Prenatal Genetics

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Prenatal Genetics

  1. 1. Prenatal Genetics Owen Phillips, MD Reproductive Genetics
  2. 2. Objectives: Predicting fetal health as it pertains to genetic issues <ul><li>1. Learn counseling issues concerning family history </li></ul><ul><li>2. Understand forms and indications for prenatal testing and screening </li></ul>
  3. 3. 3% of all babies- major congenital anomaly. <ul><li>Causes of birth defects: </li></ul><ul><li>Genetic factors– 14% </li></ul><ul><li>Environmental factors- 7% </li></ul><ul><li>Multifactorial (combination of 1 and 2)- 25% </li></ul><ul><li>Unknown etiology- 54% </li></ul>
  4. 4. Patient (Reproductive) History <ul><li>Previously affected offspring </li></ul><ul><li>Stillbirths </li></ul><ul><li>Spontaneous abortions </li></ul><ul><li>Infertility and ART </li></ul><ul><li>Teratogenic exposure </li></ul><ul><li>Pedigree </li></ul>
  5. 5. Risk Factors for Offspring with a Chromosome Abnormality <ul><li>Maternal age (>35) </li></ul><ul><li>Previous affected (1-2%) </li></ul><ul><li>Maternal serum screening </li></ul><ul><li>Ultrasound findings </li></ul><ul><ul><li>Specific risk depends on abnormality </li></ul></ul><ul><li>Carrier of chromosome rearrangements </li></ul><ul><ul><li>Most ascertained because of spontaneous losses </li></ul></ul>
  6. 6. Counseling <ul><li>Purposes, potential results and the implications of results </li></ul><ul><li>Routine genetic screening is routinely offered , not routinely performed </li></ul><ul><li>Tests should not be performed without the knowledge of the patient </li></ul>
  7. 8. Amniocentesis <ul><li>> or = 14 weeks gestation </li></ul><ul><li>Loss rate 1/1000 above baseline risk </li></ul><ul><li>Infection/injury to fetus- <1/1000 </li></ul><ul><li>Accuracy > 99.5 % detection rate chromosome abnormalities </li></ul>
  8. 9. Amniocentesis
  9. 11. First-trimester Prenatal Diagnosis <ul><li>Alleviate stressful aspects of prenatal testing </li></ul><ul><li>Provides privacy concerning pregnancy management decisions </li></ul><ul><li>Safety of first- versus second-trimester termination </li></ul><ul><li>Testing must prove to be safe and accurate as traditional amniocentesis. </li></ul>
  10. 12. CVS Transcervical
  11. 13. CVS Transabdominal
  12. 15. Summary of CVS <ul><li>In experienced hands, loss rate from CVS comparable to Amnio </li></ul><ul><li>TC and TA CVS risks comparable </li></ul><ul><li>Infection rate (1/1000) similar amniocentesis </li></ul><ul><li>As accurate as Amniocentesis </li></ul>
  13. 16. Screening for chromosome abnormalities <ul><li>Second trimester- a blood test </li></ul><ul><ul><li>hCG, estriol, AFP </li></ul></ul><ul><ul><li>60% Down syndrome </li></ul></ul><ul><li>First trimester- U/S and blood test </li></ul><ul><ul><li>Certified sonosgrapher </li></ul></ul><ul><ul><li>PAPP-A, hCG </li></ul></ul>
  14. 18. Autosomal Dominant Disorders <ul><li>Adult polycystic kidney disease </li></ul><ul><li>Achondroplasia </li></ul><ul><li>Ehlers-Danlos sydrome, type 1 </li></ul><ul><li>Familial hypercholesterolemia </li></ul><ul><li>Familial colonic polyposis </li></ul><ul><li>Huntington disease </li></ul><ul><li>Marfan syndrome </li></ul><ul><li>Myotonic dystrophy </li></ul><ul><li>Neurofibromatosis </li></ul><ul><li>Noonan syndrome </li></ul>
