PREVENTION

OF GENETIC
DISEASES
 WHY PREVENTION ?
 Morbidity and mortality
 Chronic nature, life long
suffering
 Lack of definitive treatment
 Drain health and financial
resources
 Adversely affect family and
social life
 PRIMARY

PREVENTION

SECONDARY TERTIARY
 MODES OF
INTERVENTION
 HEALTH PROMOTION
 SPECIFIC PROTECTION
 EARLY DIAGNOSIS AND
TREATMENT
 DISABILITY LIMITATION
AND REHABILITATION
 HEALTH

PROMOTI
ON
 EUGENICS
NEGATIVE
POSITIVE
 EUTHENICS
 GENETIC COUNSELING
PROSPECTIVE
RETROSPECTIVE
 OTHER GENETIC
PREVENTIVE MEASURES
CONSANGUINOUS MARRIAGES
LATE MARRIAGES
X-LINKED GENETIC DISEASE PREVENTION
 HEALTH EDUCATION
EUGENICS
Sir Francis Galton,
1883

Science of the
improvement of the
genetic endowment
of the human race by
better selective
breeding
NEGATIVE EUGENICS
discouraging or preventing carriers of undesirable genotypes and
sufferers of inheritable diseases from reproducing to reduce the
number of deleterious genes in the population
Marriage restrictions, Birth control, Forced sterilization, Forced
abortions, Infanticide, Genocide, Euthanasia, Immigration
control, Segregation (racial segregation, segregation of the ill
from the normal)
new cases of hereditary diseases will still continue to arise due to
fresh mutations and marital alliances between hidden carriers
(hereto zygotes) of recessive defects
POSITIVE EUGENICS
encouraging the carriers of desirable genotypes to
reproduce more often to increase the number of
desirable genes in the population
Forced pregnancies, Genetic screening, Prenatal care
for mothers, Reprogenetics, Designer babies by use
of genetic engineering
Application is difficult because –
-most socially valuable traits like intelligence,
positive character have a complex, multifactorial
determination, both genetic and environmental
-we cannot determine which gene we transmit to
our children
 EUTHENICS
Environmental manipulation
to provide a suitable
environment which will
enable the genes to
express themselves
readily and efficiently
that shapes our
personality and behavior.
Mutual interaction of
heredity and
environmental factors
GENETIC
COUNSELING
Genetic counseling is a
communication
process which deals
with the human
problems associated
with the occurrence or
risk of occurrence of a
genetic disorder in a
family
 REASONS TO SEEK
GENETIC
COUNSELLING
 For information about a genetic disease/birth
defect/developmental anomaly and genetic
testing, prevention and treatment
 Establish or confirm a diagnosis
 Assess recurrence risks for family members
 Make referrals to appropriate specialists
 Help in making decisions about reproduction
 Provide ongoing education and support and
management
PRECONCEPTIONAL
/
PRENATAL
 Family history of a genetic condition or developmental disability
or birth defect
 Previous child with a genetic condition or birth defect
 Abnormal prenatal test results
 Risks related to a suspected or known exposure to certain
medicines, x-rays, illness or infection (e.g. diabetes, rubella) ,
chemicals or physical agents or other potentially harmful agents
while pregnant.
 Couples who have trouble conceiving or had several miscarriages,
intrauterine deaths, still births or infant deaths or complications
during pregnancy like IUGR, Oligohydramnios
 Consanguinity, mother age more than 35 years at conception or
because they have been screened for carrier status
 When sex determination is warranted, given a family history of
sex-linked genetic disease
 PEDIATRIC/
ADULT

 Presence of a known or suspected genetic disorder,

birth defect or developmental delay of unknown
etiology or a family history of any of these
 Adult-onset chronic diseases of an unknown origin
e.g. dominant polycystic kidney disease, Huntington
disease
 Genetic testing for cancer predisposition, diabetes
predisposition etc.
 Primary and secondary amenorrhea, sterility,
anomalies in the genitals
TIME OF GENETIC
COUNSELING
PROSPECTIVE GENETIC COUNSELING
premarital – screening for hetero zygotes or healthy
carriers and preventing heterozygous marriage to
decrease the risk of their having affected
children. E.g. - sickle cell anaemia, thalassemia
Preconceptional - when there is a risk factor like
advanced maternal age
Prenatal – when tests reveal that the fetus is at risk.

