Genetic counselling - a review

GENETICGENETIC
COUNSELINGCOUNSELING
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CONTENTSCONTENTS
Introduction
Trends in genetic diseases
Genetic Counseling
◦ Definition
◦ Indications for genetic counseling
◦ Genetic counseling team
◦ Genetic counseling facilities
◦ Goals of genetic counseling
◦ Counseling process
◦ Problems in counseling
◦ Organization of Genetic counseling
Public health importance
Conclusions
References
Genetic counseling 2

Gregory Johann Mendel (July 20, 1822-
January 6 1884) was an Augustinian priest and
scientist
Father of genetics for his study of the
inheritance of traits in pea plants.
He conducted his study in the monastery's garden.
Between 1856 and 1863 Mendel cultivated and
tested some 29,000 pea plants.
This study showed that one in four pea plants had
purebred recessive alleles, two out of four were
hybrid and one out of four were purebred
dominant.

INTRODUCTIONINTRODUCTION
Genes are the units of hereditary.
They contain the hereditary information
encoded in their chemical structure for
transmission from generation to generation.
It is said that we inherit about 50000 genes from
mother and 50000 genes from father.
These genes occupy a specific position on the
chromosomes.

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Gene is a sequence (a string) of bases.
It is made up of combinations of A, T, C, and G.
These unique combinations determine the gene's
function, much as letters join together to form
words.
Each person has thousands of genes -- billions of
base pairs of DNA or bits of information repeated in
the nuclei of human cells --which determine
individual characteristics

If the genes comprising a pair are alike (AA), the
individual is described as 'homozygous' for that
gene.
If the genes comprising a pair is different then the
individual is described as 'heterozygous' .
A gene is said to be dominant when it manifests
its effect both in the heterozygous and the
homozygous state.
A gene is said to be recessive when it manifests
its effect only in the homozygous state.

Many instances are known in which the same
character controlled by several genes like colour
of one skin, height & weight, life span, degree of
resistance to disease, rate of heart beat, blood
pressure and many other inherited traits.
These genes may occupy separate positions in
the chromosomes.
The extent to which a genetically determined
condition is expressed in an individual is called
'penetrance'.
Lack of penetrance is one reason for skipped
generation and unexpected pedigree patterns.

Mutation:
Conversion of normal genes into abnormal ones.
It is a regular phenomenon in nature. The natural
mutation is increased by exposure to mutagens such
as ultraviolet rays, radiation, chemical carcinogens,
virus and genetically determined host factors.
Maternal age is an important predisposing factor.
Genotype refers to the total genetic constitution of
an individual.
Phenotype refers to the outward expression of the
genetic constitution.

Genetic DiseasesGenetic Diseases
Genetic disorders are broadly classified as
◦ Chromosomal abnormalities
◦ Unifactorial (single gene or Mendelian
disease)
◦ Multifactorial disorders

Chromosomal abnormalities' Numerical
or structural alterations occur from time to
time in human beings.
They arise in various ways:
◦ Non Disjunction
◦ Translocation
◦ Deletion
◦ Duplication
◦ Inversion

Chromosomal disorders involve the lack,
excess or abnormal arrangement of
chromosomes.
Relating to sex chromosomes
◦ Klinefelters syndrome
◦ XYY syndrome
◦ Turners syndrome
◦ Super Females
Relating to Autosomes
◦ Mongolism or Down’s Syndrome

Mendelian diseases:
Inherited according to the mendelian
laws.
These are the
◦ Dominant
◦ Recessive and
◦ Sex linked diseases.

Mutation: origin of genetic disorders is mutation
It refers to any stable changes in the genetic
material
Many mutations are virtually neutral in their
selective effects.
The probability that a random mutation will have
a beneficial effect is very small, consequently
most mutations with any detectable selective
effect are in fact deleterious.
In this way mutations give rise to aggregate to the
burden of abnormal genotypes.

During recent decades, human genetics has
seen enormous progress.
Family studies indicated a genetic component
for more complex diseases, so called “empiric
risk”
This empiric risk figures were to predict
recurrence risk, were used for genetic
counseling.

Multifactorial diseases:
The frequency is high compared with that of
chromosomal disorders.
There are indications that most of the
common disorders of adult life such as
◦ Essential hypertension
◦ Schizophrenia
◦ Mental retardation
◦ Congenital heart disease
◦ Duodenal ulcer etc are condition with
multifactorial etiology

The mode of inheritance of multifactorial
disorders is complex because
environmental factors are also involved.
The relative contributors of genetic
predisposition and environmental factors
to the etiology will vary greatly from
patient to patient.

In the last decade several aspects
of human genetic that are relevant
to medicine and public health have
been considered by WHO expert
committees and scientific groups.

