop, such as:
Heart defects
Kidney and eye defects
Diabetes
Hypothyroidism
Osteoporosis
Bleeding from abnormal blood vessels in the intestines
Many girls with Turner syndrome have difficulty in assessing visual and
spatial relationships and have problems with planning and attention.
They tend to score poorly on certain performance tests and in
mathematics, even if they achieve average or above-average scores on
verbal intelligence tests. Intellectual disability is uncommon

 Klinefelter Syndrome
is a disorder in which male infants are born with an extra X
chromosome (XXY).
While most boys with Klinefelter syndrome have normal or
slightly decreased intelligence, many have speech and
reading disabilities and difficulties with planning.
Most also have problems with language skills. Early problems
with language may lead to problems with social interactions
that affect behavior. Although physical characteristics can
vary greatly, most boys with the condition are tall with long
arms but otherwise normal in appearance.
Puberty usually occurs at the normal time, but the testes
remain small. At puberty, growth of facial hair is minimal,
and the breasts may enlarge somewhat. Men and boys with
the syndrome are usually infertile.
Men with Klinefelter syndrome develop diabetes mellitus ,
chronic lung disease, varicose veins , hypothyroidism , and
breast cancer more often than other men.
The syndrome usually is not suspected until puberty when
most of the symptoms develop..

Klinefelter Syndrome