RETROSPECTIVE GENETIC COUNSELLING

after the birth of an affected child
Methods suggested
depend on the
attitudes and cultural
environment of the
couples involved
-contraception
-pregnancy
termination
-sterilization
PROVIDERS OF GENETIC
COUNSELING
 Clinical geneticist
 Non-geneticist
physician
 Genetic counselor
 COMPONENTS OF
GENETIC COUNSELING
 Information gathering
 Establishing or verifying
diagnosis
 Risk assessment
 Giving information
 Psychological counseling
 Help with decision making
 Ongoing client support
 GENETIC COUNSELING
DIFFICULTIES
 Difficulties in getting family
history
 Infrastructure needed for
diagnosis and ongoing
client support
 Racial, cultural and ethnic
differences regarding
genetic testing – views,
beliefs, knowledge,
attitudes, values, behavior
 Concerns about privacy and
lack of trust in their doctors
 PROMOTION OF GENETIC
COUNSELING
 Giving priorities to
genetic disorders in
public health policy
 Population education
 Providing proper
genetic facilities
 Training of genetic
counselors
OTHER GENETIC
PREVENTIVE MEASURES
 CONSANGUINEOUS MARRIAGES –
increased risk in the offspring of
traits controlled by recessive genes
and polygenes E.g. albinism,
alkaptonuria, Phenylketoneuria,
increased risk of premature death
 LATE MARRIAGES – elderly mothers
above 35 years- increased
incidence of children with trisomies
like Down’s syndrome
 Avoid consanguineous and late
marriages
X – LINKED GENETIC
DISEASE PREVENTION
Couples with family
history of X -linked
diseases or who are
carriers of X- linked
disorders can have an
unaffected child by pre-
selecting the sex of the
child. Usually expressed
in the male offspring,
females are generally
unaffected.
 HEALTH EDUCATION
 educate people about genetic
diseases, counseling and prevention,
nutrition, healthy and safe
environment
 life style and behavioral changes
 Target groups – general public,
patients, at risk groups, health
providers, community leaders,
decision makers
 Cost affective public health
approaches
 mass media, Education of students
at different levels - school, college,
university.
 SPECIFIC

PROTECTI
ON
 Protection of individuals and
whole communities against
mutagens like X-rays and other
ionizing radiations, chemical
mutagens
 Protection of patients
undergoing X-ray examination
against unnecessary exposure of
the gonads to radiation
 Disapprove using X-ray
examination of the pregnant
uterus to determine the
presence of twins or lie of the
foetus
 Prevention of Rh haemolytic
disease of the newborn by
immunization by anti-D globulin
 EARLY
DIAGNOSIS
AND
TREATMENT
 DETECTION OF
GENETIC CARRIERS
 PRENATAL DIAGNOSIS
 SCREENING OF
NEWBORN INFANTS
 RECOGNISING
PRECLINICAL CASES
GENETIC TESTING TYPES
 Predictive / presymptomatic – detecting genetic
disorders or predicting risk of disease
development before clinical presentation in at risk
population. There will be ample time to intervene.
Disadvantage - adverse psychosocial
consequences for the individual and family,
possibility of discrimination
 Diagnostic – patient presents with clinical
features of a disease and DNA test is done to
confirm the diagnosis e.g. – DM, altered skin
pigmentation, and persistently increased ferritin
levels - haemochromatosis
GENETIC SCREENING
OBJECTIVES
 Identify individuals predisposed to genetic
disease so that they may receive intervention or
treatment e.g. – newborn screening programs
 Identify individuals at risk of having children
affected by genetic diseases e.g. - women > 35
years, family history
 Gather needed epidemiological information e.g. –
population screening
 SCREENING
GENETIC
TESTS
Family screening - testing in families where a disease
recurs to allow genetic counseling regarding
reproduction e.g. – normal siblings of patient with
sickle cell anaemia > 50 % chance of being carrier.
 Community screening - in special target groups. E.g.
1.Increased predisposition to a genetic disease due to
ethnic background e.g. thalassaemia in people of
Mediterranean origin, Tay –Sachs disease in Ashkenazi
Jews
2.If treatment or prevention is possible for a given
defect to establish a population-based prevention
program e.g. testing for haemochromatosis to prevent
the disease by prophylactic venesection
3.newborn screening program
DETECTION OF HEALTHY
GENETIC CARRIERS
To prevent carriers mating and
provide counseling e.g.
thalassemia trait
In some conditions
- carriers can be recognized
with a high degree of certainty
e.g. acatalasia
- only a proportion of carriers
can be detected e.g.
haemophilia, PKU,
galactosaemia
- no method to detect carriers
presently e.g. alkaptonuria
PRENATAL DIAGNOSIS
 Screening tests - Ultrasonography, blood tests
 Diagnostic tests - Chronic villus sampling (CVS) at 10
weeks of pregnancy, Amniocentesis after 14 weeks
 If the foetus is affected permits
- pregnancy termination
- in few disorders, therapy in utero or special
management during pregnancy/delivery to minimize
further damage e.g. foetus with methyl malonic
academia - mother given Vit B12, galactosemia -
mother given low galactose diet
INDICATIONS FOR
PRENATAL DIAGNOSIS
 screening report suggesting the possibility of a
genetic disorder
 Advanced maternal age or other risk factors like
exposure to harmful agents
 previous child or family history of genetic
disorders, birth defects, IUGR.
INVESTIGATIONS
 Sonography, Foetoscopy
 Amniotic fluid screened for
specific metabolites,
enzymes
 Chromosome analysis of
foetal cells obtained at
sampling
 Maternal serum screening
using biochemical markers
for conditions like neural
tube defects, Maternal
serum alpha feto protein
and chorionic gonadotropin
 AMNIOCENTESIS