Interest in disease of genetic origin results from
several considerations:
◦ Absolute and relative decline in morbidity and
mortality attributable to infection, parasitic
infection and malnutrition.
◦ Relative increase in morbidity and mortality
attributable to genetic factors resulting from the
slow changes in gene frequencies.
◦ Over 2,300 hereditary diseases have been
identified and more are added to the list every year.
◦ Genetically conditioned diseases with a clear
genetic component account for 25-40% of all cases
treated by the health services.
◦ Development of promising approaches to the diagnosis,
treatment and prevention of genetic diseases.
Genetic counseling
21

Empiric Risk of Recurrence ofEmpiric Risk of Recurrence of
Isolated Malformation.Isolated Malformation.
(S.R. Phadke 2004)(S.R. Phadke 2004)
Malformation Frequency per 1000
births
Recurrence (%) for
normal
parents of one affected
child
Anencephaly/spina bifida 4-5 5
Cardiac malformation 6-8 3-4
Cleft lip and cleft palate 2 4-5
Cleft palate alone 0.5 2-6
Pyloric stenosis 2-3 3
Talipes equinovarus 3-4 2-8
Dislocation of hip 3-4 3-4
Hirchsprung disease 0.1 6

In a world that views population
growth as an important problem and
is increasingly concerned with the
quality of human life, it will be
taken for granted that children
should be free of genetic disease.Genetic counseling 23

Accurate knowledge about the
epidemiology of genetic disease is an
important prerequisite of action by a
particular community concerning
prevention, treatment and rehabilitation.
Human genetics is much more than than
the study of mere hereditary disease. It
has emerged as a basic biological since for
understanding the endogenous factors in
health and disease and the complex
interaction between nature and nurture.

The strategy of the human geneticist must
be to attempt to lessen the harmful effects
of mutation, while at the same time
preserving the genetic variation in the
population that is essential for adaptation
and evolutionary process.

'Population genetics’:
It has been defined as the study
of the precise genetic composition
of population and various factors
determining the incidence of
inherited traits in them.

Genetic diseases have lately emerged as a
significant cause of morbidity and
mortality.
As most of the genetic diseases present
early in life, it is of utmost importance for
pediatricians to realize the importance of
genetic counseling in the management of
children with genetic disorders and to
develop the necessary expertise.

DefinitionDefinition
The process by which patients or relatives at
risk of a disorder that may be hereditary are
advised of the consequences of the disorder,
the probability of developing or transmitting
it, and of the ways in which this may be
prevented, avoided or ameliorated
Peter Harper
 This complex process can be seen from diagnostic
(the actual estimation of risk) and supportive
aspects. Genetic Counseling 28

The American Society of Human Genetics (1975) defines
Genetic Counselling as a communicative
process which deals with the human problems
associated with the occurrence or risk of
recurrence of a genetic disorder in a family.

 The person who seeks genetic counseling is called the
consultand or counsellee and the one who gives it is the
counsellor.
 Obective of genetic counseling
 To make the individual or the family to understand the
scientific information about the disease, thus helping them
to cope with the problem of genetic disorder and to reach a
reproductive decision.

Genetic CounselorsGenetic Counselors
A genetic counselor is a medical genetics
expert with a master of science degree.
Most enter the field from a variety of
disciplines, including biology, genetics,
nursing, psychology, public health and
social work.

The counselor’s job is simply to estimate the risk
& try to ensure that it is understood.
The demand for advice continues to grow as the
public becomes better informed from many sources
and referrals to genetic clinics certainly increase as
the availability of specialist advise become known.
The pre-requisites for adequate estimations of risks
are as accurate a diagnosis as possible and a
knowledge either of the mechanisms of inheritance
of the trait or availability of data, on which to base
empirical estimates

Often the condition & clinical terms have to
be specified in genetics before advice can be
given.
A good family history is necessary for
investigation. This when adequately confirmed
can either serve definitely to identify the genetic
makeup of the parents or a parent or in the case of
traits.
Where there is predisposition not determined
by single genes it may be important in
determining the level of risk for a particular
patient. Genetic counseling 33

 Family history should be recorded in diagrammatic
pedigree form and should include live births still, births
and miscarriages in the according & succeeding generations.
 Each individual in the pedigree should be identified
by name, dates and place of death. This will enable
hospital records and death certificate to be traced.
 Pedigree
 Pedigree (at least 3 generations) is constructed using
standardized set of symbols. Direct questions need to be
asked for similarly affected individuals, miscarriages, early
deaths, consanguinity, major and minor malformations
34

Risks are given in simple factors (in preference to
% or decimal).
It is clear in all these situations particularly where
risks are derived empirically, the fraction given is
a mean or average value for, although it is fully
recognized that in differing circumstances the range
may be wise.
The best estimate is the one derived as the
average of many families.
The distinction between the common traits, which
are usually harmless and the rarer disease states
needs to be particularly emphasized in
educational campaigns.

EXAMINATIONEXAMINATION
 A complete physical examination and relevant anthropometric
measurements are necessary.
 In a case with dysmorphology correct description of facial
features, minor malformations, normal variants need to be
noted down.
 A photographic record of dysmorphic child is essential as it is
much better than a lengthy description.
 Examination of parents may be needed to verify whether a
dysmorphic feature (e.g., shape of ears) is of diagnostic
significance or a normal familial feature in that family.

 Investigations of Family Members
 A careful clinical examination and investigation of
parents and family members for mild manifestations can
be of great use in genetic counseling as variable
expression is characteristic of many autosomal dominant
conditions
 Ex: Parents of a child with tuberous sclerosis or
neurofibromatosis. If one of the parents is having any
feature of tuberous sclerosis, then the risk of recurrence
is 50% while in case both the parents are normal, there
is no significantly increased risk of recurrence.
 Similarly, a single central incisor in a parent of a child
with holoprosencephaly will suggest autosomal
dominant inheritance.

