GENETIC TESTING BASIS OF GENETIC

DISORDER, PRESYMPTOMATIC AND PRE-

DISPOSITION TESTING AND
PRENATNAL DIAGNOSIS AND SCREENING
SUBMITTED TO :- MRS ANUGRAH MILTON
( ASST. PROF.)
SUBMITTED BY :- MS MANSI
( MSC NURSING PREV.)
 OBJECTIVES
 GENETIC TESTING  PRESYMPTOMATIC AND
• Introduction PREDISPOSITION TESTING
• Definition
• Definition • Protocol
• Purposes • Components
• Uses • Types
• Indications • Examples
 PRENATAL DIAGNOSIS AND
• Types
SCREENING
• How genetic testing is done ? • Invasive
 COMMON GENETIC DISORDERS • Noninvasive
• Introduction
• Causes
• Trisomy 13,21 and 18
• Turner syndrome
 INTRODUCTION OF GENETIC TESTING

 
The analysis of human DNA in any of its forms or related products (chromosomes, RNA, proteins).
Genetic testing identifies changes in chromosomes, genes/DNA, or proteins. Genetic testing in a broader sense
includes tests for the possible presence of genetic disease, or mutant form of genes associated with increased
risk of developing genetic disorders.
It is a type of medical/genetic test that identifies changes in chromosomes, genes or proteins. Genetic tests
examine a person's DNA in a variety of ways. It looks for abnormalities in DNA taken from a person's blood,
body fluids or tissues. The results of a genetic test can confirm a suspected genetic condition that determine a
person's chance of developing or passing on a genetic disorder. More than 1,000 genetic tests are currently in
use. There are several methods which can be used for genetic testing:
Molecular Genetic Tests: It is single genes or short lengths of
DNA to identify variations or mutations that lead to a genetic
disorder.

Chromosomal Genetic Tests: It analyses whole chromosomes or

long lengths of DNA to see if there are large genetic changes,
such as an extra copy of a chromosome, that cause a genetic
condition.

Biochemical Genetic Tests: In this test, the amount or activity

level of proteins, i.e., abnormalities that indicate changes to the
DNA the result in a genetic disorder.
DEFINITION OF GENETIC
TESTING
 It is defined as examining a sample blood or other

1 body fluids or tissue for biochemical chromosomal or

get markers that indicate the presence absence of
genetic disease.

 It is also defined as type of medical test identifies

2 changes in chromosome genes or proteins.

 A genetic testing is analyzing a DNA look for genetic

3 alteration that may indicate an increased risk for

developing a specific disease or disorder.

( DR. VIJAY KUMAR GAUTTAM)

 PURPOSES OF GENETIC TESTING
To find genetic disease in an unborn child.

To screen embryos for disease.

To find out if people carry genes for a disease and might pass it on to their children.

To test for genetic disease in the adult before they cause symptoms,

To make a diagnosis in the person who has disease symptoms.

To figure out the type or dose of a medicine that is best for a certain person.

To determine a child's potentiality or person ancestry.

 USES OF GENETIC TESTING
Genetic testing can provide information about a person's genetic background.
The uses of genetic testing include.

USES OF GENETIC
Newborn
screening

TESTING
Diagnostic
testing

Carrier testing
CONT…
Prenatal testing

CONT..
Preimplantation testing

Predictive and
presymptomatic testing

Forensic testing
 INDICATIONS FOR MAKING GENETIC REFERRAL
Following conditions require a genetic referral ;-

Maternal Risk Factors

Prenatal Risk Factors

Pediatric Conditions

Mental Retardation
 TYPES OF GENETIC TESTING
Broadly there are two main categories of genetic tests:
Tests for mutations that affect all cells in
CONSTITUTION the body, and he been there since
conception
AL

Tests for changes that affect only certain

cells or cell types in the body and that
ACQUIRED occurred later in Genetic Tests for
constitutional mutations.
 GENETIC TESTS FOR CONSTITUTIONAL MUTATIONS

I. Analysis of DNA sequence • Karyotype to examine I.Analyzes the quantity of a

Molecular tests:

Cytogeneses Test :

Biochemical Test :
in patient with a rare the chromosomal downstream product of a gene
inherited disease. (e.g., not looking directly at
complement of an the gene , or the chromosome )
 Muscle dystrophy including number, form, • Example : newborn
 Gene DMD and size of the screening.
 Clinical picture: - 1 in 3500 chromosomes,  Phenylketonuria
male birth
• Frequently used for o Inherited metabolic disorder
• Progressive muscle o If untreated, leads to mental
weakness starting in early children who present
with couple anomalies, retardation, seizures.
childhood. o Affects 1 in 20,000 newborns
• Wheelchair by age of 12 developmental delay,
• Missing enzymes:-
yrs. and autism. phenylalanine hydroxylase.
• Death in 20s.
 HOW IS GENETIC TESTING DONE?
Once a person decides to proceed with genetic testing, a health care provider can arrange
testing. Genetic testing is often done as part of a genetic consultation. Genetic tests are
performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus
during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a
small brush or cotton swab to collect a sample of cells from the inside surface of the cheek.
The sample is sent to a laboratory where technicians look for specific changes in
chromosomes, DNA, or proteins, depending on the suspected disorder.

