Genetic Screening

1. GENETIC
SCREENING

2. PRESENTED BY
ULFAT AMIN
MSC PEDIATRIC NURSING

3. INTRODUCTION
Over the last decade, there has been tremendous growth in the knowledge we have about
the role genes play in causing disease. It is estimated that the genetic base of more than
1600 diseases have been identified while even more are being investigated. As
consequences genetic assessment has moved from the realm of the imagination into the
world of reality.

4. • Screening of the genetic disorders is done in order to find the specific genetic
problem which a person is having such as change in chromosomes, genes, or
proteins.
• The result of genetic assessment can confirm or rule out a suspected genetic
condition or help to determine a person’s chance of developing or passing on
genetic disorders.
• Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid or
other tissues.

5. TERMINOLOGY
• GENE: A region of DNA that encodes
function. Or A set of segments of nucleic
acid that contains the information
necessary to produce a
functional RNA product in a controlled
manner.
• CHROMOSOME a molecular "package"
for carrying DNA in Nucleus of the cells.
• GENOME: The entire complement of
genetic material in the chromosome set
of an organism, virus or organelle

6. • ALLELE: one of multiple alternative
forms of a single gene.
• GENOTYPE: The complement
of alleles present in a particular
individual's genome that give rise to the
individual's phenotype.
• PHENOTYPE: The observable physical or
behavioral traits of an organism, largely
determined by the organism's genotype.
• KARYOTYPE: is the number
and appearance of chromosomes in
the nucleus of a cell,

7. GENITICS
• The study of heredity, its transmission and its variation.
OR
• It is the study of how the characteristics of living things
are transmitted from one generation to the next.

8. GENETIC TESTING/ SCREENING
• Testing of a population to identify individuals who are at risk for a genetic disease
or for transmitting a gene for a genetic disease.
OR
• Genetic testing is defined as, “examining a sample of blood or other body fluids or
tissues for biochemical chromosomal or genetic markers that indicate the presence
or absence of genetic disease.”
OR
• Genetic Screening also known as DNA testing, It is the analysis of chromosomes
(DNA), proteins and certain metabolites in order to detect the heritable disease
related genotype, mutations or Karyotypes for clinical purposes.

9. INDICATIONS FOR GENETIC TESTING
• To confirm a specific diagnosis in a symptomatic individual.
• To provide early recognition of a disease, before signs & symptoms occur, for which
effective interventions & therapy exist.
• To identify carriers of a genetic disease for the purpose of maximizing parenthood
planning options e.g Tay-Saches disease.
• To ascertain if a fetus has a clinically significant genetic disorder.
• Figuring out the types or dose of medicine that is best for a certain person.
• To obtain population data on frequency, spectrum & natural history of genetic variations
not currently known to be associated with disease.

10. TYPES OF GENETIC TESTING
Genetic testing can be broadly
divided into two categories:
Diagnostic testing
Screening

11. DIAGNOSTIC TESTING
1. NEW BORN SCREENING
• New born screening is used just after birth
to identify the genetic disorders that can be
treated early in life. All states currently test
the infants for phenylketonuria (a genetic
disorder that causes mental illness if left
untreated) and congenital hypothyroidism
(a disorder of the thyroid gland).

12. DIAGNOSTIC TESTING
• Diagnostic testing is used to diagnose
or rule out a specific genetic or
chromosomal condition. In many cases,
genetic testing is used to confirm a
diagnosis when a particular condition
is suspected based on physical
mutations and symptoms.

13. CARRIER TESTING
• Carrier testing is used to identify people who carry
one copy of a gene mutation that, when present in
two copies causes a genetic disorder. This type of
testing is offered to individuals who have a family
history of genetic disorder. If both parents are
tested, the test can provide information about a
couple’s risk of having a child with a genetic
condition like cystic fibrosis.

14. PRE-IMPLANTATION GENETIC
DIAGNOSIS
• PGD is a procedure used prior to implantation to help
identify genetic defects within embryos. This serves to prevent
certain genetic diseases or disorders from being passed on to the
child. The embryos Investigated in PGD are usually created during
the process of in vitro fertilization (IVF).
• Diagnostic accuracy in PGD is high(98%) both for cytogenic
disorders & single gene disorders.

15. PREDICTIVE AND PRESYMPTOMATIC
TESTING
• Predictive and presymptomatic types of
testing are used to detect gene mutations
associated with disorders that appear
after birth, often late in life.

16. • These tests can be helpful to people who have a family member with a genetic
disorder but who have no features of the disorder in themselves at the time of testing.
• Presymptomatic testing can determine whether a person will develop a genetic
disorder such as hemochromatosis (an iron overload disorder) before any signs or
symptoms appear.
• The result of predictive and presymptomatic testing can provide information about a
person’s risk of developing a specific disorder and help with making decisions about
medical care.

17. PRENATAL DIAGNOSIS
• Prenatal diagnosis employs a variety of techniques to
determine the health and condition of an unborn fetus. Used to
detect changes in a fetus’s genes or chromosomes before birth.
Specifically prenatal diagnosis is helpful for.
a. Managing the remaining weeks of the pregnancy.
b. Determining the outcome of the pregnancy.
c. Planning for problems that may occur in the newborn infant.
d. Deciding whether to continue the pregnancy.