APPROACH TO GENETICAPPROACH TO GENETIC
COUNSELINGCOUNSELING
The counselor in medical genetic generally uses
non-directive counseling, with the responsibility
being education of the family.
However, the counseling session is not merely a
litany of facts (e.g., recurrence risks) but is colored
with the counselor's own experiences and
opinions.
For the couple or the family seeking counseling, the
information received may have long-term
consequences and will often be used as part of the
information necessary for decision-making.

INDICATIONS FOR GENETIC COUNSELINGINDICATIONS FOR GENETIC COUNSELING
◦ Change with time as new methods of diagnosis become
available or as specific therapies are developed.
1. Advanced maternal age ( prenatal diagnosis is offered
to pregnant women at 35 years of age or older ).
2. Known or suspected hereditary condition in family
( e.g. a malformation, mental retardation, or several
relatives with a specific type of malignancy)
3. A fetus or child with birth defects, including either
single or multiple malformations
4. A child with mental retardation
5. Recurrent spontaneous abortions
6. Exposure to know or suspected teratogens
7. Consanguinity

 Skeletal dysplasia-Disporportionate short stature.
 Neurodegenerative diseases, e.g., ataxias,
leukodystrophy.
 Myopathy.
 Known genetic diseases, e.g., thalas-semias, Wilson
disease, hemophilia, mucopolysaccharidosis, Down
syndrome and other chromosomal disorders.
 Any unusual disease of skin, eyes, bones, or unusual
facial features.
 Deafness.
 Familial cancers or cancer prone disease.
 Ambiguous genitalia or abnormalities of sexual
development.

 1: Pediatr Endocrinol Rev. 2006 Aug;3 Suppl 3:437-46.
Links
 Erratum in: Pediatr Endocrinol Rev. 2007 Sep;5(1):470.
Consanguinity among the Arab and Jewish
populations in Israel.
 Jaber L, Halpern GJ.
 Bridge to Peace Community Pediatric Center, Taibe,
Israel. jabe@bezeqint.net

 Consanguineous marriages are associated with many
problems, although the prevailing opinion is that the
advantages outweigh the disadvantages.
 This explains why the custom is still extremely prevalent,
particularly in Arab countries, India and small isolated
communities.
 Among Israeli Arabs there has been a reduction in the rate
of such marriages, although it is still sufficiently high to
cause medical problems.
 Among Israeli Jews, the rate has always been much lower.
genetic counseling and prenatal testing where available in
order to reduce the health problems even further.
 Ongoing research in order to identify specific genes will
enable more conditions to be detectable early in
pregnancy. We expect that the willingness of families to
agree to termination of affected pregnancies will reduce
the number of babies born with these conditions.

GENETIC COUNSELING TEAMGENETIC COUNSELING TEAM
Genetic counseling is most effectively done
using a team approach to convey
information to a family.
◦ Medical specialist
◦ Genetic Counselor
◦ Additional members

Medical Specialist
Often trained in a primary medical specialty(e.g.
pediatrics), with additional training as a clinical
geneticist.
Specific medical genetics residency programs are
available.
The role of the medical or clinical geneticist is to
establish the diagnosis and to counsel patients
regarding the medical implications of the conditions.
In many counseling situations, the clinical geneticist
plays a consultant role.

Genetic counselor
May be either formally trained or experienced in the
area of genetic counseling.
Counselors come from a variety of backgrounds,
including nursing, social work, and education
Formal training programs involve a master's degree
after an undergraduate education with an emphasis
on science and psychology.
The role of the counselor is to be involved in the
counseling process, support, and follow-up of the family.

Additional members
Medical specialists consulted for specific
investigation and opinions.
Ongoing family support may also be given by
social workers, religious support persons, and parent
and lay groups.
For some genetic disorders (e.g., Hemophilia),
counseling may be provided within disease-
specific clinics by a physician or other health
professional.
Family physicians and primary medical
specialists provide genetic counseling to patients
in a number of situations.

GENETIC COUNSELING FACILITIESGENETIC COUNSELING FACILITIES
Teaching or university based tertiary
care hospitals
Component of a specialized
multidisciplinary clinic
Screening programs

Teaching or university-based tertiary
care hospitals.
These centers are involved in counseling
services
The education of other professionals,
fellows, and the lay public
Research into genetic conditions (clinical
and basic research).

Component of a specialized
multidisciplinary clinic
In such a Clinic ( e.g. for spina bifida),
the provision of genetic counseling
is part of the overall service to the
family.

Screening programs
e.g, for maternal serum screening in pregnancy
 Provide a specific service to a large number of
families.
Only patients with abnormal results may be
formally counseled.
Outreach programs
Generally run from a tertiary care center and
provide local service on an intermittent basis

GGoals of Genetic Counselingoals of Genetic Counseling
American society of Human genetics
(1975)
To help patient or family
◦ Comprehending medical facts
◦ Understanding the mode of inheritance and
recurrence risks
 Origin of risk
 Couples may appreciate risk in different ways
Binary
Comparison of losses and gains
Numerical Risk
◦ Understanding the options
◦ Choosing the course of action
◦ Adjusting the condition

Comprehending the medical facts
After the most precise diagnosis is made,
the diagnosis, prognosis, appropriate investigations
needed, and ongoing management of the condition
are discussed with the family.
If a diagnosis is not possible, the counseling
should present what is understood as well as
uncertainties regarding prognosis or inheritance.

