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Indications for genetic research in Obstetrics and Gynecology 1. Prenatal diagnosis

Indications for genetic research in Obstetrics and Gynecology 1. Prenatal diagnosis 2. Reproductive failures (both parents) - miscarriage (2 and more) - stillbirths - children with birth defects 3. Disorders of sex determination 4. Hereditary cancers. Prenatal diagnosis.

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Indications for genetic research in Obstetrics and Gynecology 1. Prenatal diagnosis

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  1. Indications for genetic research in Obstetrics and Gynecology 1. Prenatal diagnosis 2. Reproductive failures (both parents) - miscarriage (2 and more) - stillbirths - children with birth defects 3. Disorders of sex determination 4. Hereditary cancers

  2. Prenatal diagnosis

  3. The etiology of congenital malformations

  4. Prenatal diagnosis defonition Diagnosis before birth. Methods for prenatal diagnosis include ultrasound of the uterus, placenta, and/or developing fetus; chorionic villus sampling (CVS) to obtain tissue for chromosome or biochemical analysis; and amniocentesis to obtain amniotic fluid for the analysis of chromosomes, enzymes, or DNA. A growing number of birth defects and diseases can be diagnosed prenatally and in some cases treated before birth. Also known as antenatal diagnosis.

  5. Congenital anomalies 3-4% of newborns 0,4– 0,6% - newborn affected by a chromosomal aberrations (reprodactive failure and stillbirths) More than 10 000 monogenic diseases 10% - causes of hospitalization – monogenic diseases 7% stillbirthsm and perinatal deaths) - mitochondrial myopathies conditional mutations in mitochondrial or nuclea DNA 20% - poligenic diseases

  6. Malformations and genetic diseases cause a higher incidence causes: - hospitalization, - morbidity, - mortality, Social and economic problemMost genetic diseases manifested by symptoms: - physical disability - intellectual disability

  7. 1. The correct diagnosis of the disease, 2. Construction and analysis of pedigree: - family members who incur greater risk, - how extensive diagnostic tests should be foreseen and planned. 3. Assessment of genetic risk.

  8. Principles of genetic counseling 1. Genetic advice should be granted when the family is interested in its acquisition 2. It must be informative, non prescriptive ! The content of advice has a significant impact on the decision to abandon the planning or subsequent pregnancies, and sometimes determine the continued operation of the famil WHO defined ethical principles that should apply in genetic counseling.

  9. Principles of genetic counseling Decisions, regarding both planning to become pregnant, as well as acceptance of prenatal diagnosis, termination of pregnancy after the detection of fetal disease or adoption should be made by the same consulted in accordance with their knowledge, beliefs, recognized worldview, life goals and values system.

  10. Down syndrome- classical trisomy 95 % - chromosomal translocations 4% * de novo*carriers of balanced translocation of chromosome 21 to another acrocentrical chromosome - mosaicism 1-3%

  11. Downa syndrome Patau syndrome 1:680 1:5000 - 47, XY,+21 47,XY,+13

  12. Frequency of population is1:680

  13. Genetic risk of aneuploidy 1. The risk of many aberrations (tris. 21, 13, 18) - increases with maternal age. No risk for sex chromosome aberrations (X i Y) - decreases with advancing pregnancy (greater risk of fetal death)

  14. The risk of trisomy 21 in each age group.

  15. The risk for trisomy 21: Increases with maternal age Decreases with gestational age because about 30% of affected fetuses die between the 12th and 40th week of pregnancy

  16. Maternal age The risk for trisomy 21 increases with maternal age but because there are a lot more women in the younger age group the majority of fetuses with trisomy 21 are in the women aged under 35 years In the 1970’s and 1980’s screening for trisomy 21 was based on maternal age and amniocentesis or CVS was offered to those aged 35 years or older.

