Lecture 18 Flashcards
Prenatal Screening and Diagnosis
Screening(low risk testing) for and diagnosis of genetic and congenital disorders(previous child with goncgenital disorder/chromosomal abnormality) (or high risk group) in established pregnancies (single jean disroder running through familt)
Guides family in decisions about the pregnancy
-might involve termination of pregnancy
-facilitate medical and psychological support
Majority of testing normal, provides reassurance
38year old female, 8 weeks pregnant, concerned about risk of having children with down symdrome
increasing maternal ages past 35, significant increase in risk of down syndrome
What advice should be given to this patient? -increasing age, increasing risk 0.8-1% chance
What strategies can be used to predict risk?
What prenatal screening or diagnostic procedures are available? Non-invasive screening tests(ultrasound), maternal serum testing. Can have more directive diagnositic test
Should these procedures be offered?
A couple have a son with severe haemophilia (an X chromosomes linked clotting disorder). They wish to have another child, but would not consider this if there was a risk of a second haemophiliac child
Single gene disorder
Haemophilia: coagulation disorder, deficiency in clotting factor 8
X chromosomes so does effect both females and males
mother carrier
What options are available to this family?
Risks: male 50% risk
female: not affected. but 50% chance of being a carrier
CV/amniocentesis –> test DNA of fetal cells –> potentially PGD (mutation dependant and timing)
Prenatal testing
Screening tests:
-assess risk but no definitive diagnostic test e.g. maternal serum testing for down syndrome
-non-invasive, low risk tests
-commonly used in pregnancies
Diagnostic tests:
-where test for a specific chromosomal or genetic abnormality e.g. gene mutation analysis for cystic fibrosis
-invasive test, carriers some risk(fetus)
-commonly have fetal cells/DNa, look specifically at gene
Clinical indications for Prenatal Testing: Single gene disorders
Single Gene disorders:
-Family history (autosomal or X-linked)
-both parents carrier e.g. cystic fibrosis
-female carrier e.g. haemophilia (X-linked)
-one parent has an autosomal dominant disorder
Only consider if serious genetic disorder- cystic fibrosis/severe haemophilia (e.g. not haematomacrosis autosomal recessive disorder of iron over efficiency 1/10 caucasian carriers. Very treatable non life threatening disorder if recognised early and treated correctly)
Clinical indications for Prenatal Testing: Considered at risk for constitutional/congenital chromosomal disorder
Considered at risk for constitutional/congenital chromosomal disorder
- older mother pregnant (most common)
- previous child with significant developmental or other disorder
- exposure to chemical or toxic agent
- abnormal screening test result
Screening occurs when either:
- Family history of single gene disorder
2. High suspicion of a significant chromosomal disorder
Screening strategies: Ultrasound scan of pregnancy
Ultrasounds scan of pregnancy
- at 8 weeks to check dates, confirm number of babies
- at 18 weeks detailed scan for abnormalies can be done e.g. anencephaly, cardiac abnormalities
- safe procedure- no risk to mother or fetus
Screening strategies: Nuchal Translucency
(chromosal abnormalities/high risk mothers)
-thickness of neck
Nuchal Translucency
-measure by ultra sound 10-13 weeks pregnancy
-non-invasive test
-combine with maternal serum testing to increase sensitivity and specificity for Down syndrome screening (increased nuchal translucency in trisomy 21)
-combine with maternal age and blood test to give risk prediction
Screening strategies: Maternal Serum Testing
Maternal Serum Testing
- incongunction with maternal age and ultrasound
- performed at 15-17 weeks
- test for 2-4 feto-placental proteins e.g. AFP, Beta-hCG, unconjugated estriol (uE3), Inhibin A and pregnancy associated plasma protein A (PAPP-A)
Risk prediction for down syndrome
Screening in the second trimester by maternal age and maternal serum testing can identify 50-75% of trisomy 21 pregnancies with a false positive of 5%
Screening for fetal NT in the first trimester and maternal serum biochemistry in the second trimester reported a detection rate of trisomy 21 of 85-90% with false positive rate of 5%
–> May lead to specific diagnostic test e.g. amniocentesis and karyotype analysis (look at fetal cells, and do FISH of karyotype analysis to confirm if pregnancy is affected by downsyndrome or not)
(screening test –> leads to more definitive diagnostic test)
Single gene disorders
Risk prediction from analysis of pedigree
May proceed to specific diagnostic test if requested by the family
(cystic fibrosis)-autosomal recessive
Diagnositic Tests
Chorionic Villus Sampling
Amniocentesis
-Obtain fetal cells for further analysis (e.g. karyotype, FISH studies or single gene mutation analysis (hemophilia or cystic fibrosis mre specific)
Chorionic Villus Sampling
CV sampling
10-12 weeks of pregnancy (earlier)
Ultra sound guidance/transvaginal biopsies part of chorionic villus
Obtain fetal cells - analyze chromosomes or DNA
(throng of tissue allows for good cell counts and good yeild of tissue and DNa)(biochemical/genetic tests and karyotyping)
Risk of miscarriage approx 1% (invasive) -must be discused
Aniocentesis
Amniocentesis
15-16 weeks of pregnancy (later)
Ultra sound guidance/transabdominal
collect amniotic fluid which contains fetal cells
(centrifugation, biochemical/genetic tests and karyotyping)
may need to culture cells before analysis (usually for a week to get sufficient cells-delay-lengthier process)
miscarriage risk approx 1%