The laboratory reports the test results in writing to a person's doctor or genetic counselor,
or directly to the patient if requested. Newborn screening tests are done on a small blood
sample, which is taken by pricking the baby's heel. Unlike other types of genetic testing, a
parent will usually only receive the result if it is positive. If the test result is positive,
additional testing is needed to determine whether the baby has a genetic disorder.
Cont.…
Before a person has a genetic test, it is important to understand the testing
procedure, the benefits and limitations of the test, and the possible
consequences of the test results. The process of educating a person about the
test and obtaining permission is called informed consent. Individuals
interested in direct-to-consumer genetic testing do not need to go through a
health care provider to obtain a test, but they can get it directly from the
testing company.

After undergoing direct-to-consumer genetic testing, people who test positive

for a condition or are found to be at higher risk of developing a disorder are
encouraged to follow-up with a genetic counselor or other health care
provider.
 GENETIC DISORDERS

INTRODUCTION
Genetic diseases make-up a large proportion of the total disease burden in both pediatric and
adult populations. This proportion will continue to grow as our understanding of the genetic
basis of disease grows. In addition, modern medicine is placing increasing emphasis on the
importance of prevention. Because genetics provides a basis for understanding the fundamental
biological make-up of the organism, it naturally leads to a better understanding of the disease
process. In many cases knowledge can lead to actual prevention of the disorder. It also leads to
more effective disease treatment.
 GENETIC DISORDERS
A genetic disorder is a disease caused by a different form of a gene called
a variation, or an alteration of a gene called a mutation. Many diseases
have a genetic aspect. Some, including many cancers, are caused by a
mutation in a gene or group of genes in a person's cells. These mutations
can occur randomly or because of an environmental exposure such as
cigarette smoke.

Other genetic disorders are inherited. A mutated gene is passed down

through a family and each generation of children can inherit the gene that
causes the disease. Still other genetic disorders are due to problems with
the number of packages of genes called chromosomes. In Down syndrome,
for example, there is an extra copy of chromosome 21.
 CAUSES OF GENETIC DISORDERS IN
HUMANS
Genetic diseases in humans are caused due to abnormalities in genes or chromosomes. Such defects
can be caused by the following mechanisms:

Mutations: These are sudden inheritable Deletions: Loss of a part of chromosome as

changes in the nucleotide sequence of a gene. in the case of Jacobsen syndrome.

Aneuploidy: Aneuploidy is caused when

there are abnormal numbers of chromosomes
in an organism. This could be due to loss of a
chromosome (monosomy) or presence of
extra copy of a chromosome (trisomy,
tetrasomy, etc.)
 Inversions: Inversion of the nucleotide
Duplications: Duplication of a portion of
sequence because a portion of chromosome
chromosome that results in extra amount of
has broken off, got inverted and reattached at
genetic material.
the original location of the chromosome.

Translocations: When a portion of chromosome has got

transferred onto some other chromosomes. Sometimes
translocation can take place between two chromosomes, in
which case they interchange chromosome segments.
However, in some cases a portion of a chromosome may
simply get attached to another chromosome.
 Types of Genetic Disorders in Humans
Autosomal • These disorders are caused when an individual has inherited the
defective gene from a single parent. This defective gene belongs to
dominant genetic an autosome. Such an inheritance is also known as autosomal
disorders: dominant pattern of inheritance.

Autosomal recessive • Such disorders manifest only when an individual has got two
defective alleles of the same gene, one from each parent. These
genetic disorders genetic disorders are inherited via the autosomal recessive pattern
of inheritance.

• These are disorders caused by mutations in genes on the X chromosome.

Females are more frequently affected than males, and the chance of passing
on X-linked dominant disorders differs between men and women. Families
X-linked dominant: with an X-linked dominant disorder often have both affected males and
affected females in each generation. A striking characteristic of X-linked
inheritance is that fathers cannot pass X-linked traits to their sons (no male-
to-male transmission).
 • These are caused by mutations in genes on the X
chromosomes. Males are frequently affected than

X-linked
females, and the chance of passing on the disorder
differs between men and women. Families with an X-
linked recessive disorder often have affected males, but

recessive: rarely affected females, in each generation. A striking

characteristic of X-linked inheritance is that fathers
cannot pass X-linked traits to their sons (no male-to-
male transmission).

Multi- • Such disorders are the result of

genetic as well as
factorial environmental factors.
genetic
disorders:
 COMMON GENETIC DISORDERS IN
HUMANS
• This condition derives its name from Dr Langdon

DOWN Down, who described it in the Clinical Lecture

Reports of the London Hospital in 1866. The
chromosomal basis of Down syndrome was not

SYNDRO
established until 1959 by Lejeune and his colleagues
in Paris. It is also known as Mongolism or Trisomy
21 chromosome. One of the commonest genetic

ME
disorders, affecting 1 in 800 live births. It is a
chromosomal condition related to chromosome 21.
Most cases of down syndrome result from trisomy
21, means each cell in the body has three copies of

(TRISOM chromosome 21 instead of the usual two copies. The

extra genetic material disrupts the normal course of
development causing characteristic features of Down

Y 21)
syndrome.
08/23/2023 PRESENTATION TITLE 21
 • Hypotonic: At birth (80%), low IQ,
developmental delay
• Neurologic: Hypotonic, premature
senility. Alzheimer's onset in 10's
• Facies Flat occiput, microcephaly,

Clinical small mandible and maxillae, up

slanting palpebral fissures, epicanthal
folds, Brush field's

Features • spots in iris

• ENT: Furrowed prominent tongue,
high arched palate, ear anomalies,
frequent acute otitis media
• CVS 40% have congenital cardiac
defects, particularly endocardial
cushion defects
 • GL Duodenal, anal atresia and TE
fistula
• MSK: Lax joints including
dysplastic hips, vertebral

Clinical
anomalies, atlantoaxial instability
• Skin: Simian (palmar) crease,
abnormal dermatoglyphics

features
• Hematologic: Leukemias (1%
lifetime risk)
• Endocrine: Hypothyroidism
• Prognosis: Shorter life expectancy.
TRISOMY • Trisomy 13 (also called Patau syndrome) is a
genetic disorder in which a person has three copies
of genetic material from chromosome 13, instead

13 of the usual two copies. Rarely, the extra material

may be attached to another chromosome
(translocation).