Understanding the mode of inheritance
and the recurrence risks.
The inheritance should be clearly explained (the
use of diagrams and examples may be helpful) to
the parents or to other family members.
Recurrence risks may involve standard
Mendelian genetics, calculated risks, or risks
observed in the population (empiric)

◦ The origin of the risk and whether it pertains to a
specific diagnosis (e.g. cystic fibrosis) or to a
non-specific diagnosis (e.g.mental retardation)
◦ Couples may appreciate risk in different ways.
 1) Binary. Two states are seen: The condition will or will
not happen again
 2) Comparison of losses and gains. The condition is
analyzed according to may determine the decision to
have another pregnancy.
 3) Numerical risk is expressed either as percentage (e.g.
50%) or as a fraction (e.g. 1/2).

Understanding the options.
When faced with a distinct recurrence
risk, the reproductive options for the
couple may include methods of
contraception, adoption, insemination by
donor sperm, use of donated ova, prenatal
diagnosis with or without termination of
the affected fetus.

Choosing a course of action.
The coupled is encouraged to choose the
best course for themselves in light of the
recurrence risk, the perceived burden (e.g.
psychological, social, economic), the
goals of the family, and their religious and
ethical standards.

Adjusting to the condition:
The role of the counselor is to assess the
family's reaction to the diagnosis and recurrence
risk, Follow-up counseling, by either the
medical genetics team or a psychologist, may be
indicated to help the family deal with the
condition effectively.

COUNSELLING PROCESSCOUNSELLING PROCESS
To achieve the goals of genetic counseling,
the family must be able to receive the
information presented and convert the
facts into a part of their decision making.

The counseling team (i.e. the medical
geneticist and the genetic counselor)
interacts with the family most effectively
by:
◦ Having information required for counseling at
hand
◦ Recognizing the psychological and emotional
burdens
◦ Recognizing factors that affect counseling
◦ Provide non directive counseling
◦ Helping family relieve feelings of shame and
guilt
◦ Helping family identify its personal goals
◦ Recognizing counselor biases.
◦ Follow-up genetic counseling

Having information required for
counseling at hand.
This may require documenting the
family history, collecting records,
and examining individuals.

Recognizing the psychological and
emotional burdens associated with the
diagnosis, families may experience guilt and
shame after the diagnosis of a genetic
condition in a family member,
Realistic guilt feelings may exist
Ex: When a women chosen not to have prenatal diagnosis and
delivers an infant with Down syndrome.
Unrealistic guilt feelings are seen when the
individual feels response to a failure to reach certain goals and
standards.
Shame may be masked by denial, re-labeling the losses as gains (e.g.,
We were chosen to have this child because of our strength"), or by
finding fault with others. Genetic counseling 62

Recognizing factors that affect
counseling
Any society is not homogeneous
Families come from a variety of ethnic
backgrounds. The importance of the extended
family's involvement in the decision-making
process of a young immigrant couple may demand
that counseling sessions involve all appropriate
family members.
Soicio economic status influences a
family's access to medical services and their
understanding of the information presented

Providing non-directive counseling.
The family needs support for its decision and full
disclosure of options, but not paternalistic
counseling.
A useful method involves using the example of
other families but attaching no increased value to
a particular option
(e.g, " Some families choose prenatal diagnosis,
whereas others feel that insemination by donor is
the method for them ").

 Helping the family relieve feelings of shame and guilt
 The counselor may become a figure of authority, especially
early in the process of diagnosis, by stating that a particular
condition" is not their fault" Later, the family member may
remember this reassurance with comfort.
 Directly addressing feelings and normalizing them by comparing
the family positively to others in a similar situation may help.
 Parents' sense of responsibility for a child's problem may be
reframed as. " Its normal to feel responsible and to worry and
care about the child, without placing blame for the problem.
 Helping the parents to define which aspects of their child's
condition they control and which aspects are beyond their
control gives them a way to feel more positive.
 Recognizing the need for respite and encouraging such relief can
enable a family to deal better with the situation.

Helping the family identify its personal goals.
 Asking the family its expectations of the counseling session
helps to set the agenda and allows the counselor to address
additional issues. Families may not understand the purpose of
counseling and may feel responsible for" causing such a the
condition.
 a. Goals are often time-related, with an early goal being to
understand the medical implications and a later goal to decide
on another pregnancy.
 b. In this way, the family is helped to formulate the task
before them, given the pertinent information and support, and
then given the freedom to choose for themselves.

Recognizing counselor biases.
 It may be disappointing or frustrating that a family
makes choices against the advice of the counselor.
 One way to ensure that a couple decides for themselves
is to explore their opinion regarding the issues in a non-
judgemental manner.
 The counselor may list options regarding prenatal
diagnosis in a pregnancy in no particular order and
emphasize that different families choose different
options.

