Genetic counseling in modern dr. sharda jain

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Genetic counseling in modern dr. sharda jain

  1. 1. Genetic Counseling in Modern Obstetrics Dr. Sharda Jain Director :- Sec General : Delhi Gynae Forum
  2. 2. Teacher
  3. 3. DNA Testing Simplified in day- today use (available in INDIA)  Paternity Parentage and relationship testing services  Sibling ship test (Brother /sister)  child swap case  Identification profiling - theft & rape cases  Property dispute Cases  Immigration /Visa purpose  Genetic Test - Anccesity Services
  4. 4. Genetic Predisposing Test  25 chronic disease  7 types caners  Diabetes type 1 & 2  Migraine  Obesity
  5. 5. Background  Genetics: Role in virtual congenital malformation disorders  - Causation - Recurrence Rate - Carrier State - Management Each of us carry at least 20 harmful genes !!! Future counseling will be routine
  6. 6. H/O poly hyd. In 2 preg. Club foot Myotonia
  7. 7. Myopathic facias Myopathic facias
  8. 8. Still birth with talipes + Meningo
  9. 9. Obstetric load  3-4% all births associated with major congenital malformation  1 in 13 conceptus has chromosomal abnormality  50% 1st trimester abortions have chromosomal abnormality  0.2% babies born with balanced chromosomal rearrangements  5.6 & 11.5% still births & neonatal deaths associated with chromosomal defects
  10. 10. No scientific field has greater impact of Genetics on clinical practice than Obstetrics !!!
  11. 11. Basic knowledge of Genetics essential in modern Obstetrics
  12. 12. Some Common Disorders / RR Case Histories Disorder Mode of Inheritance Recurrence risk Method of prenatal diagnosis ß – thalassemia Autosomal recessive 25% Mutation detection Sickle cell disease Autosomal recessive 25% Direct detection of mutation Spinal muscular Atrophy Autosomal recessive 25% Mutation detection Cystic Fibrosis Autosomal Recessive 25% Mutation detection
  13. 13. Disorder Mode of Inheritance Recurrence risk Method of prenatal diagnosis Duchenne Muscular Dystrophy X- linked recessive 25% of all children or 50% of male children Mutation detection Achondroplasia Autosomal dominant 50% if one parent affected Mutation detection Neural Tube defect Unknown 3-5% after one 10% after two Ultrasound / a FP
  14. 14. Objectives of good counseling Need of GC extended to all pregnant women  Help family comprehend medical facts about disease  Emphasize role of heredity in occurrence & risk of recurrence  Elaborate options for dealing with RR  Help choose appropriate course of action in view of family goals  Help family members to accept disorder or its RR  PGD
  15. 15. Indications of GC in Obstetrics  Advanced maternal age  Abnormal maternal serum screening test result  Abnormal USG evaluation during pregnancy (fetus/ amniotic fluid)  Previous fetus / child with genetic disorder / CMF/ MR  Family history of genetic disorder  Maternal disorders associated with increased risk of fetal CMF or exposure to teratogens  Consanguinity  Bad obstetric history (RSA, Unexplained IUD or still birth & NND)
  16. 16. Common areas for Genetic Counseling in obstetric practice
  17. 17. Pre-conception counseling  Ideal time for GC in Obstetrics  Opportunity to screen & discuss conditions that can affect pregnancy outcome
  18. 18. Screening for Common genetic disorders in community  USA: Tay Sachs ds, Sickle cell anm & Thalassemia  India: Thalassemia  Couples counseled about reproductive alternatives - prenatal diagnosis - artificial insemination - deferral of childbearing 1st Problem 3 case studies
  19. 19. Carrier state can be diagnosed in Delhi  Thalassemia  Sickle cell dis  Cystic Fibroids  Spinal Muscular Atrophy (SMA)  Duchene muscular dystrophy  Haemophilia  Achondroplasia