• Trisomy 13 occurs when extra DNA from

chromosome 13 appears in some or all of the
body's cells. Trisomy 13 occurs in about 1 out of
Causes every 10,000 newborns. Most cases are not passed
down through families (inherited). Instead, the
events that to Trisomy 13 occur in either the sperm
or the egg that forms the fetus.
08/23/2023 PRESENTATION TITLE 25
 Cleft lip or palate

SYMPTOMS
Clenched hands (with outer
fingers on top of the inner
fingers)

Hole, split, or cleft in the

iris (coloboma)

Close-set eyes may

actually fuse together into
one

Low-set ears
CONT… Mental retardation,
severe

Decreased muscle

SYMPTOMS
tone

Small lower jaw

Undescended
testicle

small eyes

Extra fingers or
toes (polydactyly)
 EXAMS AND TESTS
The infant may have a single umbilical artery at birth. There are often signs of congenital heart disease, such as
abnormal placement of the heart toward the right side of the chest instead of the left.

Atrial septal defect

Patent ductus arteriosus

Ventricular septal defect

Gastrointestinal X-rays or ultrasound may show rotation of the internal organs

Chromosome studies show trisomy 13, or partial trisomy.

MRI or CT scans of the head may reveal a problem with the structure of the brain.
 TREATMENT

Treatment of children with Trisomy 13

is planned on a case-by-case basis. The
type of treatment given depends on the
patient’s individual condition.
TRISOMY 18
It is a genetic disorder in which a
person has a third copy of genetic
material from chromosomes 18,
instead of the usual 2 copies.
08/23/2023 PRESENTATION TITLE 31
Cause: - Presence of extra material
from chromosome 18. the extra
material interferes with normal
development.
 Crossed legs.

Clenched hands

Sign symptoms
Low birth weight.

Mental deficiency

Small jaw

Underdeveloped
fingernails
Unusual shape of
chest.
 EXAMS AND TESTS

Examination of the pregnant woman may show an unusually large uterus and extra
amniotic fluid. An unusually small place may be seen when the baby is born.
Physical examination of the infant may show unusual fingerprint patterns. X-rays may
show a short breast bone. Chromos studies show trisomy 18, partial trisomy, or
translocation.
 Hole, split, or cleft in the iris

Separation between the left and right side

OTHER of the rectus abdominis muscle Umbilical
hernia or inguinal hernia.

SIGNS
INCLUDE There are often signs of congenital heart
disease, such as
Atrial septal defect (ASD) Patent ductus
arteriosus (PDA)
Ventricular septal defect (VSD).
TESTS MAY ALSO SHOW
KIDNEY PROBLEMS,
INCLUDING:
Horseshoe kidney
Hydronephrosis
Polycystic kidney.
Treatment
Treatment of children with Trisomy 18 is
planned on a case-by-case basis. Which
treatments are used depends on the
patient's individual condition.
TURNER SYNDROME (SEX
CHROMOSOME DISORDER IN
FEMALES)
Turner syndrome is a genetic disorder in
girls caused by a missing or defective X
(female) chromosome. It occurs in 1 of
2,000- 2,500 live female births.
08/23/2023 PRESENTATION TITLE 39
 Short Stature

Factions In
Childhood

Symptoms
Hearing Disorders

Failure Of Ovaries

Lower Jaw Smaller

Than Normal

Drooping Eyelids
Webbed Neck

Heart Defect
Diagnosis
Done by chromosomal analysis.
Finding of the specific chromosomes
problem of the syndrome is the only
definitive diagnosis.
 TREATMENT
There are two main medications given to girls with Turner syndrome. One is human
growth hormone, used to increase the girl's Treatment growth rate and help her be
taller. The other medication is estrogen, a female hormone, to replace the estrogen
which would normally have been produced by the ovaries. Another female hormone,
progesterone, is also given when the girl grows older, to grows up. However, some
women with Turner syndrome can use in vitro fertilization to become pregnant, using
donated eggs. Since a girl with Turner syndrome usually does not have ovaries, she
cannot produce eggs and become pregnant when she help her have a normal monthly
menstrual cycle. Other women choose to adopt children in order to have a family.
 SOME OTHER GENETIC DISORDERS ARE ;-
Phenylketonuria
Familial hypercholesterolemia
Sickle cell anemia

Cystic fibrosis
Hemophilia
Thalassemia
Celiac disease
PRESYMPTOMATIC
AND
PREDISPOSITION
TESTING
It is testing also known as predictive testing e.g., BRACA1 , has a 65% cumulative risk for
breast cancer .

Predictive and presymptomatic testing are used to detect gene mutation associated with
disorders that appears after later in life.

