Genetic Counseling &

Prenatal Diagnosis
Dr. Dilip Choudhary
Moderator: Dr. D. Singh

1 02/03/2016
Genetic Counseling

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 Learning Objectives-
O 1. What is genetic counseling?

O 2. Why it is needed?

O 3. What are the clinical situations (indications)

where it is important?

O 4. Types of genetic counseling

O 5. What are the steps of genetic counseling?

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 Introduction:
O Genetic counseling is communicative process

which deals with human problems associated with

occurrence and or recurrence of a genetic disorder
in a family.

O An individual who seek genetic counselling is

known as a consultand.

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This involves an attempt by counsellor to help the
consultand to:
 Understand the medical facts including diagnosis,
probable course of disorder and available
management.
 Understand the mode of inheritance of the disorder
and the risk of developing and/or transmitting it.
 Understand the alternatives for dealing with the risk
of recurrence.
 Choose the course of action which is appropriate for
them.
 Make the best possible adjustment to the disorder in
an affected family member and or to the risk of
recurrence of the disorder.
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 Purpose of genetic counseling
 Provide concrete, accurate information about inherited
disorders.
 Reassure people who are concerned that their child may
inherit a particular disorder that the disorder will not
occur.
 Allow people who are affected by inherited disease to
make informed choice about future reproduction.
 Educate people about inherited disorder and the process of
inheritance.
 Offer support by skilled health care professionals to
people who are affected by genetic disorders.
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 Indications
1. Advanced parental age:-
Maternal age ≥35 yrs
Paternal age ≥50 yrs
2. Previous child with or family H/O:-
Congenital anomaly
Dysmorphism
Intellectual disability
Isolated birth defect
Metabolic disorder
Chromosomal abnormality
[Link] onset genetic disorder (presymptomatic testing):-
Cancer
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[Link]
[Link] exposure
[Link] pregnancy loss or infertility
[Link] screening abnormality
Maternal serum α-feto protein
Maternal triple or quad test
Fetal ultrasonography
Fetal karyotype
[Link] screening based on ethnic risk
Sickle cell anemia
Tay- sachs, Canavan, Gaucher disease
Thalassemia
[Link] up to abnormal neonatal genetic testing

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 Types of Genetic Counseling
Two types of genetic counseling:
(A) Prospective genetic counseling:
• This allows for the true prevention of disease.
• This requires to identify heterozygous individuals for
any particular defect by screening.
• Explaining to them the risk of their having affected
children if they marry another heterozygote for the
same gene.
• If heterozygous marriage can be prevented or
reduced, the prospects of giving birth to affected
children will diminish.
• Ex: Sickle cell anaemia
Thalassemia 02/03/20169
 (B) Retrospective genetic counseling:
• Most genetic counseling at present is retrospective,
(the hereditary disorder has already occurred within
the family).
• Ex. Mental retardation
Psychiatric illness
Inborn errors of metabolism
• The methods which could be suggested under
retrospective genetic counseling are:
Contraception
Pregnancy termination.
Sterilization
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 Areas of genetic counseling:
(A) Prenatal Genetic Counseling:
Several different reasons a person or couple may seek
prenatal genetic counseling. If a woman is of age 35 or
older and pregnant, then there is an increased chance that
her fetus may have a change in the number of chromosomes
present.

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(B) Pediatric Genetic Counseling:
Families or pediatricians seek genetic counseling when a
child has features of an inherited condition. Any child who
is born with more than one defect, mental retardation or
dysmorphic features has an increased chance of having a
genetic syndrome. A common type of mental retardation in
males for which genetic testing is available is fragile X-
syndrome.

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 Steps of genetic counseling
• Include present, past history, detailed family history, obstetric history
including still births and abortions if any and exposure to teratogen.
History & • Careful examination of affected( photographs, measurement) and of
Physical apparently unaffected individuals in the family.
examination

• Construct a 3 generation pedigree diagram with their age, sex and

state of health.
Pedigree

• One of the most important aspect, often called “recurrence risk”. Requires
to take into account- Mode of inheritance
Risk
Analysis of pedigree or family tree
assessment Results of various tests

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 • Most crucial step, confirm the diagnosis by available
Diagnosis
diagnostic tests.

