GENETIC

COUNSELLING

Dr Sanjeev Gupta
Professor, LNMC, Bhopal
 Previous questions
• Genetic counselling

• Genetics and its applications.

2
Contents
• Introduction

• Genetic counselling

• Genetic screening

• Pedigree charting

• Prenatal diagnosis

• Conclusion

• References
3
 Genetics

• The term genetics was introduced by

Bateson in 1906. It has been derived from
Greek word ‘gene’ which means ‘to
become’ or ‘to grow into.

4
Brief history
Gregor Johann Mendel
( the father of genetics)

5
Genetic counselling

6
 Genetic counselling

Genetic counseling is a process by which patients or

relatives,
• At risk of an inherited disorder, are advised of the
consequences and nature of the disorder.
• The probability of developing or transmitting it and
the options open to them in management and family
planning in order to prevent or avoid it.
7
• Genetic counselling
• Is the process of helping people understand and adapt to the
medical, psychological and familial implications of genetic
contributions to disease.

• This process integrates the interpretation of family and

medical histories to assess the chance of disease occurrence
or recurrence, education about inheritance, testing,
management, prevention, resources and research, and
counseling to promote informed choices and adaptation to the
risk or condition.
8
 Aims of genetic counselling
• The genetic counseling aims to provide the family with
complete and accurate information about genetic disorders.
1. Promoting informed decisions by involved family members
2. Clarifying the family’s options available treatment and
prognosis
3. Explaining alternatives to reduce the risk of genetic
disorders
4. Decreasing the incidence of genetic disorders
5. Reducing the impact of the disorders

9
 WHO ARE GENETIC COUNSELLERS ?

• Postgraduates health professionals with a graduate diploma

or Master's in genetic counseling.

• Experience in the areas of medical genetics and counseling.

• Identify family at risk, investigates the problems present in

the family, interpret information about the disorder, analyze

inheritance patterns and, risk of re-occurrence & review

available option with the family.

10
• Serves as educators and resource people for other health

care professionals and for general public.

• work in administration capacities.

• A team of physician, nurse and social worker who

undergone special training in genetic counseling

• Many engage themselves in research activities related to

the field of medical genetics & genetic counseling

11
 WHAT IS THE ROLE OF GENETIC COUNSELLING ?

Genetic Counselors provide genetic information. It is their

counselling skills, including their ability to empathically
connect with their patients that leads to demands for their
skills.

Good Genetic Counselor have many strengths. They make

their clients’ best interest their foremost priority and are
keenly attuned to complex professional and ethical
challenges.
12
 Genetic Counselor use non-directive counseling
method to provide the best service to those who need
them

To develop a mutual relationship with the client, to

understand her or him, to relieve any psychological
distress, promote a sense of control, and help find
solution to specific problems.

13
Assess the client’s strengths, values and needs;

provide an individualization and flexible counseling

style to suite each client’s need and agenda;

develop an awareness of self; and attend to their

own inner life.

14
The counselor tends to give advice, make decision, be
coercive, persuasive, influencing, directing and controlling.

The counselor communicates, encourages, informs, offers

enables, explores, discusses, choices, promote autonomy, is

empathic, non-judgmental, and respectful of the client.

15
 PRE-REQUISITES OF GENETIC COUNSELLING IS
• Detailed family history.

• Accurate diagnosis.

• Understanding the medical aspect of the disorder (etiology,

natural history, treatment, prognosis, burden ).

• Understanding the inheritance pattern ( recurrence risk )

• Understanding the psycho-social impact of the information.

• Training / experience in counselling techniques.

• Understanding the concepts of health / disease / healthcare in

the appropriate cultures.
16
 Function of genetic counselling session

 Provide information
 Available solution
 Help person to understand an cope with his condition
 Testing the risk of recurrence

17
 INDICATIONS FOR GENETIC COUNSELLING

1. Hereditary disease in a patient or family

2. Birth defects

3. Mental retardation

4. Advanced maternal age

5. Early onset of cancer in family

6. Miscarriages

7. Malformations

8. Tendency to develop a neurologic

conditions

18
 INFORMATION CONVEYED IN GENETIC COUNSELLING

1.Magnitude of risk of occurrence or recurrence

2.Impact of disease on patient and family

3.Modification of disease impact or risk

4.Anticipated future development

19
 STEPS OF GENETIC COUNSELLING:

• Diagnosis

• Prognosis

• Treatmen
t

20
 Genetic counselling ethics

• Respect the right of individual

• Non- directive approach

• Keep privacy of individual and family

• Maintain the communication between counsellor and his client

21
 IN SHORT GENETIC COUNSELLING IS
Determine the facts :

•Diagnosis, etiology, and inheritance patterns, prognosis, natural history,

treatment and re-occurrence of risk.

Transmitting the information :

•To those requesting it in a sensitive, culturally appropriate, understandable

way.

Supporting the decision :

•Supporting the decision making process of the couple.

Genetic counselling :

•It is non-directive.
22
 GENETIC COUNSELLING
They are of 2 types:

1.Prospective
2.Retrospective

23
 1. Prospective genetic
counselling

This allows for the true prevention of disease.

