9.genetic counselling

GENETIC COUNSELLING

CHAITANYA.PII MDSDept of Public Health Dentistry

Previous questions• Genetic counselling (Apr 2010, Oct 2012)

• Genetics and its applications in dentistry (Apr 2011)

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contents• Introduction• Genetic counselling• Genetic screening• Pedigree charting• Prenatal diagnosis• Conclusion• References

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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.

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Brief history Gregor Johann Mendel ( the father of genetics)

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Genetics • Genetics is defined as a branch of medical

science which concerned with the transmission

of characteristics from parents to offspring.

6Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn. Oxford: Oxford University Press, 1985.

General conceptGenetic: Branch of science which studies genes

and the pattern of inheritance of particular diseases

Inheritance: The passing of familial elements from

one generation to the next.

7Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn. Oxford: Oxford University Press, 1985.

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Gene – Basic unit of genetic information. Genes

determine the inherited characters. It is the

functional subunit of DNA and contain instruction for

making protein.

Chromosomes – storage units of genes. A structure

within the cell that deliver the genetic material as

DNA.

Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn. Oxford: Oxford University Press, 1985.

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DNA - is a nucleic acid that contains the genetic

instructions specifying the biological development of

all cellular forms of life Molecule encodes the

genetic information.

Genome – the collection of genetic information.

Carrier individual- individual who appear normal

but has one copy of mutant gene.

Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn. Oxford: Oxford University Press, 1985.

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Phenotype: an appearance or characteristic of an

individual, which results from the interaction of the

person’s genetic makeup and his/her environment.

Genotype: the genetic constitution (genome) of a

cell, an individual or an organism.

Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn. Oxford: Oxford University Press, 1985.

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Autosomal Dominant: it is one of several ways that

a trait or disorder can be passed down through

families.

(Or)

A gene on one of the non-sex chromosomes that is

always expressed, even if only one copy is present.

Autosomal recessive: A pattern of inheritance in

which both copies of an autosomal gene must be

abnormal for a genetic condition or disease to occur

Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn. Oxford: Oxford University Press, 1985.

They are of 3 types:

1.Chromosomal abnormalities

2.Mendelian diseases

3.Multifactorial disorders

CLASSIFICATION OF GENETIC DISORDERS

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1.CHROMOSOMAL ABNORMALITIESA. Klinefilter syndromeB. Turners syndrome.

2.MENDELIAN DISEASESA. DominantB. RecessiveC. Sex linked diseases

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3.MULTIFACTORIAL DISORDERS

A. HypertensionB. DiabetesC. Congenital heart disease

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Genetic counselling

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Genetic counsellingGenetic 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.

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• 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” (NSGC, 2005).National Society of

Genetic Counselors

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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

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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.

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• 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 

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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.

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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.

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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.

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The counselor tends to give advice, make decision,

be coercive, persuasive, influencing, directing and

controlling.

The counselor communicates, enables, explores,

encourages, informs, offers choices, discusses,

promote autonomy, is empathic, non-judgmental,

and respectful of the client.

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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.

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Function of genetic counselling session

Provide information

Available solution

Help person to understand and cope with his

condition

Testing the risk of recurrence

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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

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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

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STEPS OF GENETIC COUNSELLING:

• Diagnosis • Prognosis • Treatment

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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

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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.

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They are of 2 types:

1.Prospective2.Retrospective

GENETIC COUNSELLING

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1. Prospective genetic counselling

This allows for the true prevention of disease.

This approach requires

Identifying 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.

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If heterozygous marriage can be prevented or reduced,

the prospects of giving birth to affected children will

diminish.

EX: Sickle cell anemia

Thalassemia

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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.

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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

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Ref: Genomics and world health: Report of the advisory committee on health research, Geneva, WHO (2002).

• 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.

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Ref: Genomics and world health: Report of the advisory committee on health research, Geneva, WHO (2002).

Genetic screeningDefinition:

A search in apparently normal population for

individual with abnormal genes which increase their

risk or their offspring of being affected by a disease.

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Types of genetic screening1. Carrier identification

2. Prenatal diagnosis

3. Newborn screening

4. Forensic screening ( paternity test)

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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.

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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.

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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.

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

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Prenatal diagnosis

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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.

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Let us now consider the 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 preg nancy.

•Lastly the termination of pregnancy should be

acceptable to the concerned couple.

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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

Approaches to prenatal diag nosis

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1. Amniocentesis

2. Chorion villous biopsy

3. Ultrasonography

4. Foetoscopy

5. Foetal blood sampling Prenatal Diagnosis

6. Maternal blood screening

7. Preimplantation diagnosis

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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.

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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.

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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

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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.

.

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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 defects like anencephaly, spina-

bifida, micro cephaly, hydrocephalous, etc.

5. Limb defects are also evident on ultrasound

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FOETOSCOPY

The procedure involves visualisation of foetus using a

fibre optic self-illumi nated 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.

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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:

3. Sickle cell disease

4. Thalassaemias

5. Haemophilia A

6. Duchenne muscular dystrophy

7. Immune deficiency disorders

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.

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PREIMPLANTATION DIAGNOSIS

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

fertilisa tion (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).

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Demerits and Limitations

1. Despite PCR even in the best hands, procedure

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

2. 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.

1.HEALTH PROMOTIONAL MEASURES:

A.EUGENICS:

a. Negative eugenics:

AIM: To reduce the frequency of hereditary disease

and disability in the community to as low as possible

PREVENTIVE AND SOCIAL MEASURES

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B.POSITIVE EUGENICS:

AIM: To improve the genetic composition of the

population by encouraging carriers of desirable

genotypes.

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B.EUTHENICS :

Studies with mentally retarded children indicated that

exposure to environmental stimulation improved their

IQ.

This environmental manipulation is called euthenics.

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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

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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.

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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.

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SPECIFIC PROTECTION:

Patients undergoing x-ray examination should be

protected against unnecessary exposure of the

gonads to radiation.

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Rh haemolytic disease of the newborn which is a

genetically determined immunological disorder is

now preventable by immunization by anti D globulin.

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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.

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Reference 1. Jorde Lynn B. Medical Genetics. Mosby,

2005.

2. King RC, Stansfield WD. Dictionary of

Genetics. 3rd edn. Oxford: Oxford University Press, 1985.

3. Harper P. Practical Genetic Counselling.

Oxford: Butterworth Heinemann,1993.

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4. Brock DJH, Rodeck CH, Ferguson Smith MA. Prenatal Diagnosis and

Screening. Edinburgh: Churchill Livingstone, 1992.

5. Lilford RJ. Prenatal Diagnosis and

Prognosis. London: Butterworth,1990.

6. K.park’s textbook of preventive and social medicine. 2015, 23rd edition, bhanot publishers.

7. Genomics and world health: Report of the advisory committee on health research, Geneva, WHO (2002).

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