• Transmitting the information, with ample time for

Communication
discussion and questions.

• Discuss available options for treatment of disease and

prevention of known complications or prevention of
Management genetic disorder( medical termination of pregnancy).

• Group of patient or parents of children with same

Support groups
disorder (patient support group)

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Prenatal diagnosis

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O Introduction: procedures which are used to detect
genetic disorders during early stages of pregnancy.

O Indications ;
1. To identify fetal disease when abortion is being
considered.
2. Direct fetal treatment

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 Methods of prenatal diagnosis
(a) Imaging- Ultrasound
Fetoscopy
MRI
(b) Fluid analysis- Amniocentesis
Cordocentesis
(c) Fetal tissue analysis- Chorionic villus sampling
(d) Maternal serum tests- α-feto protein
Triple test
Quad test
(e) Maternal cervix- Fetal fibronectin
Fluid
Bacterial culture 02/03/2016 17
Non invasive
methods Invasive methods

Imaging- Fluid analysis-

USG, MRI Amniocentesis,
Cordocentesis,

Maternal serum Fetal tissue analysis-

analysis
Chorionic villus
sampling

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 Imaging
Ultrasound–
O Real time USG can detect
• fetal growth abnormalities-
by biometric measurement of biparietal diameter,
femoral length, or head or abdominal circumference.
• Fetal anomalies eg. Hydrocephalus, NTDs, duodenal
atresia, diaphragmatic hernia, renal agenesis, limb
anomalies, omphalocele, gastroschisis, hydrops.
• Also help in performing BPP, cordocentesis and other
invasive procedures
O Doppler USG- for velocimetry and detection of increased
vascular resistence due to fetal hypoxia.

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 Fluid Analysis
Chorionic villous sampling
O Transvaginal or transabdominal
chorionic villous biopsy, which
provides fetal cells.
The placenta contains tissue
that is genetically identical to fetus.
O Timing: In first trimester,
shouldn’t be performed before 10wk,
commonly performed between
11 and 13 wks.
O Indications: for karyotype, enzyme assay, molecular DNA
genetic analysis.

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O Method of CVS: two ways to perform a CVS,
transabdominally (TA) and transcervically (TC),
depends on the location of the villi in the uterus.
Transabdominal approach-
When the villi are anterior,
under all aseptic precautions
ultrasound guided needle is
passed through abdominal
Wall and the uterus to reach
the villi. A syringe attached
to the needle is used to
suction out a small amount
of villi.
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Transcervical approach-
When the villi are in the lower part of the uterus and
posterior TC approach is used.
A thin flexible plastic catheter is carefully guided
through the cervix under ultrasound guidance to the
villi. A syringe attached to the catheter is used to
suction out a small amount of villi as the catheter is
withdrawn.
O The CVS procedure collects larger samples and
provides faster results than amniocentesis.
O Different from amniocentesis in that it does not allow
for testing for neural tube defects.

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O Associated risk/ Complications:
[Link]/ fetal loss (1% - 2%).
2. Oromandibular limb hypoplasia.
[Link] limb reduction defect-
• Increased risk is associated with decreased gestational
age at the time of CVS, highest susceptibility when CVS
if performed before 9 wks.
• Mechanism: thromboembolization or fetal hypoperfusion
through hypovolemia or vasoconstriction (based on
assumption that caused by some form of vascular
disruption). The limbs and mandible are susceptible to
such disruption before 10 weeks’ gestation.
• Overall risk for transverse limb deficiency from CVS is
0.03%–0.10%
[Link]- isoimmunization. 02/03/2016 23
 Amnicentesis
O USG guided percutaneous
withdrawal of amniotic
fluid for diagnostic purpose.
O Timing- between 14- 16wks.
O Indications:
• Karyotype (advanced maternal age)
• Fetal maturity
(L:S ratio, phosphatidylcholine or phosphatidylglycerol)
• Biochemical enzyme/amino acid/hormone analysis.
• Molecular genetic DNA diagnosis.
• α- fetoprotein(for NTDs) and
17-ketosteroid (for adrenogenital syndrome)02/03/2016 24
determination
O Method of amniocentesis:

Performed transabdominally (TA). During the

procedure, a needle is passed through the abdomen
and into the amniotic sac under continuous ultrasound
guidance. The needle stilette is removed once the
needle is in the correct position. A small sample of
amniotic fluid (10–20ml) is then removed using a
syringe attached to the needle.

