Congenital anomalies (birth defect)

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1. CONGENITAL ANOMALIESCONGENITAL ANOMALIES
(Birth defects(Birth defects((
QURATULAIN MUGHALQURATULAIN MUGHAL
ISRA UNIVERSITYISRA UNIVERSITY
BATCH IVBATCH IV
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2. CONGENITAL ANOMALYCONGENITAL ANOMALY

It is a structural abnormality of any It is a structural abnormality of any
type that is present at birth.type that is present at birth.
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3. EITIOLOGYEITIOLOGY

Congenital anomalies may be induced by:Congenital anomalies may be induced by:

geneticgenetic

environmental factorsenvironmental factors
NOTE:NOTE:
Most common congenital anomalies, Most common congenital anomalies,
however, show the family patterns however, show the family patterns
expected of expected of multifactorial inheritancemultifactorial inheritance
(determined by a combination of genetic (determined by a combination of genetic
and environmental factors).and environmental factors).
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4. INCIDENCE/PREVALENCEINCIDENCE/PREVALENCE

About About 3%3% of all live born infants have an of all live born infants have an
obvious major anomaly. obvious major anomaly.

The incidence is about The incidence is about 6%6% in 2-year-olds in 2-year-olds
and and 8%8% in 5-year-olds. in 5-year-olds.

Congenital anomalies may be Congenital anomalies may be single or single or
multiplemultiple and of and of minor or majorminor or major clinical clinical
significance. significance.
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5. PATHOPHYSIOLOGYPATHOPHYSIOLOGY

During the first During the first 2 weeks of development2 weeks of development, ,
teratogenic agents usually teratogenic agents usually killkill the embryo or the embryo or
have have no effectno effect. .

During the During the organogenesis periodorganogenesis period (3rd (3rd –– 8th 8th
weeks), teratogenic agents disrupt development weeks), teratogenic agents disrupt development
and may cause and may cause major congenital anomalies. major congenital anomalies.

During the During the fetal periodfetal period (9th week (9th week –– 9th month) 9th month)
teratogens may produce teratogens may produce morphological and morphological and
functional abnormalitiesfunctional abnormalities, particularly of the brain , particularly of the brain
and eyes. and eyes.
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6. Causes of congenital anomalies
1-Genetic factors such as chromosomal
abnormalities and mutant genes.
2-Environmental factors e.g.: the mother had
German measles in early pregnancy will
cause abnormality in the embryo.
3-Combined genetic and environmental factors
(mutlifactorials factors).
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7. Types of abnormalities
1-Malformations: this occurs during the
formation of the structures of the organ
(during organogenesis) results in partial or
complete non formation or alterations in the
normal structure. This occurs in the 3
rd
to the
8
th
week of gestation. Ex. Cleft lip and or cleft
palate.
2-Disruptions: results in morphological
change of the already formed structure due to
exposure to destructive process. e.g.:
vascular accidents leading to intestinal
atresia, amniotic band disruption.
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8. Types of abnormalities
3-Deformations: due to mechanical
forces that affect a part of the fetus over
a long period. Ex: talipes equinovarus
deformity.
4-Syndrome: is a group of anomalies
occurring together due to a common
cause .
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9. 
The genetic factors leading to congenital The genetic factors leading to congenital
anomalies may be due to chromosomal anomalies may be due to chromosomal
abnormalities, gene mutations or may be abnormalities, gene mutations or may be
multifactorial.multifactorial.

Chromosomal abnormalitiesChromosomal abnormalities occur due to: occur due to:
- - late maternal agelate maternal age at the time of pregnancy at the time of pregnancy
(leads to (leads to
chromosomal non-disjunction), chromosomal non-disjunction),
- - radiationradiation (causes chromosome deletions, (causes chromosome deletions,
translocations or breaks), translocations or breaks),
- - virusesviruses as German measles, as German measles,
- - autoimmune diseasesautoimmune diseases, ,
- and some - and some chemical agentschemical agents as anti-mitotic as anti-mitotic
drugs.drugs.
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10. 
- - Chromosomal abnormalities are classified Chromosomal abnormalities are classified
into numerical and structural.into numerical and structural.

Numerical chromosomal Numerical chromosomal
anomaliesanomalies are divided into: are divided into:
1- 1- polyploidypolyploidy as as triploidytriploidy ( a fetus with ( a fetus with
69 chromosomes) and 69 chromosomes) and tetraploidytetraploidy where where
the fetus has 92 chromosomes. the fetus has 92 chromosomes.
Polyploidy leads to severe congenital Polyploidy leads to severe congenital
anomalies and early abortion.anomalies and early abortion.

