1. Genetic testing in the
neonates and children

2. INTRODUCTION
➡ Genetic testing is a type of medical test that identifies changes in genes,
chromosomes, or proteins.
➡ The results of a genetic test can confirm or rule out a suspected genetic
condition or help determine a person's chance of developing or passing on
a genetic disorder.
➡ Many genetic diseases can be diagnosed by a careful clinical history
and examination of patients who have or are suspected to have a genetic
disease.
➡ Recent advances in medical genetics have made it possible to diagnose
many of the genetic disorders when the fetus is inside the uterus itself.

3. ➡ Genetic testing is defined as the tests to detect or exclude an alteration
likely to be associated with a genetic disorder. Most of the time genetic
testing is used to find changes associated with inherited disorders.
➡ Genetic testing is defined as "examining a sample of blood or other
body fluids or tissue for bio-chemical chromosomal, or genetic markers
that indicate the presence or absence of genetic disease.
➡ A genetic testing is analyzing a DNA to look for genetic alteration that
may increase the risk of developing a specific disease or disorder. indicate
➡ It is also defined as type of medical test, identifies changes in
chromosomes, genes or proteins.

4. GENERAL FEATURES OF GENETIC TESTING
➡ Genetic testing is voluntary and it has both benefits and limitations.
➡ Genetic testing is different from the other tests done in clinical
practice. Genetic test of the patient may also provide results for family
members. It may open up ethical or psychological problems.
➡ Genetic counseling is important before advising for any test with
genetic implications.

5. PURPOSE OF GENETIC TEST
➡ Testing to confirm a clinical diagnosis: When a genetic disorder is
suspected on physical characteristics or symptoms, genetic tests are
required for either confirmation of genetic disease or to rule out a suspected
genetic disorder.
➡ Carrier testing/screening: Carrier of particular genetic disorder is an
unaffected individual who carries one copy of a mutated disease. Carrier
testing is done in unaffected genes for individuals who have a family history
of a genetic disorder.
➡ Predictive and Pre-symptomatic testing: Pre-symptomatic testing is most
commonly done for individuals, who have a family member with a genetic
disorder, but are not having features of the disorder themselves at the time of
testing..

6. TIMING OF GENETIC TESTS
➡ Genetic testing before a pregnancy is ideal, because this provides the wide
range of choices if an increased risk of a deleterious genetic condition is detected.
➡ However, most of the genetic tests are done after the woman becomes
pregnant.
➡ Depending on the time of performing these genetic tests, they can be divided
into four types.
➡ Preimplantation: Before conception (i.e. when one or both of the parents are
carriers of a certain trait).
➡ Prenatal testing: These are done after conception.
➡ Newborn or neonatal, childhood screening.
➡ Screening tests in adolescence and adulthood.

7. PREIMPLANTATION GENETIC DIAGNOSIS (PGD/PIGD)
➡ It is also known as embryo screening. It is performed to detect genetic
changes in embryos prior to the implantation.
➡ This can reduce the risk of having a child with a particular genetic or
chromosomal disorder.
➡ The human embryos can be produced using assisted reproductive
techniques such as in-vitro fertilization (IVF).
➡ In vitro fertilization involves removing egg cells from a woman's ovaries
and fertilizing them with sperms outside the body.

8. PREIMPLANTATION GENETIC DIAGNOSIS (PGD/PIGD)
Procedure for fertilization (IVF):
➡ Oocytes are collected from mother's ovary by ultrasound guided technique.
➡ Oocyte is fertilized by husband's sperm by puncturing the oocyte. This is
known as intracytoplasmic sperm injection (ICSI).
➡ The fertilized oocyte is cultured to grow up to 8-10 cell blastocyst stage. One
cell is removed from this early embryo and the DNA is extracted from the cell.
➡ DNA or chromosomal analysis is performed for any genetic abnormalities.
➡ The embryo is implanted into the mother's uterus only if it is healthy and free of
genetic defects/errors.

9. PREIMPLANTATION GENETIC DIAGNOSIS (PGD/PIGD)

10. PRENATAL DIAGNOSTIC GENETIC ANALYSIS/TESTING
These tests are performed on the fetus or embryo before it is born to
detect changes in a fetus's genes or chromosomes.
The couples with an increased risk of having a baby with a genetic or
chromosomal disorder are usually offered this type of testing during
pregnancy.
Newborn and Child Screening: It is used to identify genetic
disorders just after birth, so that it can be treated early in life.