This approach requires identifying individuals for any heterozygous defect by

screening

Explaining to them the risk of their having affected children if they marry
another heterozygote for the same gene.

24
If heterozygous marriage can be prevented or reduced, the prospects
of giving birth to affected children will diminish.

EX: Sickle cell

anemia

Thalassemia

25
2. Retrospective genetic counselling:

Most genetic counselling at present is retrospective, i.e, the hereditary

disorder has already occurred within the family .

The methods which could be suggested under retrospective

genetic counselling are:

1.Contraception

2.Pregnancy termination.

26
 A survey carried out by the WHO showed that genetic advice was
chiefly sought in connection with congenital abnormalities

• Mental retardation

• Psychiatric illness

• Inborn errors of metabolism

• Premarital advice

Ref: Genomics and world health: Report of the advisory committee on

health research, Geneva, WHO (2002). 27
• The WHO recommends the establishment of genetic
counselling centers in sufficient numbers in regions
where infectious disease and nutritional disorders
have been brought under control

• And in areas where genetic disorders have always

constituted a serious public health problem.

Ref: Genomics and world health: Report of the advisory committee on

health research, Geneva, WHO (2002). 28
 Genetic screening

Definition:

A search in apparently normal population for

individual with abnormal genes which increase their
risk or their offspring of being affected by a
disease.

29
 Types of genetic screening

1. Carrier identification

2. Prenatal diagnosis

3. Newborn screening

4. Forensic screening ( paternity

test)

30
 EARLY DIAGNOSIS AND TREATMENT:

1.DETECTION OF GENETIC CARRIERS :

It is possible to identify the healthy carriers of a number of

genetic disorders, especially the inborn errors of
metabolism.

31
2.PRENATAL DIAGNOSIS:

INDICATIONS:

-Advanced maternal age

-Previous child with chromosome aberration

-Intrauterine growth delay

-Biochemical disorders

-Congenital anomaly

-Screening for neural tube defects and trisomy.

32
 Pattern of inheritance
• Human cell contain 23 pairs of
chromosomes. 22 pairs autosomal and one
pair sex chromosomes.

• 23chromosomes inherited from mother

and 23 chromosomes from father.

• Sex chromosomes: XX for female and XY

for male.

33
Genetic pedigree: a diagrammatic representation of
diseases history in a family up to 3rd degree relative.

43
35
 Prenatal diagnosis

Prenatal diagnosis forms an integral step in genetic

counselling. In fact, for couples at risk of a disorder, it is
desirable to consider, plan and discuss prenatal diagnosis
even before pregnancy. Discussion and planning beforehand
will eliminate hurried procedures and emotional trauma as
well.

36
Let us now considerthe following situations that warrant
prenatal diagnosis:
It is essential for a genetic disorder in which treatment is
either absent or unsatisfactory.
Disorder in which an accurate prenatal diagnostic test is
possible.
Risk to the pregnancy is sufficiently high.
The genetic disorder itself is severe enough to warrant
termination of pregnancy.
Lastly the termination of pregnancy should be acceptable to
the concerned couple.

37
In the following cases, prenatal diagnosis is a must:
•Maternal age above 35-40 years.
•If one of the parents is a balanced translocation
carrier.
•In case of an autosomal or X-linked recessive
metabolic disorder that is severe but detectable
prenatally.
•Couple already has one child with a neural tube
defect

38
 Approaches to prenatal diagnosis

1. Amniocentesis

2. Chorion villous biopsy

3. Ultrasonography

4. Foetoscopy

5. Foetal blood sampling Prenatal Diagnosis

6. Maternal blood screening

7. Preimplantation diagnosis 39
 Amniocentesis

• The ideal time to undertake this investigation is between

14 and 16 weeks when a sufficient amount of amniotic
fluid is available for tapping, without harming the
conceptus.
Procedure:
• Under ultrasound control, placental localisation is done.
• Then under local anaesthesia, the fluid is tapped per
abdomen avoiding injury to the placenta.
• A clear tap, not a blood-stained one, must be ensured.
About 10-20 cc of fluid is taken out and is subjected to
analysis in the laboratory. The cells and fluid are
separated by centrifugation. The cells can be studied
directly or subjected to culture studies for obtaining
foetal karyotype. 49
CHORION VILLOUS BIOPSY

In this procedure, chorionic villi are aspirated with the help of canula, which
is introduced through the cervix uteri. The procedure is done under
ultrasound control. The ideal time to perform chorion villous sampling
(CVS) is 8-10 weeks period. However, it may be undertaken till almost 12
weeks.