Presymptomatic testing can determine whether a person will develop a genetic disorder ,
such as hereditary hemochromatosis ( an iron overload disorder).

Predisposition testing (i.e., genetic testing that provide information about a person
susceptibility to disease .)

A genetic predisposition ( sometimes also called genetic susceptibility is an increased

likelihood of developing a particular disease based on a persons genetic makeup.
 AVAILABILITY OF PREDICITIVE
TESTING
Cystic fibrosis

Tay sachs disease

Huntington’s disease

Breast cancer

Colon cancer

Thyroid cancer
 DEFINITIONS

Presymptomatic Testing: Positive tests results show that you will

develop symptoms of a disease. For example, this type of test is
used to check for mutations linked to Huntington’s Disease.

Predispositional Testing: Positive tests results show that you are

more likely than others to develop symptoms of a disease. But
doctors cannot know for sure if you will get sick. For example,
this type of test is used to check for mutations linked to breast 
cancer.
  Two face to face visits for people
requesting genetic testing.
o First visit- meet with genetic
counselor and receive a
PRESYMPTOMATI psychological/psychiatric
C TESTING evaluation.
PROTOCOL o Second visit- results declaration
o Referral as needed/post test follow
up.
COMPONENTS OF PRESYMPTOMATIC TESTING
PROTOCOL
1.INITIAL TELEPHONE CONTACT
 Explain the genetic testing process.
 Provide the basic information ( cost and timing ).
 Review considerations with instruction with insurances and health plans.

2. GENETIC COUNSELLING
 Review family history
 Explanation of the risk
 Review risks, benefits and limitations of the test.
 Basic understanding of patients experience and perception of HD.
3. DOCUMENTAION OF INFORMED CONSENT.

4. COORDINATION OF SAMPLE COLLECTION.

5. PSYCHOLOGICAL ASSESSMENT.
 Assessment Is not an obstacle to testing.
 Helps identity those who may need greater emotional support during and after
testing.

6. REVIEW OF THE POTENITAL IMPACT OF THE TEST.

 Negative and positives
 Family planning
 Financial planning.
 Changing relationship.
7.DISCLOSURE OF RESULTS.

8. FOLLOW UP AFTER TESTING

a) Individualized to respond to the needs of the patient.

b) Baseline neurological examination should be encouraged for positive individual.

C) Additional visits/ referrals for supportive counselling should be offered as needed.

 PREDISPOSITION TESTING

Predispositional Testing: Positive tests

results show that you are more likely than
others to develop symptoms of a disease. But
doctors cannot know for sure if you will get
sick. For example, this type of test is used to
check for mutations linked to breast cancer.
Genetic predisposition testing is a type of genetic testing that helps to identify risks for
diseases. It looks at an individual’s unique DNA sequence, which can indicate if they
have a higher risk or likelihood of developing certain conditions in the future. This type
of testing can be beneficial as it allows individuals to take proactive measures to protect
their health and well-being.

In essence, genetic predisposition tests provide information about how likely someone
may be to develop a specific disease based on their genes. This knowledge can help
people make informed decisions regarding lifestyle changes or preventive care such as
diet, exercise, medications, etc., that could reduce their chances of getting ill in the
future.

Additionally, this type of testing gives insight into potential inherited traits that could
influence the course of treatment should someone develop an illness later on down the
line. With all this in mind, it’s clear why many are turning towards genetic predisposition
testing when seeking answers about their overall health and wellbeing. Transitioning now
to look at what types of tests are available.
 TYPES OF TESTS AVAILABLE
Genetic predisposition testing looks at an individual’s genes to identify any potential risks for
developing certain diseases. Genetic tests can provide valuable information about a person’s
hereditary health risk and help them make informed decisions on how to manage their
personal health. There are several types of tests available that look for genetic markers,
mutations, or variations associated with particular hereditary diseases.

The most commonly used type of test is the single gene mutation analysis. This involves
looking for specific changes in a person’s DNA sequence that may be linked to an inherited
disorder or trait. In addition, there are also tests which use whole-genome sequencing
technology to screen for rare variants across many different genes associated with various
conditions.
Some of these tests include
 chromosomal microarray analysis (CMA),
quantitative fluorescent polymerase chain reaction
(QF-PCR), and array comparative genomic
hybridization (aCGH). By using this
comprehensive approach, it allows doctors to
detect multiple genetic variations within a single
sample.
 How Predisposition Works

Genetic predisposition comes from genetic variations that

are passed down from parent to child. These variations are
somehow different from what’s considered the “standard”
gene that most people have, and they leave you vulnerable
to disease if you encounter the right set of contributing
factors at some point in your life.
 PRENATAL TESTING AND DIAGNOSIS

Prenatal testing and diagnosis prenatal genetic testing

generally refer to tests that are done during pregnancy
to either screen for or diagnose a birth defect.
 PURPOSES

To enable timely, medical or surgical treatment of a condition

before or after birth

To give the parents a chance to abort a fetus with the diagnosed

condition

To give parents a chance to prepare for a baby with a health

problem or disability or for the likelihood of a stillbirth.
Prenatal Screening
 Screening for potential for neonatal infection
 Screening for hemolytic disease of new born
 Screening for sickle cell and thalassemia
 Down’s syndrome screening
 Fetal anomaly screening
 Abdominal palpation and measurement of
symphysis-fundal distance
 TYPES OF PRENATAL TESTING AND SCREENING