Follow-up of genetic counseling.
 It is unlikely that a family will clearly understand and be able
to use all of the information presented in a counseling
situation.
 Anxiety, grief, and fear may interfere with the process of
information exchange.
 A review counseling session - follow-up telephone call, or a
review letter to the family may be helpful. Pamphlets and
brochures regarding the specific diagnosis or introduction to
support groups provides additional information that may be
read or discussed after session.
 The additional contact also reinforces the clinic's interest in theGenetic counseling 68

PROBLEMS IN COUNSELINGPROBLEMS IN COUNSELING
Genetic Heterogeneicty
Phenocopies mimic genetic disorders
Sporadic case is common in nuclear families
Non Paternity or questioned paternity may
invalidate the risk quoted in a counseling
session.

Genetic heterogeneity
Often complicates the establishment of a precise diagnosis.
Similar disorders caused by mutations at different loci or
involving different alleles may have different forms of
inheritance.
Ex: Retinitis pigmentosa may be inherited as an autosomal
recessive or dominant condition, as well as an x-linked
condition.
Phenocopies mimic genetic disorders
Caused environmental factors, and are, therefore, unlikely
to recur.
Microcephaly may have both genetic and nongenetic causes.

Sporadic case is common in nuclear
families.
Here, the pedigree is, not helpful, and the counselor
must depend on an accurate diagnosis.
The advent of molecular methods of diagnosis has
helped in some areas (e.g., Duchenne muscular dystrophy
(DMD) with an identified deletion) to define a recurrence
risk for the family.
Non-paternity or questioned paternity may
invalidate the risk quoted in a counseling
session. Interpretation of molecular analysis is dependent
upon known paternity, with the use of both direct and
indirect methods.
The inadvertent discovery of non-paternity during the
course of such testing creates ethical concerns regardingGenetic counseling 71

GENETIC SCREENINGGENETIC SCREENING
Genetic screening is the identification
of a genetic disease, a genetic
predisposition to a disease, or a
genotype in an individual that
increases the risk of having a child
with a genetic disease.

Purpose of genetic screeningPurpose of genetic screening
Identifying individuals with a genetic disease
Identifying individuals at increased risk of
having children with a serious genetic disease
Identifying individuals with a genetic
predisposition to a disease.

Purpose of Identifying individuals
with a Genetic disease
To permit management of the disease or the
complications of the disease in a more effective
manner than would otherwise be possible.
Eg:
 Screening for Phenylketonuria in newborn
infants.
 Serum triple marker screening of pregnant
women for Down Syndrome.

Purpose of identifying individuals at
increased risk of having children with a
serious genetic disease
To permit them to take advantage of
reproductive options that may prevent the birth
of affected children.
Ex:
◦ Detection of heterozygous carries for Tay- Sachs
disease among Ashkenazi Jewish populations.
 Identification of couples in which both partners are
heterozygous carriers of Tay-Sachs disease permits them to
avoid having affected children
 Such couples may choose to do so by not having children
of their own, by having children via artificial insemination
from an unrelated donor, or by using prenatal diagnosis
with abortion of affected pregnancies.

Purpose of identifying individuals
with a genetic predisposition to a
disease
To enable them either to institute measures
that will prevent or delay development of
the disease or to deal with the disease more
effectively if it do develop.
This kind of screening, is called
Predictive testing.

Criteria forCriteria for ScreeningScreening
 There are thousands of genetic disease, but screening is
used routinely for only a few, given in Genetic screening
is usually undertaken only when certain conditions
relating to the disease, the screening test, and the system
for implementing them are met.
 Population Screening for Genetic Diseases and Carrier
States
◦ Characteristics of disease
◦ Characteristics of test
◦ Characteristics of screening system.

Individual with Genetic Disease
 Newborns
◦ Congenital hypothyroidism Phenylketonuria
◦ Sickle cell disease
 Fetuses
◦ Down syndrome
◦ Neural tube defects
 Heterozygous Carriers (in High -Risk
populations)
◦ Sickle cell disease (African- Americans and
Africans)
◦ Tay- Sachs disease (Ashkenazi Jews)
◦ α - Thalassemia (chinese, Southeast Asians)
◦ β- Thalassemia (Greeks, Italians).Genetic counseling 78

Characteristics of the disease
 Disease should be relatively frequent within the
population screened.
 More frequent the disease, the more effective will be
the screening program.
 Disease must produce severe impairment or death.
Ex: Screening for a trivial genetic condition such as post
minimal polydactyly- produces a tiny extra digit, could
not be justified because it can be safely and inexpensively
treated and produces no long -term morbidity.
 Some beneficial intervention must be possible if the
condition is recognized. This intervention is usually an
effective treatment or prevention strategy

Some conditions -
Sufficiently common Warrant screening in everyone
-Population screening.
Diseases are not common enough to
justify screening the entire population
Sufficiently frequent within an easily
identifiable subgroup.
Ex
Tay-Sachs disease - Ashkenazi Jews,
sickle-cell disease - African-
Americans, α- thalassemia - Southeast
Asians.
Many uncommon disease Justified only within families in which
an affected individual has been born.
Ex: Down syndrome

Characteristics of the test
An appropriate test must exist that
is capable of identifying people who have
relevant condition.
Appropriate tests should be highly
sensitive and specific, have reasonably
high positive value, and be relatively
inexpensive to perform.

