Gyula Richard Nagy: Genetic counseling
- 1. Genetic Counseling Gyula Richárd Nagy MD, PhD
- 2. Genetic counseling in obstetric care Historical stages of obstetric care - To avoid maternal death (eg. it was not obvious to suture the abdomen during cesarean section) - To avoid infant mortality - To prevent the birth of mentally and/or physically damaged newborns (we are still working on this)
- 3. Genetic counseling in obstetric care How can we fulfill these requirements? - Fetal medicine has been developed (The fetus is our „youngest patient”.) - With prenatal diagnostic methods we are able to examine the anatomy of the fetus (ultrasound, MRI); the chromosomes, genes, enzimes of the fetus (CVS, amnio, PUBS, cytogenetics, PCR, etc.)
- 4. Genetic counseling in obstetric care Four ways of preventing genetic diseases 1. To identify individuals as being at high risk of transmitting harmful genes (genetic counseling). 2. To avoid the preconceptional damage of gamete cells by reducing exposure to viruses, radiation, unnecessary medication. 3. Intensive use of prenatal or neonatal screening or prenatal diagnosis. 4. To offer induced abortion in incurable cases (genetic counseling).
- 5. Genetic Counseling Genetic counseling is a communication process concerning the occurence and risk of recurrence of genetic disorders or anomalies within a family. (OB/genetic facts+psychological factors)
- 6. The Burden of Genetic Disorders I. - Rate of aneuploidy in oocytes 18-19% - Rate of aneuploidy in sperms 3-4% - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 1/13 conceptus is chromosomally defective (IVF-PGD) - 50% of 1st trimester spontaneous abortions are due to chromosomal anomalies
- 7. The Burden of Genetic Disorders II. Rate of chromosomal defects 0.65% of all births (clinically significant) Balanced struct. chrom. rearrangement 0.2% of all births Congenital malformations 2 % of all births Perinatal death due to congen defects 30% of all perin.deaths
- 8. The Burden of Genetic Disorders III. Monogenic diseases 3.6/1000 birth Polygenic diseases 46/1000 birth (4.6%)
- 9. Four major questions that have to be answered during genetic counseling What is the disease in question? (clinical and laboratory diagnosis) How severe is it? (prognosis and therapy) How is it inherited? (risk of recurrence) How can it be prevented? (prenat. diagn.)
- 10. What is the disease in question? (clinical and laboratory diagnosis) Medical records Pedigree analysis Special laboratory tests Examination of the relatives Sometimes overlapping phenotypes (similar symptoms, different origin and inheritance eg. „muscular distrophy” (DMD – XR, limb-girdle type - AR, facio-scapulo-humeral muscular distrophy – AD)
- 11. How severe is it? (prognosis and therapy) Medical treatment Surgical treatment In utero treatment (medication or surgery)
- 12. How is it caused/inherited? (risk of recurrence) „high” genetic risk > 10% „intermediate” risk 1-10% „low” genetic risk < 1%
- 13. Different type of risks in Genetic Counseling General population risk (in CF: 1/2500 birth) (every couple has to face this risk) Specific risk (in cystic fibrosis/CF: 25%) (the particular couple has to face for a certain disease with the particular family history) Actual risk (~ 0% or ~ 100%) (calculated for the ongoing pregnancy by the means of prenatal diagnosis)
- 14. How can it be prevented? Prenatal diagnosis
- 15. Definition of Prenatal Diagnosis The main goal of prenatal diagnosis is to provide reassurance to couples at risk that they may selectively have unaffected children even if their procreative risk for having defective offspring is high. („reproductive compensation”)
- 16. Goals of Prenatal Diagnosis To prevent the birth of seriously defective fetuses (to diagnose fetal anomalies – 5%) („secunder prevention”) To make it possible for high-risk couples to have children that they would never have conceived. („reproductive compensation”)
- 17. Results of Prenatal Diagnosis The number of children born because of prenatal diagnosis is much higher, than the number of pregnancies terminated because of the detection of severe fetal defects. („reproductive compensation”)
- 18. Four major questions that have to be answered during genetic counseling What is the disease in question? (clinical and laboratory diagnosis) How severe is it? (prognosis and therapy) How is it inherited? (risk of recurrence) How can it be prevented? (prenat. diagn.)
- 19. Options during Genetic Counseling Option of further pregnancies Option of prenatal diagnosis Option of pregnancy-termination
- 20. Conditions of pregnancy-termination Correct genetic diagnosis (ethics of the investigator and the laboratory) Adequately informed parents (ethics of the genetic counseling) A free decision by the parents (ethics of the couple) Actions taken are within the law (ethics of the society)
- 21. Indications for termination of the pregnancy „Social” indication (up to the 12th week of pregnancy) Medical indications - maternal indication - fetal indication (I. and II.) - maternal-fetal indication
- 22. 1. Maternal indication of termination Termination of the pregnancy may be permitted at any time when serious illness threatens the mother’s life. (heart failure, suicide attempts, etc.)
- 23. 2. Fetal indication of termination I. When the risk of genetic disorder or teratogenic demage to the fetus exceeds 10%, and the disorder/demage is likely to be severe, termination up to the 12th week of pregnancy is permitted.
- 24. 3. Fetal indication of termination II. When the risk of serious genetic disease or malformation in the fetus is between 50% and 100%, and there is no possibility of treatment, termination may be permitted until the 20th week. When a late diagnosis is made because of laboratory delay and not through any negligence on the mother’s part, termination may be permitted up to the 24th week.
- 25. 4. Maternal and fetal indication Occasionally, some severe fetal defects - likely to be fatal in the postnatal period - is discovered after the 20th week. Such pregnancies, if continued, may be accompanied by obstetric complications threatening the mother’s health. (eg. polyhydramnios in case of anencephaly)
- 26. On the other hand… When a disease/anomaly compatible with postnatal life and it is diagnosed after the 20th week, termination is not permitted. The fetus is considered viable, and all efforts should be made to preserve its life and improve its prospects.