Genetic Counseling and
Prenatal Diagnosis
Dr. Hassan Nasrat
FRCS & FRCOG
Professor
Dept. Obstetrics & Gynecology
King Abdulaziz University Hospital
Obstetricians are increasingly encountering couples who
have worries about particular problem or disorder
It is essential then to understand:
 The various Methods used for prenatal screening and
diagnosis and their limitation.
 Adequate understanding of the basic principles of genetic
inheritance, gene structure and analysis.
Genetic Counselling
Genetics Consultation
Genetics consultation is evaluation of an
individual or family Member Regarding a
Genetic Disorder or Its Risk.
A genetics consultation involves the following:
 A genetic condition : To diagnose or rule out
 Calculating genetic risk ( i.e. probability of developing
and/or transmitting it)
 Discuss issues of medical management (consequences of this
disorder and ways in which the disorder my be prevented or
ameliorated)
 Providing or arranging for psychosocial support
INDICATIONS FOR GENETIC COUNSELING

A known or suspected hereditary disease in the patient or a family member
 Maternal age of 35 years or older during a pregnancy
 Teratogen exposure during pregnancy
 Ethnic background associated with an increased prevalence of a heritable
disorder
 Recurrent pregnancy loss
 Identification of abnormalities during an antenatal sonogram
 Abnormal results on first or second trimester screening test.
 Family history of early onset cancer
Important Issues in Genetic Counseling:
 The Genetic counseling make no directive suggestions.
 There is no “right” or “wrong” decision but the decision should
be the right one for the patient own situation.
 Success or failure should not be judged on terms of a particular
outcome.
 The family should be given support for whatever decisions they
may take.
Ethical and Legal Aspects of genetic testing on patients and other
family members.
Likelihood of developing the disease
In genetic counselling there is hardly yes or no
answer. Often information are given in terms of
probability or odds:
Risks and Odds:
What is the risk of a particular member in a family,
born or unborn, having or developing the particular
disorder?
Odds
Percentages
1 in2
50
3
33
4
25
5
20
30
3.3
100
1.0
Likelihood of developing the disease
• Empiric Risk:
Is based on observed data rather than on theoretical predictions. E.g. most
non-mendelian or chromosomal disorders.
The is further affected by:
- The accuracy of the diagnosis.
- The population being studied
• Mendelian Risk:
In case of single gene inherited disorders, whether a dominant, recessive or
sex linked disorder.
•Other Factors:
PENETRANCE (i.e. likelihood of developing disease given inheritance of diseasecausing mutation)
EXPRESSIVITY (i.e. phenotypic variations in the way the disease is expressed).
The recommendations are:
The woman improve her blood glucose level prior to
conception (ideally HbA1c less than 8 percent) to reduce
the risk of diabetic embryopathy.
We offered the couple genetic testing to identify mutations
that cause NF1 and XHED.
The information could then be used for preimplantation or
prenatal diagnosis (although in neither case would knowledge of the
mutation be likely to predict the severity of the condition in the fetus).
Prenatal Diagnosis
Prenatal Screening and Prenatal
Diagnosis
 Developments of New Methods for
Early screening.
 Developments of Tests for Fetal
tissue Sampling.
 Developments in the Technology of
Genetic Testing.
Prenatal Diagnosis
Techniques
Non-Invasive
Invasive
•Ultrasound Scanning
•Amniocentesis
•Biochemical Markers
•Chorion Villus Sampling
•Analysis of Fetal Cells
In Maternal Blood
•Fetal Blood Sampling
•Analysis Of Fetal Cells in
Transcervical Samples
•Fetal Tissue Sampling
• Pre-Implantation Diagnosis
Rationale for prenatal screening and
diagnosis
• Parental awareness
• Option of TOP
– Karyotype: 32%
– Structural: 68%
• Avoidance of inappropriate delivery/ resuscitation
• Optimal timing / mode / place of delivery
• In-utero therapy
• ?Reducing PMR, because of tops for fetal anomaly
Screening Tests
 To Identify A Specific Disease Among Asymptomatic
Individuals.