It is performed to detect any genetic abnormality in the fetus. This type

of testing is suggested to couples who are known or have a previous
baby with a genetic or chromosomal disorder. The testing will help them
to decide whether to abort pregnancy. Prenatal test can be categorized as
invasive and noninvasive. Noninvasive sampling includes obstetric
ultrasound and fetal echo cardiograms. Invasive studies includes
maternal serum alpha-fetoprotein (AFP), amniocentesis , chorionic
villus sampling, Percutaneous umbilical Cord Blood Sampling (PUBS),
fetoscopy and fetal time sampling. The purpose and brief description of
each is as below: There are two types of prenatal diagnosis and testing:
I. Non-Invasive Techniques:
• 1. Fetal Visualization:
• (a) Ultrasound
• (b) Foetal echocardiography
• (c) Magnetic resonance imaging (MRI)
• (d) Radiograph
• 2. Screening for Neural Tube Defects (NTDs)
• 3. Screening for Fetal Down Syndrome
• 4. Separation of Fetal Cells from the Mother's Blood.
II. Invasive Technique:
1.Fetal Visualization: Embryoscopy and Fetoscopy
2.Fetal Time Sampling
• (a) Amniocentesis
• (b) Chorionic villus sampling
• (c) Percutaneous umbilical blood sampling (PUBS).
• (d) Percutaneous skin biopsy.
• (e) Other organ biopsies, including muscle and liver biopsy.
• 3. Preimplantation biopsy of blastocysts obtained by in vitro
fertilization.
• 4. Cytogenetics E. Molecular Genetics.
 NONINVASIVE PRENATAL TESTING
ULTRASOUND
Ultrasound has become the standard in fetal evaluation because it is safe and noninvasive. It
confirms pregnancy, determines fetal age, growth and development, identifies placental
implantation site, determines fetal viability or death, confirms multiple gestation, identifies masses
associated with pregnancy, assesses amniotic fluid volume and placental calcification, and
facilitates the use of more invasive studies, diagnostics, and treatment. When assessing for specific
congenital anomalies or abnormalities in early pregnancy, the uterus and bladder must be
differentiated. To facilitate this, clients are instructed to consume approximately 32 to 48 oz of fluid
1 to 2 hours before the procedure and are encouraged not to void until the procedure is completed.
Some discomfort due to the pressure exerted by transducer over the bladder is expected. A full
bladder is typically not necessary for clients in the late stages of pregnancy.
08/23/2023 PRESENTATION TITLE 64
 FETAL ECHOCARDIOGRAMS

Fetal echocardiograms are performed through the maternal

abdomen when there is suspicion of a congenital cardiac defect.
This procedure provides information regarding blood flow
velocity and the direction, size, position, valves, and chambers of
the heart. No specific patient preparation is necessary and no
discomfort is involved in the procedure. Client preparation and
counseling regarding expected and actual study findings and
emotional support to assuage and anxiety about the procedure are
necessary.
08/23/2023 PRESENTATION TITLE 66
 SCREENING FOR NEURAL TUBE

In the condition of an open NTD (e.g. anencephaly, spina bifida) and

abdominal wall defects in the fetus can be detected. Also, a NTD can
be distinguished from other fetal defects, such as abdominal wall
defects, by the use of an acetylcholinesterase test carried our on
amniotic fluid. If the level of acetylcholinesterase rises along with
AFAFP, suspected as a condition of a NTD. Screening for NTDs is
recommended if the following are present:
08/23/2023 PRESENTATION TITLE 68
CONT…
 Ultrasound findings indicate NTDs.
 A child with NTDs is already in the family.
 A family history of NTDs exists. especially a mother with NTDs.
 The mother has type I diabetes mellitus during pregnancy.
 Maternal exposure to drugs, such valproic acid, is associated with
NTDs.
 The developing fetus has 2 major blood proteins, albumin and alpha-
fetoprotein (AFP), while adults have only albumin in their blood.
 SCREENING FOR FOETAL DOWN SYNDROME-

help assess the baby's chances Screening rests of having this kind
of down syndrome. The can help decide whether to have a
diagnostic testing to find out for sure about the baby's condition.
Screening tests tell how likely it is that the may have & condition,
but only a diagnostic test like amniocentesis can tell whether the
baby actually has the condition. Also screening tests carry no risk
for the mom or baby; diagnostic tests carry a small risk of
miscarriage.
SEPARATION OF FOETAL CELLS FROM THE
MOTHER'S BLOOD