  17. About 5% of pregnant women were ≥35 years and a policy of screening based on maternal age would result in: Invasive testing rate 5% Detection rate of trisomy 21 30% In most developed countries in the last 30 years the maternal age of pregnant women has increased and now about 20% of pregnancies, including 50% of fetuses with trisomy 21, are in women aged ≥35 years

  18. Determination of recurrence risk of aneuploidyi Pregnancy with trisomy - the risk increased by 0.75 per cent. than the risks arising from the patient's age

  19. The causes of aneuploidy repeat - < 35 r.ż. - the tendency to non - disjunction- gonadal mosaic - chapter gene defect- >35 r.ż. accumulation of errors(free radicals, hormonal disorders) The risk for relatives of second and third degree - no more than population

  20. Mejotic division Parents Meiosis Mejosis normal gamete

  21. failed separation of chromosomes during meiosis Parents Meiosis I Meiosis II normal gamete fertilization offsprong

  22. 46,XY,+t(14;21)(q10;q10)+21 46,XY,+t(21;21)(q10;q10)+21

  23. The distribution of risk in the event of a merger centric carrier 14; 21 eg. in the mother 14;21 Healthy child The egg in the mother can randomly hit chromosomes indicated its karyotype It was assumed that sperm is always correct the chromosomal Healthy carrier

  24. The distribution of risk in the event of a merger centric carrier 14; 21 in the mother. Trisomy 14 - lethal Trisomy 21; Downa syndrome

  25. The distribution of risk in the event of a merger centric carrier 21; 21 eg. in the mother mother with a pair of chromosomes 21, but connected to each othe No chromosomal 21 materna Trisomiy 21; ZD Monosomy 21; lethal 100% risk score for each child born ZD

  26. the risk of repetition t(14;21)(q10;q10) Mother 10- 15 % Father 5 – 10 % t(21;21)(q10;q10) Mother 100 % Father 100 %

  27. 46,XY,+t(14;21)(q10;q10)+21 VSD VSD VSD 3 2 VSD

  28. Comprehensive prenatal diagnosis: Non-invasive prenatal diagnosis 1. Ultrasound of 11, 20, 30 weeks of pregnancy. 11 -13.6 hbd (45 - 84 mm) - Nuchal scan, NB, TV, DV.- first trimester test (double test (PAPP A + beta hCG) (11 -13.6 hbd) (sensitivity 70%) - second trimester test (triple test (beta hCG, AFP, estriol) (sensitivity 60%) NT + T I + T II sensitivity = 85 – 90 % ! False positive results - 5 % Invasive prenatal diagnosis ! - chorionic villus sampling >12Hbd- amniocentesis > 15 HBD - cordocentesis >18 Hbd

  29. Nuchal translucency (NT) is the sonographic appearance of a collection of fluid under the skin behind the fetal neck in the first trimester of pregnancy

  30. 47,XY,+21

  31. 47,XY,+21

  32. 46,XY,+13 Patau Syndrome 45,XX,+t(13;14)(q10;q10)‏

  33. 47,XY,+13

  34. 47,XY,+13

  35. 47,XY,+13

  36. The increased translucency can be present in: - syndromes associated with chromosome aberrations: z. Syndrome, z. Edwards - syndromes with normal karyotype: with. Noonan, SLOS - heart defects coexisting with defects in other organs - 1/3 of the lack of reasons - healthy children NT>95 percentile - assess the fetal karyotype percentile

  37. Attention ! Each invasive procedure should be preceded by an exhaustive conversation with the patient, during which detailing all of the risks that the mother and the child brings with it the treatment. Each invasive procedure requires the written consent of a patient's own signature confirms that it agrees to perform the surgery and that was exhausting informed about the surgery and its complications and risks associated with him.

  38. Amniocentesis

  39. Diagnosis of fetal chromosomal abnormalities requires invasive testing by amniocentesis or chorionic villous sampling (CVS)

  40. 3D USG

  41. 3D USG

  42. Risks associated with amniocentesis or CVC 0,5 –1,0 % - Bleeding - Amniotic infection syndrome - Maternal - Fetal transfusion - Premature rupture of the bladder - Fetal / PROM / - Hematoma or placental - Release of uterine contraction

  43. Risks associated with invasive procedures Ultrasonography - unknown CVS < 12 tyg. - limb defects may occur (thrombotic lesions) CVS > 12 tyg. - 0,5 -1,0% Amniocentesis 13-14 tyg. - 3% Amniocentesis 15-17 tyg. - 0,5 – 1,0% Cordocentesis > 17 tyg. - 2,0 % Doppler waves - have a higher frequency and greater thermal effec

  44. Risk of Amniocentesis Amniocentesis should not be performed before 16 weeks because with early amniocentesis the rate of miscarriage is about 2% higher and the incidence of talipes equinovarus is 1.5% higher than after first-trimester CVS or second-trimester amniocentesis !.

  45. Risk of CVS CVS should not be performed before 11 weeks because earlier CVS is associated with fetal transverse limb abnormalities, micrognathia and microglossia

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