amniotic fluid examination

1. chromosomal anomalies by culture and
karyotyping of foetal cells from amniotic fluid
2. some metabolic defects by biochemical
analysis of the fluid
3. Neural tube defects by elevation of alpha
feto protein in amniotic fluid
ROUTINE SCREENING
OF
NEWBORN INFANTS
Tests for common or preventable diseases that require
early treatment  Sex chromosome abnormalities

 PKU  Congenital dislocation of hip

 Galactosemia
 Congenital hypothyroidism
 Homocysteinuria
 Sickle cell disease
 Cystic fibrosis
 Maple syrup urine
disease
 Duchenne muscular dystrophy
 Tyrosinemia
 Congenital adrenal hyperplasia
 Thalessemia
 Tay - Sachs
 Niemann - Pick
 Gaucher Disease
 Familial
Hyperinsulinism
 Glycogen Storage
disorders
 G6PD deficiency
 Within 48 hours of a child's birth,
blood spot is obtained from a heel
prick on filter paper and is analyzed
for about 50 treatable diseases using
different methods e.g. Sickle cell
disease by Hb electrophoresis of
blood spots, Cystic fibrosis by
measurement of immunoreactive
trypsin in blood spots,
Phenylketoneuria by phenylalanine
levels
 Urine samples taken in first month of
life on filter paper screened for
inherited diseases of metabolism
 Diagnosis of mucoviscidosis by
chlorides levels in sweat
 Identified quickly, cheaply and
reliably. Early and easy treatment
NEWBORN GENETIC
SCREENING VS RIGHT TO
PRIVACY
 Weighs individual privacy rights
against public health
 Classic case of seen vs. unseen
 Visible results are measured in
children's’ lives
 Unseen unintended
consequences – psychological
risks, social stigma, insurance
and employment
discrimination, destruction of
blood samples after testing
 If not government then who?
 RECOGNISING
PRECLINICAL CASES
Screening tests for early diagnosis of hereditary diseases
 Hetero zygotes for Phenylketoneuria – phenylalanine
tolerance test
 Diabetes – urine examination for sugar after morning
breakfast
 Acholuric jaundice – examination of siblings and close
relatives of diabetics by glucose tolerance test
 Gout – raised serum uric acid
 Sickle cell trait – subjecting RBCs to reduced O2
tension
 Thalassaemia minor – studying blood picture
TREATMENT – MEDICAL
AND SURGICAL
PKU – diets low in phenylalanine
Hemophilia – administering antihaemolytic globulin,
which promotes blood clotting
Spina bifida – surgical techniques
Haemochromatosis - regular venesection
REHABILITATI
ON
 Combined and coordinated
use of medical, social,
educational and vocational
measures for training and
retraining the individual to the
highest possible level of
functional ability
 Medical – Minimizing mental
and physical disabilities,
restoration of function
 Vocational – Education,
restoration of capacity to earn
a livelihood
 Social – Restoration of family
and social relationships
 Psychological rehab –
Restoration of personal dignity
and confidence
COMMUNITY GENETIC
SERVICES
 Priority to genetic disorders in
health programmes
 Adequate, accessible,
appropriate and quality genetic
services
 Education and training for the
health care personnel, patients,
their families and the general
public
 Research to identify the
molecular pathogenesis of the
genetic diseases, establish more
definitive methods for the
diagnosis of genetic defects
 Identify means of prevention and
control incorporating field and
clinical trials