Fetal blood cells enter maternal circulation ugh the

placental villi. These cells can be and safely from
approximately 12-18 weeks' of gestion onward. Fetal
blood cells can then be sed for the diagnosis of genetic
disorders FISH, PCR etc. Fetal cells separated mother's
blood have been successfully the diagnosis of cystic
fibrosis, sickle cell anemia and thalassemia in a fetus.
 INVASIVE PRENATAL TESTING
Serum alpha-fetoprotein (AFP) and triple screens: Maternal serum AFP
screening is used routinely to assess for neural tube defects. AFP screening
involves obtaining a venous sample of maternal blood. Anencephaly is to occur
once in every 8000 births and spina bifida once in every 2000 births, with only
5 to 10 percent of these occurrences in families with a previous history of neural
tube defects. Screenings are usually performed between 16 and 18 weeks'
gestation. Elevated AFP levels may be indicative of neural tube defects,
multiple gestation, Rh incompatibility or isoimmunization, low gestational age,
or other congenital anomalies such as congenital nephrosis, duodenal atresia,
esophageal atresia, tetralogy of Fallot, or hydrocephaly Low AFP levels may be
indicative of trisomy 13,18 and 21.
The determination of AFP levels is also done in conjunction with
triple marker screening. This consists of testing for AFP, human
chorionic gonadotropin and serum estriol levels. Triple marker
screening especially useful in testing for trisomy’s. Depending on
the results of either of these studies, other studies may be
recommended. Sensitive counseling, education and support by
nurses, especially trained in this field can help clients make
informed decisions regarding the tests, their outcomes, and any
additional steps that may be needed.
Amniocentesis and chorionic villus sampling: Two prenatal
screening tests are used to assess fetal karyotype (the actual picture
of the fetus' chromosomes) abnormalities:
1. Amniocentesis
2. Chorionic villus sampling (CVS).
Both tests are used to diagnose trisomies 13,
18, and 21 and the neural tube defects. They
also assess abnormal AFP levels, glucose
levels, and other substances found in the
amniotic fluid or fetal tissue.
 AMNIOCENTESIS

Amniocentesis involves the insertion of a needle through the maternal abdominal and uterine
walls into the amniotic space. Approximately 20 to 30 mL of amniotic fluid is aspirated. The
procedure is performed under ultrasound guidance at approximately 16 to 20 weeks' gestation.
Fetal cells are retrieved for analysis. Results take approximately 10 to 28 days. Amniocentesis
is performed to evaluate further highs or low AFP results to detect hematologic disorders
(beta-thalassemia, and sickle cell anemia), chromosomal abnormalities, or sex-linked genetic
defects. It is preferred test for neural tube defects. Tay-Sachs disease, errors of metabolism,
and fetal infection. Sex also may be determined through this procedure; however, it is not
performed to satisfy simple fetal gender curiosity. Later in pregnancy, amniocentesis is used to
assess fetal lung maturity by the lecithin/sphingomyelin ratio.
08/23/2023 PRESENTATION TITLE 76
 INDICATIONS

Carriers of a metabolic or autosomal recessive disorder

A maternal age more than 35 years at the time of delivery

A family history of mental retardation

Teratogen exposure before or during the pregnancy and abnormal ultrasound or

AFP results.
 RISKS :-

Spontaneous abortion in approximately 1% of all cases

Nausea

Abdominal pain

Placental or umbilical cord perforation that leads to hemorrhage or isoimmunization and hematologic disease

Premature labor or rupture of membranes

Transvaginal leakage of amniotic fluid

Maternal or fetal infection.

 ROLE OF A NURSE

Before procedure, nurses must ascertain that informed

consent for the procedure is obtained
Reaffirm or clarify information that is questioned
If necessary, request that a genetic counselor, nurse
practitioner talk with the patient and significant others.
Provide emotional support before, during and after the
procedure.
 CHORIONIC VILLUS SAMPLING

Chorionic villus sampling is performed in the first trimester

between weeks 0 and 12 but mostly after 8 weeks' gestation. It
provides the earliest diagnosis of a fetal problem. Any candidate
for amniocentesis is generally a candidate for CVS. The procedure
is performed under ultrasound guidance, either transabdominally
or trans cervically depending on placental position. Any woman
with active type-1 genital herpes must undergo transabdominal
CVS, however.
08/23/2023 PRESENTATION TITLE 81
The test involves the removal, by genetic suction, of a sample of fetal tissue from villi of
chorion, actual fetal tissue that anchors the fetus to the uterine wall. Two advantages of CVS
over amniocentesis include its ability to be performed early in gestation and the direct
examination of fetal cells. Karyotyping by CVS can be a more expedient test for those
families who wish to make reproductive decisions. The procedure facilitates accurate
diagnosis of chromosomal, Mendelian, or single gene problems as well as metabolic or
hematologic problems. CVS is not recommended for the is immunized client because is
sensitization may be enhanced through this invasive procedure. In addition, CVS cannot
measure AFP levels and offers no information on neural tube defects associated disorders.
Some studies suggest that there is increased risk of fetal loss with CVS compared with
amniocentesis. When performed in centers in which CVS is routine, however, the fetal loss
rate is reported at approximately 19%. Limb reduction has been associated with CVS,
although the rate does not seem to exceed that found in the general population. All other
risk management and nursing care considerations mirror those with amniocentesis.
 PERCUTANEOUS UMBILICAL
BLOOD SAMPLING (PUBS)
Percutaneous Umbilical Blood Sampling (PUBS) permits the
removal of blood from the fetal-placental circulation.
Because it is less risky, it has replaced fetoscopy, and
virtually has revolutionized our ability to assess, evaluate,
and treat the fetus in utero by direct venous access. It can be
performed as early as 16 to 18 weeks' gestation or up to term
providing there is accurate cord visualization. Test results are
obtained in 48 to 72 hours.
08/23/2023 PRESENTATION TITLE 84
 PROCEDURE

The procedure entails passing a spinal needle

through the maternal abdomen and uterine wall into
umbilical blood vessels under high-resolution
ultrasound guidance. A blood sample is aspirated
into a heparinized syringe. The preferred testing
site is the placental-cord (cordocentesis). Fetal
abdominal cord and free loops of cord are also
acceptable.
 INDICATIONS