11. Indications for newborn and childhood genetic analysis
Newborn with:
>Major birth defects
> Unusual (dysmorphic) facial features
> Suspicion of a metabolic disorder (e.g. phenylketonuria)
>Positive newborn screening test
>Congenital hypothyroidism

12. > Suspected
 aneuploidy (e.g. features of Down syndrome
 > unbalanced autosome (e.g. Prader-Willi syndrome)
 > sex chromosomal abnormality (e.g. Turner syndrome)
 fragile-X syndrome
Child with:
 Developmental delay and/or unexplained mental retardation
 Unusually tall or short stature, or growth delays
 Known chromosomal abnormality

13. • PRENATAL DIAGNOSTIC GENETIC ANALYSIS/TESTING
➤ Screening Tests in Adult
• Indications are: Adult-onset conditions, e.g. hemochromatosis, hearing
loss, visual impairment.
➤Screening for carriers of recessive genetic diseases, e.g. thalassemia,
Tay-Sachs disease, cystic fibrosis
➤ Mental retardation without a known cause.
➤Unexplained infertility or multiple pregnancy losses.

14. ➤Family history of cancer
➤ Screening of individuals with a personal or family history of cancer with a
known or suspected inherited predisposition.
For example BRCA1 and BRCA2 gene for breast cancer detection. The
others include colon cancer, ovarian cancer, retinoblastoma (embryonic
tumor of retina in the eye).
➤Family members of patients affected by cancer and who developed
cancer at an unusually young age with an unusual type of cancer.

15. • OTHER USES OF GENETIC TESTS
➤Forensic/identity testing: To identify an individual for legal purposes
such as to identify the crime or victims, a crime suspect, or establish
biological relationships between people (e.g., paternity dispute).
➤Research testing: Research testing is done to find unknown genes,
learn how genes work and advance our understanding of genetic
conditions.
➤Pharmacogenomics: The genetic testing can determine the
influence of genetic variation on drug response.

17. PRENATAL DIAGNOSIS OF GENETIC TESTING
> Various prenatal tests are generally done between 10 and 20 weeks of pregnancy.
> Waiting for the results of the prenatal tests is stressful for couples.
> These couples must be supported during this time and given full explanation of
results as soon as possible.
>If the prenatal tests detect an abnormality, it requires teams consisting of
obstetricians, midwives, radiologists, neonatologists, pediatric surgeons, clinical
geneticists and counselors, to provide integrated services for couples.
>Many ethical issues exist, including deciding what to do if the child is found to have
an incurable, life-altering genetic condition.

18. REASONS FOR PRE-NATAL TESTING AND DIAGNOSIS OF GENETIC
DISEASES
> If the fetus is affected, then it allows timely medical or surgical treatment
of a genetic condition before or after birth.
>If a fetus with disability is detected, it gives the parents the chance to
"prepare" psychologically, socially, financially and medically.
>Prenatal testing can lessen a couple's uncertainty. One of the options
after an abnormal result on prenatal testing may be to terminate the
pregnancy.
> It should be done only with the permission of parents. During this, the
couples may need counseling and psychological support.

19. INDICATIONS FOR PRE-NATAL GENETIC ANALYSIS
* A mother of advanced age (>35 years) who has increased risk of trisomy’s
* A parent
> Already having a child with a chromosomal abnormality or birth defect or
family history of birth defects
> who is a carrier of a translocation (balanced reciprocal or Robertsonian) or
inversion
> who is a carrier of an X-linked genetic disorder

20. Family History of
Chromosomal abnormality
> Single-gene disorder
> Neural tube defects
> Congenital structural abnormalities
> Mental retardation

21. * A fetus with abnormalities detected by ultrasound
* A genetic disorder for which there is no satisfactory treatment
* Abnormal levels of AFP, BHCG, and estriol performed as quadruplet
/triple test
* Parental consanguinity
*Recurrent spontaneous abortions/miscarriages
*Previous unexplained stillbirth
*Intake of certain medications or teratogens during pregnancy
*Maternal conditions such as diabetes, epilepsy, or alcoholism

22. METHODS FOR PRENATAL
DIAGNOSIS

23. METHOD
1.Preimplantation genetic
diagnosis
2.Ultrasonography
3.Amniocentesis
• Procedure risk 0.5-1.0%
• Performed in second
trimester (15-20 weeks)
4.Chorionic villus sampling
(CVS) performed during 9-11
weeks
USE
Identify genetic abnormalities before
implantation
> Determine fetal age
> Assess growth of fetus
> Detection of birth defects/structural abnormalities
> Sex determination (It is prohibited by law to reveal
the sex to couples).
➤ Amniotic fluid: Biochemical analysis to analyze
proteins & measure enzymes
> Cells of fetal origin for chromosomal analysis
➤ Fetal cells: DNA analysis, Chromosomal Analysis
RISK
Requires IVF
Protocol
None
Less than 0.5%
risk of
miscarriage
Less than 2% risk
of miscarriage

24. 5.Umbilical vein blood
sampling
(Cordocentesis)
Procedure risk 1-2%
Performed in the first
trimester
Specialized technique
6.Fetoscopy
> Fetal blood cells for
chromosomal analysis and
DNA analysis
> Fetal blood serum:
Measure serum enzymes and
proteins
To visualize the fetus in
utero
Less than 2% risk of miscarriage
Risk of miscarriage

25. AMNIOCENTESIS

27. ULTRASONOGRAPHY

28. CORDOCENTESIS

29. FETOSCOPY