  20. 20. Advanced parental age  Maternal age: increased risk of chromosomal abnormality (Trisomy 13, 18, 21, 47XXY, 47XXX)  Paternal age: increased risk of Autosomal dominant, X- linked recessive Ds 2nd Problem
  21. 21. Screening for Major Fetal malformation  All pregnant women: 3-4% risk of CMF in fetus  Routine screening by USG at 16-18 weeks: Detection rate 50-75%  Sensitivity 53-75% in low risk women  Component of routine antenatal care 3rd Problem
  22. 22. Soft markers for Fetal aneuploidy 4th Problem NT NB Echogenic Bowel Echogenic heart focus Short humerus Short femur Choroid Plxus Cyst Pyelectasis
  23. 23. 4th Problem Down syndrome Patau Syndrome Edward Syndrome
  24. 24. Screening for Chromosomal aneuploidy  Each pregnancy: 0.6% risk;  Commonest Trisomy 21  Dual test / Triple test offered to all pregnant women  Risk of trisomy calculated by computer program  Screen +ve (risk above specified cut-off): Offered prenatal diagnosis  Detection rate: 75-89% 5th Problem
  25. 25. “FASTER” TRIAL NEJM 2005 First- and Second-Trimester Evaluation of Risk Research Consortium trial  First trimester - 85 - 87 % detection rate  Quadruple test – 81 % detection rate  Triple test – 69% detection rate  Sequential test – 95 -96 % DR Earlier is clearly better
  26. 26. Policy to sort out which baby affected  Fish test  Culture for karyotyping < 1 : 50 > 1: 1500 50 : 1500
  27. 27. What laboratory test Q1.Only FISH ? FISH and culture ? case study --------------------------------------------------------------- Q2.---Does a chromosomal analysis suffice for all genetic disorders ?  Molecular analysis for single gene disorders  Enzyme testing for biochemical disorders  Amniotic fluid analyte testing like CAH, urea cycle disorders
  28. 28. Case History Positive triple test AFP – 0.59 MoM uE3 – 1.10 MoM HGG –3.57 MoM Triple risk for DS – 1 :130 USG at 15 wks: NFT – 1.2mm, DV flow - normal 27 yrs 17 weeks gestation FISH analysis - normal
  29. 29.  Unbalanced chromosomes in the fetus  Not compatible with normal phenotype  46,XX,der(5)t(5;8) (p13;q22)  Missed if karyotype not performed Culture remains GOLD Standard FISH + culture performed together
  30. 30. Non – Invasive prenatal genetic testing for fetal Down Syndrome- the NIFTY test
  31. 31. Comparison of prenatal screening any diagnosis tests for fetal Down Syndrome Method Detection Rate Missed Diagnosis False Positive Rates Limitations Amniocentesis 100% 0% 0% 0.5% abortion risk Done after 19 weeks Chorionicc Villus sampling (CVS) 100% 0% 0% 0.5% abortion risk Done in 11-13 week First Trimester Combined screening (OSCCAR) 90% 10% 5-7% Must be done in 11-13 week Mid- Trimester maternal serum 65% 35% 5-7% Must be done in 14-20 week NIFTY >99% <1% <1% Can be done any time after 12 week
  32. 32. Previous child with Down’s syndrome  F/H +ve: Increased risk upto 3rd degree relative  R/R depends on Karyotype of affected child - Trisomy: R/R 1% above maternal age specific risk - Translocation: Mother carrier- 15% (100% if t 21;21) Father carrier - 5% De novo - 2-3%  Amniocentesis offered to all at 16-18 weeks 5th (B) Problem
  33. 33. Previous child with aneuploidy  R/R usually < 1%  Karyotyping of parents only if structural abnormality of chromosomes like translocation or duplication or deletion in child  Exact counseling depending on type of abnormality detected  Prenatal diagnosis available  Extended family counseling if a parent found to be a carrier of a balanced structural rearrangement 5th (A) Problem
  34. 34. Previous child with NTD  Commonest congenital malformation (1/1000 live births), incidence higher in North India  R/R: - 3-5% after 1 affected child - 10% after 2 affected children - 25% after 3 affected children  Correct diagnosis important for proper counseling (R/o monogenic syndromes, chromosomal ds & environmental factors)  MSAFP & USG at 16-18 weeks for diagnosis 5th (c) Problem