18. PARENTAL TESTING
• This type of genetic test uses special
DNA markers to identify the same or
similar inheritance patterns between
related individuals. Based on the fact
that we all inherit half of our DNA from
the father, and half from the mother.

19. COMMON SCREENING TESTS
1. ULTRASONOGRAPHY
This is a non–invasive procedure that is
harmless to both the fetus and the mother. A
transducer is placed in contact with the
mother’s abdomen and high frequency sound
waves are directed at the fetus. The sound
waves are reflected back through the tissues
and recorded and displayed in real time on a
screen.

20. • The developing embryo can first be visualized at about 6 week’s gestation.
Recognition of the major internal organs and extremities if any abnormality can
be best accomplished between 16 to 20 weeks gestation Although an ultrasound
examination can be quite useful to determine the size and position of the fetus,
the size and the position of the placenta, the amount of amniotic fluid and the
appearance of fetal anatomy.
• There are limitations to this procedure. Subtle abnormalities may not be detected
until later in pregnancy or may not be detected at all e.g. Down’s syndrome
(Trisomy 21).
INDICATION; Screened for structural malformations.

21. AMINOCENTHESIS
• This is an invasive
procedure in which a
needle is passed through
the mother’s lower
abdomen into the amniotic
cavity inside the uterus

22. • For prenatal diagnosis, most amniocenteses are performed
between 14 and 20 weeks gestation. Within the amniotic fluid are
fetal cells (mostly derived from fetal skin) which can be grown in
culture for chromosome analysis, biological analysis and
molecular analysis.
• In the third trimester of pregnancy the amniotic fluid can be
analyzed for determination of fetal lung maturity.

23. INDICATION
Early in pregnancy, amniocentesis is used for diagnosis of chromosomal and
other fetal problems such as:
• Trisomy 21 (Down syndrome)
• Trisomy 18 (Edwards syndrome)
• Trisomy 13 (Patau syndrome)
• Neural tube
defects (anencephaly and Spina
bifida) by alpha-fetoprotein levels.
• It predicts fetal lung maturity, which
is inversely correlated to the risk
of infant RDS.

24. CHORIONIC VILLI SAMPLING
• In this procedure, a catheter is passed via
the vagina through the cervix and into
the developing placenta under ultrasound
guidance. Alternative approaches are
Transvaginal and Transabdominal. The
introduction of the catheter allows
sampling of cells from the placental
chorionic villi

25. • The most common test employed on cells obtained by CVS is chromosome analysis
to determine the Karyotypes of the fetus. The cells can also be grown in culture for
biochemical or molecular biologic analysis. CVS can be safely performed between
9 to 12 weeks gestation.

26. INDICATION
• Abnormal first trimester screen results
• Increased nuchal translucency or other abnormal ultrasound findings.
• Family history of a chromosomal abnormality or other genetic disorder
• Parents are known carriers for a genetic disorder
• Advanced maternal age(AMA) (maternal age above 35). AMA is
associated with increase risk of Down's syndrome and at age 35, risk is
1:400. Screening tests are usually carried out first before deciding if CVS
should be done.

27. TRIPLE/QUADRUPLE SCREEN
• A maternal serum laboratory
screening test that measures the
level of three substances made
by the developing baby and
placenta: α- fetoprotein (AFP),
human chorionic gonadotropin
(HCG), and unconjugated estriol
(uE3).

28. • Dimeric inhibin A has been added to make
the quadruple test. The addition of Dimeric
inhibin A increases the detection rate of Down
syndrome and Trisomy 18 in the quadruple
screen.
• INDICATION: It is a screening test for low-
risk pregnant women to determine
pregnancies at an increased risk for open
neural tube defects, Down syndrome, and
Trisomy 18(Edwards syndrome).

29. FETAL NUCHAL
TRANSLUCENCY(FNT)
• A nuchal scan or nuchal translucency (NT) scan/procedure is a
sonographic prenatal screening scan (ultrasound) to detect cardiovascular
abnormalities in a fetus. It helps to identify higher risks of Down syndrome,
Trisomy 13(Patau syndrome), Trisomy 18 and Turners syndrome(45X). The
ultrasound assesses the amount of the fluid behind the neck of a fetus (known as
the nuchal fold). Increased fluid increases the risk of a chromosomal abnormality.

30. • During this early ultrasound other markers may be looked at such as presence of
nasal bones (in Down syndrome hypoplasia or absence of the nasal bones may be
noted); Short femur or humerus increases the risk of Trisomy, echogenic foci
(bright spots) in the heart can increase the risk of Down syndrome, and
echogenic bowl (bowl looks bright and white) can be associated with
chromosomal abnormalities.
• A serum blood test is performed to determine the level of two hormones, PAPP-A
and β-HCG. Using a combination of the ultrasound and blood test, the risk of
having a baby with Down syndrome is predicted.