Sensitivity Proportion of individuals with
disease
False Negative results
Good test will have low
frequency of false negatives
Specificity Proportion of individuals who are
unaffected by disease
False Positive
Good test will produce few false
positive.
Sensitivity and specificity bear a reciprocal relationship to each other. When
one is increased, the other decreases, and vice versa.
Thus setting cutoff levels for a screening test usually involves finding an
appropriate balance between sensitivity and specificity.
Positive
Predictive
value
Proportion of persons with a
positive test who actually have the
disease or genotype being tested
for
Higher the positive predictive
value, the lower the proportion of
false positives.
Expense Test applied to large populations
are usually less expensive to
perform if automation is possible
Economy is achieved by
combining more than one
screening test.
Ex: PKU and Hypothyroidism

Characteristics of the screening
system
Effective genetic screening requires the
use of an appropriate test within the
context of a well-organized and
comprehensive program for dealing
with abnormal results.

These must be prompt initial
testing and follow-up
A mechanism must exist to assure that
abnormal results are acted upon
quickly and appropriately.
An ongoing mechanism for
determining the effectiveness of the
screening program must be
instituted
Although a test may be theoretically
valuable. Its usefulness must be
demonstrated in practice and must be
continually reassessed in the face of
changing technology and demographics.
Education regarding the nature,
usefulness, and limitations of the
screening program must be provided
to physicians and other health care
professionals
Public knowledge regarding the
screening should be maintained,
particularly within the groups for whom
the screening is intended.
Benefits of the screening program
taken as a whole should exceed its
costs.
There should, at the least, be a favorable
economic benefit-to-cost ratio; social
and political costs and benefits must be
considered as well.

Genetic screening is usually a multi-stepGenetic screening is usually a multi-step
process.process.
 To avoid false- negative, screening tests frequently
produce a substantial number of false-positive results.
◦ a. In such circumstances, all patients who have a positive
result on initial screening require a more definitive test to
confirm that they exhibit the condition or genotype of
interest.
◦ b. A good example is provided by serum triple screening of
pregnant women for Down syndrome fetuses.
1) Most women with abnormal triple screening tests are
not carrying a fetus with Down syndrome (i.e. most
positive triple screening tests are false-positives).
2) Additional testing by ultrasound and amniocentesis is
required to distinguish true- positive from false-positive
results.

Concentrating genetic testing in
certain sub-populations
known to have a higher frequency of the
condition than the general population can be
thought of as initial screening that precedes the test
in some cases.
Ex: Thalassemia in much more common among
some ethnic groups (e.g., Italians, Greeks, and
Africans) than among others.
Performing genetic only in high-risk
ethnic groups increases the efficiency of testing.

Screening is often most effective when
information obtained from various sources is
combined to determine the result.
Ex: Risk of Down syndrome in the fetus of a
woman with an abnormal serum triple screen
depends on
◦ Absolute values obtained in the test
◦ Women's ethnic origin
◦ Gestational age
◦ Her weight
◦ She has diabetes.
All of these factors can be included in a single
risk estimate.

Ethical and Legal Concerns RegardingEthical and Legal Concerns Regarding
Genetic ScreeningGenetic Screening
 Although genetic screening programs are developed to
benefit patients and families, they sometimes have a
negative impact on screened populations.
Ex: People found to have a certain disease or genotype
have sometimes been stigmatized so that they are unable to
obtain employment or insurance.
 Education, both professional and public, is the most
important tool in preventing stigmatization.
 Genetic screening may be mandated by legislation,
which can raise issues of personal conscience, privacy, and
consent.

Future perspective: the genetic profileFuture perspective: the genetic profile
Recent advances in molecular genetics -have
increased the ability to identify individuals who
have genotype that produce disease.
Predicting most of the diseases that each
individual is likely to develop or pass on to his or
her children should be possible if advances in
genetic research continue.

Such knowledge would enable patients to:
 Alter their lives to reduce non-genetic risk factors of
particular relevance and thereby forestall the diseases to which
they are genetically predisposed.
 Take advantage of all available reproductive options if
potential offspring carry genetic risks.
 Privacy -Appropriate safe-guards will be necessary to make
certain that knowledge of a person's genetic endowment is
maintained with strictest confidentiality and does not result in
discriminatory practices against him or her.
 When a sufficiently large number of genotypes can be
identified, every individual will be found to carry some
disease-predisposing traits. Genetic counseling 90

Thus, genetic screening will be used
to determine the individual genetic
predispositions of every person
rather than to identify “normal" or
"abnormal" people.

Genetic counseling is the most
immediate and practical service that
genetics can render in medicine and
surgery.
There are two types of genetic counseling
Prospective
Retrospective

Prospective genetic counseling:
This allows for the true prevention of disease.
This approach requires identifying heterozygous
individuals for any particular defect by screening
procedure and explaining to them the risk of
their having affected children if they marry
another heterozygote for the same gene.

Application in this field
Ex: Sickle cell anemia and Thalassemia.
It also find wider application to cover a number of other
recessive defects.
Less common compared to retrospective counseling.
Importance should be given on psychological
effects and social pressure that may be brought
to bear on an individual so identified
Early stages of such programmes should include
intensive study of their psychological and social
implications. Genetic counseling 94

Lack of proper education it might result in
stigmatization of heterozygote’s, as though they
had a disease.
Heterozygote’s comprise a large fraction of the
population of many countries and they might
run the risk of becoming neurotic of being
refused life insurance or of being considered
undesirable marriage partner.