  35. 35. Previous child with mental retardation  Prevalence of MR in general population: 2-3%  R/R varies from 0-50% depending on cause of MR (identified in 40-60% cases)  Associated malformations suggest a genetic etiology  No cause known: give empiric figures (5-7%)  R/R modified according to associated features  Both parents normal, one has affected sibling: 2.5%  Both parents normal but one affected child: 12.5% 5th (D) Problem
  36. 36. Recurrent abortions  Incidence: 0.8% -1% couples  Recombinations & abnormal segregation produce gametes with partial trisomy / monosomy  Karyotype of couple advised after ruling out non-genetic cause  Risk of RSA in translocation carriers: 20-30%  Risk of RSA in carriers of pericentric inversion: 40-50%  Risk more if previous baby with CMF & chromosomal abnormality  Risk more if mother is a carrier 7th Problem
  37. 37. Counseling in carriers of chromosomal rearrangements  Explain risk of abortion, liveborn with chromosomal imbalance & normal liveborn  Need for CVS / amniocentesis  USG for fetal malformations  Siblings of carriers offered karyotyping before pregnancy
  38. 38. Karyotyping products of conception How important it is ?? (Chrosomes 13,18,21,X& y)  Only indicated in RSA, may give idea of possible chromosomal rearrangement in parents  Karotyping in couple more informative  Absence of structural chromosomal abnormality does not rule out possibility of chromosomal rearrangement in parents
  39. 39. Still birth  Incidence of chromosomal abnormality 10 times (5.6%) compared to live births (0.6%)  Fetal autopsy ,chromosomal analysis, radiography & clinical photography must be done in all  Important for providing more definitive cause of loss and R/R for future pregnancy 8th Problem
  40. 40. Polyhydramnios & oligohydramnios  Polyhydramnios associated with structural abnormality in 10-20% cases  Incidence of chromosomal abnormality: 3.2%  Karyotype recommended if polyhydramnios associated with structural abnormality  Oligohydramnios associated with aneuploidy & fetal malformations (renal agenesis, renal dysplasia, post uretheral valve) 9th A. Specific Condition
  41. 41. Early onset IUGR  High risk pregnancy: 5% SGA have chromosomal abnormality  Indication for chromosomal studies  25-35% fetus with chromosomal abnormality have no structural anomaly on USG except IUGR 9th B. Specific Condition
  42. 42. USG detected malformation  Targeted scan for associated malformations, Fetal ECHO, Fetal karyotyping essential  Prognosis depends on type & severity of abnormality, associated malformation & chromosomal abnormality (1/3rd cases)  Dilemma about continuation of pregnancy: Careful counseling about diagnosis, prognosis & future implications  Fetal autopsy after termination 10th Problem
  43. 43. Prenatal diagnosis  Choice should be personal based on non-directive counseling  Couple informed about all options  Counsel about risk associated with PND procedures  Discuss limitations & implications of test results  Discuss reproductive options before offering tests  PND only after written informed consent  Precise mutation/ defect should be demonstrated in proband before attempting PND
  44. 44. Take home message… Gynaecologist have to know basics in GC  All pregnancy need GC  Increased public knowledge & expectations with introduction of triple marker screening, TIFFA & access to prenatal diagnosis  Failure to prevent birth of abnormal baby: Medico-legal consequences  Future of genetics in obstetrics: Genetic testing will become commonplace & will replace current diagnostic tests  GC in Infertility Male & Female
  45. 45. Torch Infection Through Case Studies Harmonse Drugs X-Ray/CT/MRI Other Viral Infection eg Chicken Pox Case Study Specific Medical disorder Safety / Risk Eg HIV,TB, epilepsy
  46. 46. Thank You

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