08.31.23 CM_Genetic Testing in Pregnancy_Al-Kouatly_Notes.pdf

August 31, 2023 Genetic Testing in Pregnancy Page 1 of 4 Genetic Testing in Pregnancy Instructor: Huda B. Al-Kouatly, MD ([email protected]) Block 5: Urology/Endocrine/Reproduction Thread: Clinical Medicine Conflicts of Interest: None Learning Objectives: By exam time, you should be...

August 31, 2023 Genetic Testing in Pregnancy Page 1 of 4 Genetic Testing in Pregnancy Instructor: Huda B. Al-Kouatly, MD ([email protected]) Block 5: Urology/Endocrine/Reproduction Thread: Clinical Medicine Conflicts of Interest: None Learning Objectives: By exam time, you should be able to: 1. Explain practice guidelines for screening for fetal aneuploidy. 2. Explain practice guidelines for prenatal diagnostic testing for genetic disorders. 3. Recongize the advantages and disadvantages of each screen and diagnostic test. 4. Discuss case examples. Study Questions: 1. What is the difference between genetic screening and genetic diagnostic testing and what are the test options for each of these? 2. Why should genetic screening and genetic diagnostic testing be offered to every patient/family? 3. How does cell-free DNA work? August 31, 2023 Genetic Testing in Pregnancy Page 2 of 4 Lecture Summary: Genetics screening should be offered to all pregnant patients regardless of age Genetics testing (CVS or amniocentesis) should be offered to all pregnant patients regardless of age The most common genetic abnormalities that affect pregnant patients < 35 years of age are not trisomy 21, 18 and 13. The most common genetic abnormality that affects pregnant patients < 35 years of age are deletions and duplications. The most common genetic abnormalities that affect pregnant patients > 35 years of age are trisomy 21, 18 and 13. MSAFP increased: Neural tube defects (NTD is a risk in maternal diabetes mellitus) Abdominal wall defects like omphalocele and gastroschisis Part 1 SS (first trimester screen): NT, HCG, PAPPA Part 2 SS (Quad screen): AFP, HCG, Estriol, Inhibin A Quad screen: AFP, HCG, Estriol, Inhibin A First Trimester screen Down syndrome: increased HCG, Low PAPPA First Trimester screen Trisomy 18: decreased HCG, Low PAPPA August 31, 2023 Genetic Testing in Pregnancy Page 3 of 4 Down Syndrome Quad screen: Increased HCG and increased Inhibin Decreased AFP and decreased estriol Trisomy 18 Quad screen: All are low No need to memorize any formula in lecture or risks of chromosomal abnormalities in any of the tables. Genetic screening at Jefferson: 1. Maternal age < 35 years: Sequential screen Part 1 and Part 2 2. Maternal age > 35 years: cfDNA plus MSAFP Study Question Answers 1. Q: What is the difference between genetic screening and genetic diagnostic testing and what are the test options for each of these? A: Genetic screening is used to assess risk of having a fetus affected by a common aneuploidy. Diagnostic testing is the direct evaluation of fetal DNA for the presence or absence of chromosomal differences, including chromosome number as well as duplications or deletions of fetal DNA. Diagnostic testing can also be used to test the fetus for specific genetic disorders, such as cystic fibrosis. Genetic screening tests include first trimester screen, sequential screen, triple screen, quad screen, and cell-free DNA screening. The sequential screen is just a combination of the first trimester screen and the quad screen (which is done in the second trimester). Nuchal translucency measurement is also used in genetic screening, as it can be thickened in some aneuploidies and/or structural abnormalities. Genetic diagnostic testing is done via chorionic villus sampling (CVS) between 10-13 weeks or amniocentesis between 15-10 weeks. The placental or fetal cells are then analyzed for aneuploidy, DNA deletions/duplications, and, if indicated, specific genetic disorders. 2. Q: Why should genetic screening and genetic diagnostic testing be offered to every patient/family? August 31, 2023 Genetic Testing in Pregnancy Page 4 of 4 A: Each patient/family has different goals and values. Patients should be told about the options for screening and testing so they can make the decision that best fits those goals and values. Some patients may feel comfortable with a low-risk screening test, while others may desire as much genetic information as possible through diagnostic testing. Some patients may continue a pregnancy with a genetic difference, while others may not. A patient may want to have a diagnosis to be prepared for possible newborn complications, while others may decide not to continue the pregnancy in the setting of known genetic difference. The bottom line is that this is a decision for each patient to make, and they should be aware of the options for screening and diagnostic testing. 3. Q: How does cell-free DNA work? A: DNA from apoptotic cells from both the fetus and the pregnant person can be found circulating in the bloodstream of the pregnant individual. The DNA from both the pregnant person and the fetus are sequenced together, understanding that about 10% of a typical sample is fetal. A difference in the expected amount of DNA from a particular chromosome may indicate an aneuploidy of that chromosome.