Fetal anemia
Severe red blood cell alloimmunization
Non-immune fetal hydrops
Erythroblastosis fetalis
Inherited disorders
Thrombocytopenia
Fetal infection
Evaluation of thyroid function
 EMBRYOSCOPY
It Is Performed In The First Trimester. In This Technique,
A Rigid Endoscope Is Inserted Via The Cervix In The
Space Between The Amnion And The Chorion, Under
Sterile Conditions And Ultrasound Guidance, To Visualize
The Embryo For The Diagnosis Of Structural
Malformations.
 FETOSCOPY

It is performed during the second trimester E (after 16 weeks' gestation). In

this technique, R a fine-caliber endoscope is inserted into the 22 amniotic
cavity through a small maternal abdominal incision, under sterile conditions
and ultrasound guidance, for the visualization of the embryo to detect the
presence of subtle structural abnormalities. It also is used for fetal blood and
tissue sampling.
 PERCUTANEOUS SKIN BIOPSY
These biopsies are taken under ultrasonic guidance
between 17-20 weeks' gestation, is prenatally
diagnosing serious skin disorder such as anhidrotic
ectodermal dysplasia, epidermolysis bullosa fetalis,
epidermolysis bullosa dystrophic, hypo hidrotic
ectodermal dysplasia, oculocutaneous albinism and
g forms of ichthyosis.
OTHER ORGAN BIOPSIES, INCLUDING MUSCLE
AND LIVER BIOPSY

Fetal liver biopsy is best performed between 17-20 weeks'

gestation under ultrasound guidance. Fetal liver biopsy is
needed n diagnose inborn errors of metabolism, such as
ornithine transcarbamylase deficiency, glucose-6-
phosphatase deficiency, glycogen storage disease type IA,
nonketotic hype glycemia and carbamoyl-phosphate
synthetase deficiency. In Fetal muscle biopsy, it is carried
under ultra sound guidance about 18 weeks to analyze the
muscle or diagnosis for muscular dystrophy.
 FETAL TISSUE SAMPLING
Another invasive type of testing involves fetal tissue sampling. Fetal tissue sampling is indicated
for disorders that are not diagnosable through amniocentesis or CVS and are at increased risk for
congenital anomalies. The procedure may be performed at 16 to 22 weeks' gestation, and fetal
skin, liver, or muscle tissue may be sampled. Skin specimens approximately 2 mm in diameter
typically are taken from the buttocks, back, thorax, and occasionally the scalp. In cases in which
potential liver enzyme abnormalities may exist and are not diagnosable by other means, liver
biopsy is indicated; however, few have been performed. A muscle biopsy might be indicated
when DNA analysis is inconclusive or carrier status cannot be ascertained and there is a risk for
such conditions as the X-linked recessive Duchenne muscular dystrophy. Becker's muscular
dystrophy, or mitochondrial myopathies; few have been performed to date. Fetal tissue sampling
is performed under the guidance of ultrasound with the client mildly sedated in order to decrease
fetal movement.
 RISKS
Spontaneous abortion

Spontaneous abortion

Amniotic fluid leakage Maternal or fetal infection or injuries

Preterm labor or delivery

Hemorrhage due to anterior abdominal wall, uterine or placental injuries.

 NEWBORN SCREENING
In some countries like USA, there is routine testing of
infants for certain genetic disorders such as
phenylketonuria, congenital hypothyroidism, sickle cell
anemia, congenital adrenal hyperplasia, galactosemia,
biotinidase deficiency, maple syrup urine disease, etc. Such
genetic disorders can be treated early in life. Some of the
conditions that a neonatal nurse is most likely to encounter
in practice are as follows:
 Errors in Metabolism
Each of the metabolic disorders is associated with some
disruption in the normal metabolic pathway in the neonate,
either due to a defective gene or enzyme deficiency.
Sometimes the target cells may not be receptive to the
metabolic action of the specific enzyme. Most common
examples, generally autosomal recessive, include
Phenylketonuria (PKU), congenital hypothyroidism, syrup
urine disease, and galactosemia. Phenylketonuria is a
blockage of the conversion of phenylalanine to tyrosine. It
frequency in population is 1:11000 live births.
 INTERPRETING THE RESULTS
OF A GENETIC TEST
The results of a genetic test are not easy to interpret and
explain without knowledge of proper genetic
background. Therefore, patients and their families must
ask questions about potential meaning of genetic test
results before and after the test is performed, Genetic or
medical experts consider a person's medical history,
family history, and the type of genetic test when
interpreting its results.
positive test result may also have implications for certain blood relatives of the person
undergoing testing, and may also require their screening for the same genetic
condition.

A positive result of a predictive or Presymptomatic genetic test usually cannot

establish the exact risk of developing a disease and the course or severity of a
condition cannot be predicted. A negative result can indicate that a person is not
affected by a particular disorder, is not a carrier of the abnormal gene, or does not
have the increased risk of developing the disease. There is possibility of a false
negative result. Further testing maybe required to confirm a negative test.
LEGAL ISSUES IN
GENETIC TESTING
• Genetic testing holds keys to human
health but is also fraught with legal
issues.
 With the advent and advancement of genetic testing, hope for better medical care emerged.
However, legal issues concerning genetic testing also demanded attention. These issues include
how and when genetic testing should take place, what kinds of consent a human subject should be
entitled to and who should have access to genetic material and data derived from testing. Initially,
the Department of Health and Human Services Human Subjects Protocol stood as the sole
legislation applicable to etic testing. Today, the Health Insurance Portability and Accountability Act
and the Genetic Information Nondiscrimination Act seek to settle these issues.