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11. 2- 2- AneuploidyAneuploidy (one or more chromosomes is added or (one or more chromosomes is added or
missed) as in: missed) as in:
Down syndrome (trisomy 21),Down syndrome (trisomy 21),

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12. 
Turner syndromeTurner syndrome ((45,X or a female missing one X), and ((45,X or a female missing one X), and
Klinefelter syndromeKlinefelter syndrome (47,XXY or a male person with an (47,XXY or a male person with an
extra X chromosome).extra X chromosome).
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13. 
Structural chromosomal anomaliesStructural chromosomal anomalies
include chromosomal deletion, duplication, include chromosomal deletion, duplication,
translocation, inversion, and ring and iso translocation, inversion, and ring and iso
chromosomes. It may also lead to severe chromosomes. It may also lead to severe
congenital anomalies or fetal death.congenital anomalies or fetal death.
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14. Environmental factors
1) Infectious Agents:1) Infectious Agents:
1-Infectious agents include a number of viruses:
Rubella used to be a major problem. It causes cataract,
glaucoma, heart defects and deafness.
Cytomegalovirus :The infection is often fatal and if not
meningoencephalitis produce mental retardation.
Herpes simplex, varicella and human immunodeficiency
viruses are other examples.
2- Toxoplasmosis
3- Syphilis : leads to congenital deafness and mental
retardation.
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15. Environmental factors Cont.
22((RadiationRadiation : :
Ionizing radiation kills rapidly proliferating cells, producing
any type of birth defect depending upon dose and stage
of development. Ex. Atomic bomb on Hiroshima and
Nagasaki.
Exposure of the pregnant woman to a large dose of x- ray
can lead to microcephaly, spina bifida or cleft palate.
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16. Environmental factors Cont.
3) Chemical agents:3) Chemical agents:
There are many dangerous drugs, if have given to the
pregnant female, can produce congenital
anomalies. Ex.:
-Thalidomide (antinauseant sleeping pills) produce
limb defects (phocomelia) and heart malformations.
-Diphenylhydantoin produce facial defects and
mental retardation.

Tetracycline (bone and teeth anomalies)Tetracycline (bone and teeth anomalies)

Aspirin may cause harm in large doses.Aspirin may cause harm in large doses.

Cocaine cause birth defect possibly to its effect as a Cocaine cause birth defect possibly to its effect as a
vasoconstrictor that cause hypoxia.vasoconstrictor that cause hypoxia.

Alcohol cause fetal alcohol syndrome.Alcohol cause fetal alcohol syndrome.
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18. Environmental factors Cont.
5)Hormones:5)Hormones:
Androgenic agents (synthetic progestin to prevent
abortion) cause masculinization of the genitalia of
female embryos.
Endocrine hormones as Diethylstilbestrol cause
malformation of the uterus, uterine tubes, upper
vagina, vaginal cancer and malformed testes.
Insulin which treat diabetes of the mother 
congenital anomalies.
Cortisone (in large doses) may cause cleft palate.
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19. Environmental factors Cont.
6)Maternal Disease:6)Maternal Disease:
Diabetes cause variety of malformations
as heart and neural tube defects.
7)Nutritional deficiency:7)Nutritional deficiency: particularly vitamins
deficiency.
8)Heavy metals:8)Heavy metals: Eg: organic mercury.
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20. PRENATAL DIAGNOSISPRENATAL DIAGNOSIS

Methods of prenatal diagnosis are divided into invasive and non-invasive Methods of prenatal diagnosis are divided into invasive and non-invasive
techniques.techniques.

Technique Time Disorders diagnosedTechnique Time Disorders diagnosed

(in weeks)(in weeks)

A. Non-invasive:A. Non-invasive:

Maternal serum screen:Maternal serum screen:

Alpha feto protein (AFP) 16 Neural tube defects (NTD)Alpha feto protein (AFP) 16 Neural tube defects (NTD)

Triple test 16 Down syndromeTriple test 16 Down syndrome

Ultrasound Ultrasound 18 Structural defects in many 18 Structural defects in many

organs as CNS, heart, organs as CNS, heart,

kidney, and limbs.kidney, and limbs.

B. Invasive:B. Invasive:

- - Amniocentesis Amniocentesis 14-16 Chromosomal and metabolic 14-16 Chromosomal and metabolic

abnormalities, and DNA abnormalities, and DNA

analysis.analysis.

- - Chorionic villus samplingChorionic villus sampling 10-12 As amniocentesis. 10-12 As amniocentesis.

- - Fetal blood sampleFetal blood sample near term As amniocentesis + blood near term As amniocentesis + blood

disorders.disorders.
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21. Technique of Technique of
amniocentesisamniocentesis
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22. Technique of CVSTechnique of CVS
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23. U/S showing U/S showing
polydactylypolydactyly
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24. U/S showing U/S showing
micrognathiamicrognathia
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25. U/S showing Umibilical hernia (associated with Trisomy 18 in 50% of cases)U/S showing Umibilical hernia (associated with Trisomy 18 in 50% of cases)
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26. Fetal therapy
The fetus during intrauterine life can receive treatment
such as:
1- Fetal transfusion (administration of blood transfusion to
the anemic fetus in thalassemia).
2- Medical treatment of thyroid dysfunction or congenital
adrenal hyperplasia of the fetus.
3- Fetal surgery: is possible due to advanced ultrasound
and surgical procedures eg: repair of hernia of the fetus
or in case of hydrocphalus.
4- Stem cell transplantation and gene therapy: it is possible
to transplant stem cells before 18 weeks of gestation of
the fetus without rejection because the
immunocompetence of the fetus doesn’t develop yet.
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28. REFERENCESREFERENCES
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