 Non Invasive.
 The Result Will Usually Changes ( Either or
)a
Woman Risk of Having a Baby With the Disorder.
 Targeted Screening: Is systematic testing of Selected
Group considered to be at High Risk .
Diagnostic Tests
 For A Specific Diagnosis In Patients Who Have
Actively Sought Health Care Or Following A
Positive Screening Test.
 Usually Invasive, Has A Measurable Degree Of
Risk For The Fetus.
 The Risk Of Doing The Test Should Be
Balanced against The Risk Of Having The
Disease.
Screening Tests
• Maternal Age.
• Biochemical Tests:
Maternal Serum AFP (e.g. For NTD and DS)
Triple Test 15-20 Weeks.
• Detailed U/S 16-18 Weeks.
• Fetal Nuchal Translucency Screening for DS.
• Fetal Cells in Maternal Blood.
Diagnostic Tests
•
Amniocentesis.
• Chorion Villus Sampling.
•
Fetal Blood & Tissue Sampling.
•
Fetal Cells in Cervical Brush.
Alternative Reproductive Options
•
Pre-Implantation Genetic Diagnosis
PGD .
Biochemical Screening tests
 Alpha Fetoprotein Screening for NTD
(AFP)
 Biochemical Markers for DS.
Biochemical screening
•
•
•
•
•
Free beta HCG
AFP
PAPP-A
Oestriol
Inhibin
2nd trimester
Factors Influence AFP
 GA: the level of AFP increase by about
15% per week.
 Maternal Weight:
 Race:
 IDD:
 Multiple Pregnancy:
 Family history of NTD:
Maternal Age as Screening for DS
 Women above 35 years has 1:250 risk of
having DS baby
 The risk of amniocentesis 1%.
 Only 5% of pregnant population are > 35
years of age.
 Not all of them accept amniocentesis
Thus only 30 % of DS are identified if age
alone is used as criteria for diagnosis
Screening Tests for DS
• Biochemical
– 1st trimester
• Quadruple blood test
– 2nd trimester
• Double, triple test
• Ultrasound
– 1st trimester
• The 11-14 wk NT scan
– 2nd trimester
• Routine anomaly scan
Integrated
• Combined
• Sequential
Biochemical Screening in Prenatal Diagnosis
Markers Values at 17 weeks
Actual
Gestation MOM
Risk at 17 wk.
Case AFP
uE3
hCG
1
0.5
0.5
2.0
1 : 28
2
0.5
1.0
1.0
1 : 280
3
2.0
0.5
0.5
1 : 2600
4
2.0
1.0
0.5
1 : 14000
Apparent Risk of DS using combination of markers for a
a woman at 37 years old
Wald & Cukle 1992
Ultrasound as a Screening for fetal
anomalies
ULTRASOUND
• Direct Visualization of the Malformation.
• Facilitate Other Diagnostic Techniques.
• Accurate Fetal Measurement to Maximize
performance of other Tests
 A ‘normal’ scans mean that no abnormalities
were observed.
 The ability to identify abnormalities depends
on several factors:
 Technical factors: The skill of the
sonographer the time available to perform the
scan and the quality of the equipment used.
 Biological factors: maternal size, fetal
position and age and amniotic fluid volume.
TV US during the 1st trimester showing measurement of fetal NT.
The cursors are placed on the inner aspect of the white line
describing the NT. The widest part of the neck should be
measured.
The NT scan
NT
Amniocentesis
CHORIONIC VILLUS
SAMPLING
CHORIONIC VILLUS SAMPLING
Cytotrophoblast
“ Mitotically active
, yield metaphase
spread for
direct exam.”
Syncytiotrophoblast
Inner Mesoderm
“ Require 7 -14 days
in culture”
Anatomy of Mature Placental Villi
Fetal Blood Sampling
Pre-Implantation Genetic
Diagnosis
PGD
Ethical Principle