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Complications of amniocentesis:
[Link] (risk about 1%).
Before 14 weeks of gestation (early amniocentesis)
has a higher fetal loss rate.
[Link] labor (stimulation of uterine contraction) or
PROM.
[Link] to fetus
[Link] puncture and bleeding with secondary
damage to fetus.
[Link]
6. Maternal sensitization to fetal blood (Rh-
isoimmunization) :- Anti D immunoglobulin to be
given to Rh –ve mother.
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 CVS Amniocentesis

What does it involve? Small sample of small sample of

placenta under amniotic fluid under
ultrasound guidance ultrasound guidance

When is the Between 10 and 14 After 15 weeks of

procedure usually weeks of pregnancy pregnancy
performed?
What is the risk of About 1 to 2 in 100 About 1 in a 100
miscarriage? women (1-2%) women (1%)

What technique is transabdominally (TA) transabdominally (TA)

used? and transcervically
(TC)

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 Cordocentesis
O Cordocentesis, or PUBS
(Percutaneous Umbilical Blood
Sampling), is the sampling of
blood from the umbilical cord.
O Objective: (a) prenatal diagnosis and (b) fetal
therapy.
O Timing: can be performed as early as 16 wks of
gestation but commonly performed between 18-22
wks of gestation for prenatal diagnosis.

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O Indication of cordocentesis:

(a) Prenatal diagnosis:

• Detection of anemia, hemoglobinopathies,

thrombocytopenia, acidosis, hypoxia, polycythemia

• Immunoglobuline M antibody response to infection

• Rapid karyotype and molecular DNA genetic

diagnosis.

(b) Fetal therapy:

• Transfusion or administration of drugs. 02/03/2016 29

O Method of cordocentesis:

Under ultrasound guidance needle is inserted in the

umbilical vein within the umbilical cord at its placental
end or fetal end. Upon entering the umbilical cord, the
stylet is removed and fetal blood is withdrawn into a
syringe attached to the hub of the needle.
The needle is withdrawn, then the puncture site is
monitored for bleeding, and the fetal heart rate is
assessed. After this procedure, the fetal heart rate and
uterine contraction are monitored for 1-2 hours.
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O Complications:

• Pregnancy loss, overall fetal loss risk of 1- 2%.

• Transient fetal bradycardia, manifestations of a

vasovagal response caused by local vasospasm, more
with umbilical artery puncture.
• Bleeding from the puncture site, cord hematoma.

• Fetomaternal hemorrhage

• Premature labor

• Infection

• Rh iso- immunization
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 Maternal serum test
(A) α- feto protein:
Incresed Decreased
• Twins Trisomies
• NTDs Aneuploidy
• Intestinal atresia
• Fetal demise
(B) Triple test: can detect 70% of Down syndrome
• Unconjugated estriol ↓ed
• α- feto protein ↓ed
• Β-HCG ↑ed
(C) Quad test: can detect 80% of Down syndrome.
• Unconjugated estriol ↓ed
• α- feto protein ↓ed
• β-HCG ↑ed
• Inhibin ↑ed
[Note: if only 1st trimester quad screen is used, α-feto protein is
recommended as a 2nd trimester follow up] 02/03/2016 32
 Down syndrome screening:
(A) 1st trimester:
• Fetal nuchal translucency (NT) thickness alone
≤70%
• NT with β-HCG & PAPP-A 87%
(PAPP-A = Pregnancy Associated Palsma Protein- A)

(B) 2nd trimester:

• Triple test 70%
• Quad test 80%

(C) Integrated screen:

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1st trimester screen + 2nd trimester screen detect 95%
 Maternal cervix
O Fetal fibronectin: indicates risk of preterm birth.

O Bacterial culture: identifies risk of fetal infection

(group B streptococcus, Neisseria gonorrhoeae).

O Fluid: determination of PROM.

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