It is important to stress that trait alone is
of no clinical importance but if both the
marriage partners happens to affected with a
common gene then it is of significance.
No large scale programmes of population
screening for genetic counseling purposes have
been evaluated. The establishment of such
programmes is more complex. It is necessary
to provide laboratory testing centres.

Testing must be accompanied by preliminary
education of the population at risk &
appropriate services to follow up the result &
screening for heterozygotes.
Educational measures to be encouraged, it
includes an explanation of the simple genetic
facts of these diseases in schools, youth groups,
churches, social services and clubs through
radio, television, film strips and specially
prepared educational material.

Identified trait carriers need to be able to turn
to special clinics with centers for further advice
including counseling.
The most appropriate group to be screened for
genetic counseling purposes are children aged
12-15 years. For whom counseling would be
centered in schools.
All mothers admitted for delivery to maternity
hospitals are a captive group of prospective
testing followed by testing of the husbands in
order to identify risk

Retrospective genetic counseling:
Counseling the individuals who are known
carriers is known as retrospective
counseling.
The carriers are usually identified through an
affected child or other near relative in which case
it is termed as retrospective genetic
counseling.

It is a medical obligation to explain to the
parents the genetic mechanisms and to be
frank about the risk of recurrence.
In many cases the diagnosis is
established late in childhood when the
parents may already have had other
children.

Ideally both parents should be called
in for genetic advice and an
explanation of the genetic facts
must be given.
After full explanation the decision
whether to have further children
should be left to the parents. One
must make sure that the information is
properly assimilated.

The choice of the method for preventing the
recurrence of a genetic disorder depends in
its recurrence rate & severity as well as on
the attitudes and cultural environment
of the couples involved.
The method must be acceptable to the
couple and their society in accordance with
the customs & laws of their country with
these considerations and restrictions in mind
some of the preventive methods could be
suggested.

1. Contraception
2. Pregnancy termination
◦ This is carried or considered cases where advice is
sought after the women has become pregnant.
◦ Termination if found necessary is acceptable and legal
in several countries in the first months of pregnancy
◦ Legal limit varies from country to country.
3. Sterilization:
◦ Procedure is performed at the request of either the
husband or the wife.
◦ Most radical method of contraception and is
irreversible in most cases.
◦ Usually requested only when there is a high recurrence
rate for a severe genetic disorder. It should be
discouraged in young couples who may in future
decide to change their marital partner or resort.

A person may also undergo genetic counseling
after the birth of a child with a genetic condition.
In these instances, the genetic counselor explains
the condition to the patient along with recurrence
risks in future children.
In all cases of a positive family history for a
condition, the genetic counselor can evaluate
risks, recurrence and explain the condition itself.

Organization of Genetic counselingOrganization of Genetic counseling
Organization of genetic counseling and prenatal diagnosis differs
in various countries in the world
Netherlands-
Both Genetic counseling and prenatal diagnosis are concentrated
in few centers
Health insurance doesnot pay for activities outside these centers

Germany-
Genetic counseling and prenatal units exist in all
university institutes of human genetics
There are about 30 such units for a population of more
than 80 million
In addition qualified doctors are permitted to perform
genetic counseling and or certain routine genetic
diagnostics test, which therefore tend to be shifted from
university institutes to private practice.

Unites States
Genetic counseling and prenatal centers exist in most
medical schools as well as in many larger hospitals
Counseling prior to routine prenatal diagnosis is usually
performed by obstetricians.
Counseling for other than routine indications is usually
performed by qualified medical geneticists and
increasingly by genetic counselors, who have been
trained in human and medical genetics and its practical
applications for 2 years following 4 year college
education.

 Genetic counselors usually work in centers with a team that
includes
◦ Medical geneticists (Phd level)
◦ Biochemical and molecular geneticists (Phd level)
◦ Cytogeneticists (Phd level)
 Today growing proportion is attached to HMO’s and
obstetricians and Pediatricians
 These new professionals have filled an important gap in the
provision of genetic services, particularly to population
groups which because of geographic location and other
reasons have not access to expert genetic advice.

IndiaIndia
Genetic Centers in India.
 Department of Genetic Medicine -Sir Ganga Ram Hospital
Old Rajinder Nagar, New Delhi-110060 New Delhi
 Center for Genetic Disorders, Department of Human
Genetics, Guru Nanak Dev University, Amritsar, Punjab.
 Department of Human Genetics and Anatomy, St. Johns
Medical College, Bangalore.
 Department of Pediatrics, K.E.M. Hospital, Mumbai.
 ICMR Immunohematology Center, KEM Hospital. Mumbai.
 ICMR Genetic Research Center, Indian Council of Medical
Research, Wadia Hospital for Children, Mumbai.

 Department of Genetics, Ramakrishna Mission Hospital,
Calcutta.
 Departments of Pediatrics and Hematology,
Postgraduate Institute of Medical Education and
Research, Chandigarh.
 Genetics Unit, Department of Pediatrics, All India
Institute of Medical Sciences, New Delhi.
 Department of Medical Genetics, Sanjay Gandhi Post
Graduate Institute of Medical Sciences, Lucknow.
 Department of Genetics, Instiute of Child Health and
Institute of Obstetrics and Gynecology, Chennai.
 Genetics Center, Department of Pediatrics, B.J. Medical
College, Pune.