41
 Merits

1. As compared to amniocentesis, CVS claims an advantageous

position because it is possible at a much earlier stage of
gestation and is easily accepted by patients.
2. Faster result is possible because chorion villi contain
enough cells under mitosis so as to permit chromosome
analysis without culture.
If the results indicate abnormality in CVS, then termination of
pregnancy is safer and simpler in first trimester than after
amniocentesis (around 18 weeks), which amounts to second
trimester abortion
42
ULTRASONOGRAPHY

The underlying principle in this procedure is that the echoes generated by the
reflection of ultrasound waves are displayed in one of the two ways:

1. B (brightness) Mode: In this, a cross-section of the anatomy

is created as transducer is moved across an area.
2. Real Time Imaging: In this, repetitive B-mode images are generated in rapid
sequence, allowing appreciation of motion.
.

43
 Basically, ultrasound serves as an ancillary to amniocentesis.
It is helpful in the following ways:

1. Localisation of placenta in amniocentesis or CVS

2. To ascertain gestational age
3. Exclude multiple pregnancy

4. To recognise spina- , bifida,

defects like anencephaly
microcephaly, hydrocephalous, etc.
5. Limb defects are also evident on ultrasound

44
FOETOSCOPY

The procedure involves visualisation of foetus using

a fibre optic self-illuminated instrument called
foetoscope. It is inserted in the amniotic cavity under
local anaesthesia. It is usually done around 18-22
weeks of gestation. With this, one can detect limb
malformations, facial defects (cleft lip, cleft palate,
ear defects) or defects involving the genitals.

The procedure carries a risk of abortion to the tune

of 3%-5%. Foetoscopy is useful in obtaining
foetoscopic skin biopsy and foetal blood sampling.

45
FOETAL BLOOD SAMPLING (FBS)

It can be done in two ways:

1.Placental aspiration (indirect tap)

2.Sampling under direct vision
In the former technique, both maternal and foetal blood cells are mixed
need to be separated before sample processing. In the second case, sample
is obtained under direct vision using a foetoscope. Both techniques carry
about 10% risk of abortion. There are number of conditions in which FBS is
needed to make prenatal diagnosis. They are as follows:

1.Sickle cell disease

2.Thalassaemias

3.Haemophilia A
4.Duchenne muscular dystrophy
5.Immune deficiency disorders 46
MATERNAL SERUM SAMPLE

•Estimation of AFP(alpha-fetoprotein) in maternal serum is used

as a screening test for the detection of neural tube defect. This
test is advocated for all pregnant women, realising the fact that
about 90% babies with a neural tube defect are born to couples
having no family history of such disorder.

•Maternal serum shows AFP increment during 16-18 weeks of

gestation. Elevated AFP in maternal serum is encountered in
other conditions, e.g. twin pregnancy and missed or threatened
abortion. Having noted elevated AFP, the patient is referred for
ultrasonography and subsequently amniocentesis.
47
PREIMPLANTATION DIAGNOSIS

•It involves egg retrieval from the female followed by in vitro

fertilisation (IVF). The fertilised oocyte is allowed to develop in
vitro up to 8 cell stage. A single cell (blastomere) from this
group is removed, its DNA extracted and amplified by PCR
and then analysed to see if there is genetic disorder.
• If the analysis does not reveal any defect, the conceptus is
implanted into the mother's womb. In X-linked recessive traits
such as Duchenne muscular dystrophy, the preimplantation
diagnosis is used to determine sex of conceptus (since only
males are affected). 48
Demerits and Limitations

•Despite PCR even in the best hands, procedure using

single cell meets a failure rate of 10%-20%.

•There is a significant risk of false results because of

contamination.
•Hence, it is safe that an adverse result of preimplantation
diagnosis should be followed by invasive prenatal diagnosis
using CVS for confirmation.

49
 PREVENTIVE AND SOCIAL MEASURES

1.HEALTH PROMOTIONAL
MEASURES:

EUGENICS:

a. Negative eugenics:

AIM: To reducethe frequency of hereditary disease and disability in the

community to as low as possible

50
B.POSITIVE EUGENICS:

AIM: To improve the genetic composition of the population by

encouraging carriers of desirable genotypes.

51
B.EUTHENICS :

Studies with mentally retarded children indicated that

exposure to environmental stimulation improved their IQ.

This environmental manipulation is called euthenics.

52
 OTHER GENETIC PREVENTIVE MEASURES

1.CONSANGUINEOUS MARRIAGES:

When blood relatives marry each other there is an increased risk

in the offspring of traits controlled by recessive genes and those
determined by polygenes.

EX: Albinism, Alkaptonuria, Phenylketonuria

53
An increased risk of premature death is also noted in such offspring.

Therefore, a lowering of consanguineous marriages would be

advantageous to the health of the community.

54
2.LATE MARRIAGES:

Trisomy or mongolism is more frequent in children born of elderly

mothers.

Hence early marriage of females is better than late marriage from the
point of view of preventing mongolism.

55
SPECIFIC PROTECTION:

Patients undergoing x-ray should be

examination
exposure of the
protected against unnecessary
gonads to radiation.

Rh haemolytic disease of the newborn which is a

genetically determined immunological disorder is now
preventable by immunization by anti D globulin.

56
 Conclusion
• Many diseases have genetic root

• The genetic screening is an essential issue in most

stages of the life.

• Genetic counselling aim is to bridge the gap for

people between genetic field complexity and their
life.

57