This document discusses prenatal genetics counseling and testing. It covers assessing risk factors like maternal age and family history. Common screening tests like maternal serum screening and ultrasound are described. Specific genetic disorders are reviewed including autosomal dominant, recessive, and X-linked conditions. Ethnic backgrounds that confer higher risk for certain disorders are noted. The document also discusses new developments in prenatal screening technologies.

1. Prenatal Genetics Owen Phillips, MD Reproductive Genetics

2. Objectives: Predicting fetal health as it pertains to genetic issues 1. Learn counseling issues concerning family history 2. Understand forms and indications for prenatal testing and screening

3. 3% of all babies- major congenital anomaly. Causes of birth defects: Genetic factors– 14% Environmental factors- 7% Multifactorial (combination of 1 and 2)- 25% Unknown etiology- 54%

4. Patient (Reproductive) History Previously affected offspring Stillbirths Spontaneous abortions Infertility and ART Teratogenic exposure Pedigree

5. Risk Factors for Offspring with a Chromosome Abnormality Maternal age (>35) Previous affected (1-2%) Maternal serum screening Ultrasound findings Specific risk depends on abnormality Carrier of chromosome rearrangements Most ascertained because of spontaneous losses

6. Counseling Purposes, potential results and the implications of results Routine genetic screening is routinely offered , not routinely performed Tests should not be performed without the knowledge of the patient

8. Amniocentesis > or = 14 weeks gestation Loss rate 1/1000 above baseline risk Infection/injury to fetus- <1/1000 Accuracy > 99.5 % detection rate chromosome abnormalities

9. Amniocentesis

11. First-trimester Prenatal Diagnosis Alleviate stressful aspects of prenatal testing Provides privacy concerning pregnancy management decisions Safety of first- versus second-trimester termination Testing must prove to be safe and accurate as traditional amniocentesis.

12. CVS Transcervical

13. CVS Transabdominal

15. Summary of CVS In experienced hands, loss rate from CVS comparable to Amnio TC and TA CVS risks comparable Infection rate (1/1000) similar amniocentesis As accurate as Amniocentesis

16. Screening for chromosome abnormalities Second trimester- a blood test hCG, estriol, AFP 60% Down syndrome First trimester- U/S and blood test Certified sonosgrapher PAPP-A, hCG

18. Autosomal Dominant Disorders Adult polycystic kidney disease Achondroplasia Ehlers-Danlos sydrome, type 1 Familial hypercholesterolemia Familial colonic polyposis Huntington disease Marfan syndrome Myotonic dystrophy Neurofibromatosis Noonan syndrome

19. Autosomal Recessive Disorders Alpha-1-antitrypsin deficiency Congenital adrenal hyperplasia (21-hydroxylase deficiency) Cystic fibrosis Homocystinuria Meckel-Gruber syndrome Thalassemia (alpha and beta) Phenylketonuria Refsum disease Sickle cell anemia Tay-Sachs disease Wilson disease Hurler syndrome

20. X-Linked Recessive Diseases Duchenne muscular distrophy Hemophilia B Ehlers-Danlos syndrome, type V Hunter syndrome (Mucopolysaccharidosis II) Glucose-6-phosphate deficiency Fragile X Hemophilia A Lesch-Nyham syndrome

21. Family history of single gene defects Need information prior to pregnancy- specific disease Takes months + to define mutations Early prenatal diagnosis- may take weeks to make a diagnosis

22. Physician’s Concerns Family History of MR Ethnic background Ultrasound Findings Results of screening tests Teratogen exposure

23. Ethnic background Jewish Greek / Mediterranean African-American Asian

24. Ashkenazic Jewish Heritage “ Jewish panel” for carrier detection Tay-Sachs Canavan CF +/- non-classical Gaucher Bloom syndrome Nieman-Pick Familial Dysautonomia

25. Other Ethnicities Mediterranean Beta Thalassemia African American Beta Thalassemia Sickle Cell Asian-American Beta Thalassemia Alpha Thalassemia

26. The Future is Here All patients will be candidates for having information about their pregnancies Screening all low risk pregnancies Offered by various companies Impact? Candidates?

27. Microarray testing for 63 genetic disorders using 1755 unique probes

28. Drawbacks Cost ‘ Fishing’- parents may carry benign mutation Counseling to explain each disease to give a couple enough information Maybe in a certain setting with informed consent on the front end

29. Ultrasound to diagnose genetic disorders Specific findings associated with specific disease

30. Ultrasound is a genetic screening tool Fetal survey 16-18 weeks

33. Drugs and Chemicals Pregnant women take an average of 4 drugs during pregnancy 40% of these drugs are taken during the critical period associated with teratogenicity

34. Teratogenic agents Drugs and chemicals Infectious agents Radiation Other