31. INDICATION
• Any pregnant woman presenting by 11 to 14 weeks gestation can be
screened. Particularly for women with increased risk or desired screening
for Down syndrome, Trisomy 13, Trisomy 18, or Turners syndrome.

32. PERCUTANEOUS UMBILICAL BLOOD
SAMPLING
• An ultrasound guided needle is inserted
through the abdominal and uterine wall
to the umbilical cord and a sample of
blood is retrieved and sent to the
laboratory for analysis. Procedure is
similar to amniocentesis but requires a
higher level of expertise and experience.

33. INDICATION
• It is usually done when diagnostic information cannot be obtained through
amniocentesis, CVS or ultrasound.

34. FETOSCOPY
• It is the endoscopic procedure that
allows direct visualization of the
fetus through the insertion of a tiny
flexible instrument called fetoscope.
It is inserted through the abdominal
wall and into the uterine cavity.
Ultrasound is used to guide the
placement of the scope

35. • Direct visualization can evaluate the fetus for severe congenital anomalies like
neural tube defects. Fetal blood sample from the umbilical cord can be obtained
and tested for congenital blood disorders such as hemophilia and sickle cell
anemia. Fetal tissue samples (usually skin) can be collected and tested for
genetic diseases.
INDICATION
• It is indicated for any woman at risk for delivering a baby with significant
congenital anomalies
• Used to perform corrective surgery (e.g shunt placement) on the fetus.

36. NEWBORN SCREENING
• Blood screening performed shortly after birth, used to identify many life
threatening genetic illnesses that have no immediate visible effect but can
lead to physical problems, intellectual disability and even death.
• INDICATIONS: Identification of new born so that treatment can begin
early to prevent impact of the disorder, such as severe cognitive
impairment or death.

37. MATERNAL BLOOD SAMPLING FOR
FETAL CELLS
• This is a new technique that makes use of the phenomenon of the fetal blood cells
gaining access to maternal circulation through the placental villi.
• The fetal cells can be stored out and analyzed by a variety of techniques to look
for particular DNA sequences.
• Fluorescence in-situ hybridization (FISH) is one technique that can be applied to
identify particular chromosomes of the fetal cells recovered from maternal blood
and diagnose Aneuploid conditions such as the Trisomies and Monosomy X.

38. MATERNAL SERUM ALPHA FETO
PROTEIN(MSAFP)
• The developing fetus has two major blood proteins – Albumin and Alpha-fetoprotein
(AFP). Since adults typically have only albumin in their blood. MSAFP is a screening
test that examines the level of alpha-fetoprotein in the mother’s blood during
pregnancy.
• This is not a diagnostic test. It is often part of the triple screen test that assesses
whether further diagnostic testing may be needed. Blood is drawn from veins in the
mother’s arm and sent off to a laboratory for analysis. Results are usually returned
between one and two weeks.

39.  If there is neural tube defect in the fetus,
then there is means of escape of more
AFP into amniotic fluid.
 Neural tube defects include
anencephaly (failure of closure at the
cranial end of the neural tube) and
Spina bifida (failure of closure at the
caudal end of the neural tube).

40. MATERNAL SERUM BETA-HCG
• This is most commonly used as a test for pregnancy. Beginning at about a week
following conception and implantation of the developing embryo into the uterus, the
trophoblast will produce enough detectable beta-HCG to diagnose pregnancy.
• The beta-HCG can also be quantified in serum from maternal blood, and this can be
useful early in pregnancy when threatened abortion or ectopic pregnancy suspected
• because the amount of beta-HCG will be lower than expected.

41. • An elevated beta-HCG coupled with a decreased MSAFP suggests Down
syndrome.
• Very high levels of HCG suggest trophoblastic disease (molar pregnancy).
• The absence of a fetus on ultrasonography along with an elevated HCG
suggests a hydatidiform mole

42. FLUORESCENCE IN-SITU HYBRIDISATION
(FISH)
• Fish is a laboratory technique used to visualize where a particular gene
or DNA sequence is located within a person’s genome; this enables
clinical scientists to check for specific chromosomal alteration which
may cause a genetic condition. It is used on samples of blood, chorionic
villi or other material containing cells.

43. The amount of estriol in maternal serum is dependent upon a viable fetus, a
properly functioning placenta and maternal well-being.
substrate for estriol begins as dehydroepiandrosterone (DHEA) made by
the fetal adrenal glands
This is further metabolized in the placenta to estriol.
• The estriol crosses to the maternal circulation and is excreted by the maternal
kidney in urine or by the maternal liver in the bile

44. • The measurement of serial estriol levels in the third trimester will give an
indication of general well-being of the fetus
• If the estriol level drops, then the fetus is threatened and delivery may be done
emeregently.
• Estriol tends to be lower when Down syndrome is present and when there is
adrenal hypoplasia with anencephaly.

45. CONCLUSION
• Today, genetic screening to detect genetic carrier status has
become a mainstay of current clinical practice and can easily be
done by a variety of detection techniques. The aim of
such screening programs is to eliminate the transmission of
severely debilitating diseases, maximise parenthood, decrease
burden of genetic illnesses etc.