 It has been recommended that one genetic and
prenatal diagnosis unit should serve a population of a
million.
 Location in or affiliation with a university hospital
is a frequent and useful arrangement.
 Several medical geneticists, ideally with different
special knowledge in various subareas of medical
genetics and various clinical specialties, are desirable
 Non doctoral genetic counselors or specially
trained nurses are needed to deal with the many
problems of patient communication and follow up.

 The World Health Organizations Human Genetics
encourages health professionals to use these resources
for personal and professional growth. We aim to support
an educated and informed health workforce to provide
the best health services to populations worldwide and to
achieve the best possible health for all.
 Higher educational resources
Distance learning
Online self-training tools
Advanced degree courses
Continuing education for health professionals
Continuing education for nurses
Research and fellowship opportunities
Conferences and meetings

 Advanced degree courses
 Doctorate Courses (Italy/ India)
The International Centre for Genetic Engineering and
Biotechnology offers Ph.D. courses in Italy and in India.
Depending on the course, the duration ranges from three
to four years, and is completed in conjunction with
various institutions in those countries. This program has
a particular emphasis on helping developing countries.

 Research and fellowship opportunities
 - Short-Term Fellowship Programme (Italy/ India)
This programme is an establishment of the International Centre for
Genetic Engineering and Biotechnology, and is a three-month
maximum appointment. The appointment is either at the ICGEB
centres in Italy or India, or in one of the affiliated institutions.
- Post-Doctoral Fellowship Programme (Italy/India)
The International Centre for Genetic Engineering and
Biotechnology offers post-doctorate fellowship programmes to
individuals from its member states. The fellowship is offered either
in the ICGEB center in Italy or in India, and in some institutions in
Italy.

Quality ControlQuality Control
 For genetic counseling is more difficult but requires that
personnel engaged in this practice must have undergone
supervised training and ideally certification by
examination.
 This is available in US where a specialty board of medical
genetics exists for clinical genetics as well as for several
aspects of laboratory genetics
 Primary care providers: Pediatricians, obstericians,
pediatricians, and oncologists will require more training in
genetics and genetic counseling in medical schools and
during postgraduate training in order to advise patients
about the meaning and interpretation of many new genetic
tests that are becoming available.

Public Health or CommunityPublic Health or Community
GeneticsGenetics
 In recent years, however, emphasis has shifted toward
studies on clinically healthy persons, individual
differences in disease susceptibilities and appropriate
diagnostic and preventive measures in normal
populations.
 Conferences are being held that center around these
problems and new journal Community Genetics has
been founded.

L.P. Ten Kate in 1998 described these
problems as
 Community genetics……encompasses all activities to
enable the identification of people… with increased
genetic risk who want to acquire this knowledge in order
to make informed decisions. It minimizes the number of
people who would like to know that they are at
increased risk, but do not know yet. However, we should
not bargain on ethical principles of autonomy, doing
good and not harm, justice and providing equal access
and solidarity.

CONCLUSIONCONCLUSION
Genetic counselors provide supportive
counseling to families, serve as patient
advocates and refer individuals and families
to community or state support services.
They serve as educators and resource
people for other health care professionals
and for the general public.

Some counselors also work in
administrative capacities. Many engage in
research activities related to the field of
medical genetics and genetic counseling.
The field of genetic counseling is rapidly
expanding and many counselors are taking
on "non-traditional roles" which includes
working for genetic companies and
laboratories.

A survey carried by WHO showed that genetic
advice was chiefly sought in connection with
congenital abnormalities, mental
retardation, psychiatric illness and inborn
errors of metabolism and only a few
sought premarital advice.
WHO recommends the establishment of
genetic counseling centers in sufficient
numbers in regions where infectious disease and
nutritional disorders have been brought under
control and in areas where genetic diseases have
always constituted a serious public problem.

Genetic counseling comes under primary
level of prevention it is a type of
health promotional measure.
Optimum genetic counseling requires
an informed population and
dissemination of the facts in schools
and by the man media is strongly
recommended before population or
prospective counseling programmes are
initiated.

REFERENCES
 Preventive and Social medicine- Park- 19th
edition
 Oxford book of Public Health- Human and Medical
Genetics
 Shubha@sgpgi.ac.in
Department of Medical Genetics, Sanjay Gandhi Post
Graduate Institute of Medical Sciences, Raebareli Road,
Lucknow 226 014, India.
 www.indianpediatrics.net
 Phadke SR. Genetic counseling. Indian J Pediatr
2004;71:151-6

 Baker DI, Schutte JL, Unlamann WR. A Guide to
Genetic Counseling. Wiley Liso Publications, New York
1998;
 Biesecker BB, Peters KF. Process of studies in genetic
counseling; peering into the black box. Am J Med Genet
2001; 106: 91-198.
 Buyse ML. Birth Defect Encyclopedia. Blackwell
Scientific Publication, Inc, Oxford, 1990.
 Interactive Genetic Counseling Role-Play: A Novel
Educational Strategy for Family Physicians.
 Blaine SM, Carroll JC, Rideout AL, Glendon G,
Meschino W, Shuman C, Telner D, Van Iderstine N,
Permaul J.
J Genet Couns. 2008 Jan 30

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