  15. 19. Autosomal Recessive Disorders <ul><li>Alpha-1-antitrypsin deficiency </li></ul><ul><li>Congenital adrenal hyperplasia (21-hydroxylase deficiency) </li></ul><ul><li>Cystic fibrosis </li></ul><ul><li>Homocystinuria </li></ul><ul><li>Meckel-Gruber syndrome </li></ul><ul><li>Thalassemia (alpha and beta) </li></ul><ul><li>Phenylketonuria </li></ul><ul><li>Refsum disease </li></ul><ul><li>Sickle cell anemia </li></ul><ul><li>Tay-Sachs disease </li></ul><ul><li>Wilson disease </li></ul><ul><li>Hurler syndrome </li></ul>
  16. 20. X-Linked Recessive Diseases <ul><li>Duchenne muscular distrophy </li></ul><ul><li>Hemophilia B </li></ul><ul><li>Ehlers-Danlos syndrome, type V </li></ul><ul><li>Hunter syndrome (Mucopolysaccharidosis II) </li></ul><ul><li>Glucose-6-phosphate deficiency </li></ul><ul><li>Fragile X </li></ul><ul><li>Hemophilia A </li></ul><ul><li>Lesch-Nyham syndrome </li></ul>
  17. 21. Family history of single gene defects <ul><li>Need information prior to pregnancy- specific disease </li></ul><ul><li>Takes months + to define mutations </li></ul><ul><li>Early prenatal diagnosis- may take weeks to make a diagnosis </li></ul>
  18. 22. Physician’s Concerns <ul><li>Family History of MR </li></ul><ul><li>Ethnic background </li></ul><ul><li>Ultrasound Findings </li></ul><ul><li>Results of screening tests </li></ul><ul><li>Teratogen exposure </li></ul>
  19. 23. Ethnic background <ul><li>Jewish </li></ul><ul><li>Greek / Mediterranean </li></ul><ul><li>African-American </li></ul><ul><li>Asian </li></ul>
  20. 24. Ashkenazic Jewish Heritage <ul><li>“ Jewish panel” for carrier detection </li></ul><ul><ul><li>Tay-Sachs </li></ul></ul><ul><ul><li>Canavan </li></ul></ul><ul><ul><li>CF </li></ul></ul><ul><ul><li>+/- non-classical Gaucher </li></ul></ul><ul><ul><li>Bloom syndrome </li></ul></ul><ul><ul><li>Nieman-Pick </li></ul></ul><ul><ul><li>Familial Dysautonomia </li></ul></ul>
  21. 25. Other Ethnicities <ul><li>Mediterranean </li></ul><ul><ul><li>Beta Thalassemia </li></ul></ul><ul><li>African American </li></ul><ul><ul><li>Beta Thalassemia </li></ul></ul><ul><ul><li>Sickle Cell </li></ul></ul><ul><li>Asian-American </li></ul><ul><ul><li>Beta Thalassemia </li></ul></ul><ul><ul><li>Alpha Thalassemia </li></ul></ul>
  22. 26. The Future is Here <ul><li>All patients will be candidates for having information about their pregnancies </li></ul><ul><li>Screening all low risk pregnancies </li></ul><ul><li>Offered by various companies </li></ul><ul><li>Impact? Candidates? </li></ul>
  23. 27. Microarray testing for 63 genetic disorders using 1755 unique probes
  24. 28. Drawbacks <ul><li>Cost </li></ul><ul><li>‘ Fishing’- parents may carry benign mutation </li></ul><ul><li>Counseling to explain each disease to give a couple enough information </li></ul><ul><li>Maybe in a certain setting with informed consent on the front end </li></ul>
  25. 29. Ultrasound to diagnose genetic disorders <ul><li>Specific findings associated with specific disease </li></ul>
  26. 30. Ultrasound is a genetic screening tool <ul><li>Fetal survey </li></ul><ul><ul><li>16-18 weeks </li></ul></ul>
  27. 33. Drugs and Chemicals <ul><li>Pregnant women take an average of 4 drugs during pregnancy </li></ul><ul><li>40% of these drugs are taken during the critical period associated with teratogenicity </li></ul>
  28. 34. Teratogenic agents <ul><li>Drugs and chemicals </li></ul><ul><li>Infectious agents </li></ul><ul><li>Radiation </li></ul><ul><li>Other </li></ul>

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