Protection of human

Health insurance portability and accountability act

Genetic information non discrimination act .

 ETHICAL AND LEGAL ISSUES IN
GENETIC DIAGNOSIS AND TESTING
Consent to Being Screened
• The patient needs to be informed about the implication of
genetic screening before they can provide informed
consent. The public view genetics with a sense of
inevitability. However, a genetic condition alone may
modify risks from environmental or life style factor. The
voluntary nature of the screening process must be
emphasized.
 COUNSELLING

It can reduce potential psychological distress; counselling should be

available to provide information about genetic risk and explain
choices regarding genetic testing and further management. Support is
needed for individuals who need to consider issue such as stigma dis-
closure to family members and confidentiality. Couples also known to
carry a recessive or dominance single gene defect or sex linked
condition needs counselling about their Situ Hybridization (FISH)
reproductive option. This may include prenatal diagnosis and possible
pregnancy termination in the case of an affected fetus and pre-
implantation genetic diagnosis.
 RISK OF STIGMA
The public understanding of genetic may
be limited and can lead to stigma
misunderstanding of the genetic risk of
developing disease can increase
stigmatization.
 CONFIDENTIALITY
Like other medical information, results from genetic testing are
considered confidential; under normal practice, the doctor-patient
relationship protects against disclosure of genetic information.
However, there is less clarity where relatives wish to know the
result of a family member's genetic test, as it may have direct
relevance for them. Another particular dilemma is the case of a
pregnant woman wanting to know the result of a test taken by the
baby's father. The storage of genetic screening data and registries
of patients creates particular concern, given that the results may
impact negatively on family members.
 DISCLOSURE TO FAMILY MEMBERS

Doctors face a dilemma when reporting the results of genetic screening.

Standard medical practice is based on the principles that doctor should focus
on their patient and that medical information should remain confidential. It
is unclear if doctors are ethically permitted to inform relatives in cases when
the result of a genetic test indicates real risk to their health Doctors may also
be faced with a decision about whether to persuade the patient about the
need to disclose their test result to relatives’ although most professional
bodies opinion that disclosure should not be against the right of relatives
have won priorities.
 BENEFITS OF GENETIC TESTING

IF NEGATIVE
Relief
Fewer Health Checkups And Tests That Go With Begin In A Family
That Tends To Have A Higher Risk Of A Particular Genetic
Disease.
IF POSITIVE
Able to make informed decisions
May be possible to reduce the risk of coming down with severe
symptoms.
 LIMITATION

Mutation may not always lead to disease

Existing tests only look for the most common mutations, some
disease-causing mutation will not be detected by conventional
tests.
Small chance of errors in testing procedure.
Testing is not always matched by treatment.
SUMMARY
Conclusion
 DNA is the hereditary material and any change in it leads
to mutation.
 Mutation leads to improve expression so cause disease.
 To explore whether an individual possess any disease or
not we do genetic testing.
 By this technique we analyze our DNA for sake of our
convenience to explore a disease and late steps to get rid
of that disease.
 RESEARCH
Genetic testing for Alzheimer's disease: trends, challenges and ethical
considerations

PMID: 31770136
Miguel E Rentería , Brittany L Mitchell , 
   
DOI: 10.1097/YCO.0000000000000573
Amaranta Manrique de Lara
2020 Mar;33(2):136-140.
Abstract
• Purpose of review: Advances in personal genomics have made predictive genetic
testing increasingly popular. The purpose of this review is to examine and summarize
recent literature regarding the ethical concerns and considerations surrounding genetic
testing for Alzheimer's disease.
• Recent findings: Four basic bioethical principles can be applied in the context of
genetic testing: autonomy, nonmaleficence, beneficence and justice. The concepts of
clinical validity, clinical utility and personal utility are also necessary for the ethical
deliberation of genetic testing for Alzheimer's disease. Ethical considerations can differ
among three distinct settings present in the literature: research, clinical and direct-to-
consumer services. Studies have found that the negative psychosocial impact of genetic
test results on the individual is limited, but emphasize the importance of pre/post testing
genetic counselling.
SUMMARY
• Summary: The literature should ideally inform policy-making
around genetic testing. There exists an urgent need for regulation,
particularly in the direct-to-consumer (DTC) market, since interest
for testing in this context is rapidly growing. Standardized
protocols for disclosure should be developed, and there is a need
to find ways to meet the growing need for genetic counselling.
Importantly, comprehensive, evidence-based regulation requires
that research be conducted in different contexts with more diverse
participants.
 BIBLIOGRAPHY
 Brar KN. Textbook of advanced nursing practice. 1st ed. New Delhi: Jaypee Brothers medical
publishers; 2015. P. 220-44.
 Gauttam V. Textbook of Advance nursing practice. 2nd ed. New Delhi: Kumar publishing house
Nursing books; 2022. P. 236-42.
 Konar H. Textbook of Obstetrics. 9th ed. New Delhi: Jaypee brothers medical publishers: 2019. P.
341-48.
 https://pubmed.ncbi.nlm.nih.gov/31770136/
 https://www.verywellhealth.com/genetic-predisposition-5087879
 https://health.ucdavis.edu/huntingtons/genetics-presymptom.html
Thank you