9.genetic counselling

complete description of genetic counselling and screening

1. GENETIC COUNSELLING CHAITANYA.P II MDS Dept of Public Health Dentistry

2. Previous questions Genetic counselling (Apr 2010, O ct 2012) Genetics and its applications in dentistry ( A pr 2011) 2

3. contents Introduction Genetic counselling Genetic screening Pedigree charting Prenatal diagnosis Conclusion References 3

4. Genetics The term genetics was introduced by Bateson in 1906.It has been derived from Greek word ‘gene’ which means ‘to become’ or ‘to grow into. 4

5. Brief history Gregor Johann Mendel ( the father of genetics ) 5

6. Genetics Genetics is defined as a branch of medical science which concerned with the transmission of characteristics from parents to offspring. 6 Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn . Oxford: Oxford University Press, 1985.

7. General concept Genetic: Branch of science which studies genes and the pattern of inheritance of particular diseases Inheritance : The passing of familial elements from one generation to the next . 7 Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn . Oxford: Oxford University Press, 1985.

8. 8 Gene – Basic unit of genetic information. Genes determine the inherited characters. It is the functional subunit of DNA and contain instruction for making protein. Chromosomes – storage units of genes. A structure within the cell that deliver the genetic material as DNA.   Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn . Oxford: Oxford University Press, 1985.

9. 9 DNA - is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life Molecule encodes the genetic information. Genome – the collection of genetic information. Carrier individual- individual who appear normal but has one copy of mutant gene. Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn . Oxford: Oxford University Press, 1985.

10. 10 Phenotype: an appearance or characteristic of an individual, which results from the interaction of the person’s genetic makeup and his/her environment. Genotype: the genetic constitution (genome) of a cell, an individual or an organism. Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn . Oxford: Oxford University Press, 1985.

11. 11 Autosomal Dominant: it is one of several ways that a trait or disorder can be passed down through families. ( Or) A gene on one of the non-sex chromosomes that is always expressed, even if only one copy is present . Autosomal recessive: A pattern of inheritance in which both copies of an autosomal gene must be abnormal for a genetic condition or disease to occur Ref: Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn . Oxford: Oxford University Press, 1985.

12. They are of 3 types: 1.Chromosomal abnormalities 2.Mendelian diseases 3.Multifactorial disorders CLASSIFICATION OF GENETIC DISORDERS 12

13. 1.CHROMOSOMAL ABNORMALITIES A. Klinefilter syndrome B. Turners syndrome. 2.MENDELIAN DISEASES A. Dominant B. Recessive C. Sex linked diseases 13

14. 3.MULTIFACTORIAL DISORDERS Hypertension Diabetes Congenital heart disease 14

15. Genetic counselling 15

16. Genetic counselling Genetic counseling is a process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it and the options open to them in management and family planning in order to prevent or avoid it. 16

17. Genetic counselling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates the interpretation of family and medical histories to assess the chance of disease occurrence or recurrence, education about inheritance, testing, management, prevention, resources and research, and counseling to promote informed choices and adaptation to the risk or condition” (NSGC, 2005).National Society of Genetic Counselors 17

18. Aims of genetic counselling The genetic counseling aims to provide the family with complete and accurate information about genetic disorders. Promoting informed decisions by involved family members Clarifying the family’s options available treatment and prognosis Explaining alternatives to reduce the risk of genetic disorders Decreasing the incidence of genetic disorders Reducing the impact of the disorders 18

19. WHO ARE GENETIC COUNSELLERS ? Postgraduates health professionals with a graduate diploma or Master's in genetic counseling. Experience in the areas of medical genetics and counseling. Identify family at risk, investigates the problems present in the family, interpret information about the disorder, analyze inheritance patterns and, risk of re-occurrence & review available option with the family . 19

20. Serves as educators and resource people for other health care professionals and for general public. work in administration capacities. A team of physician, nurse and social worker who undergone special training in genetic counseling Many engage themselves in research activities related to the field of medical  genetics & genetic counseling  20

21. WHAT IS THE ROLE OF GENETIC COUNSELLING ? Genetic Counselors provide genetic information. It is their counselling skills, including their ability to empathically connect with their patients that leads to demands for their skills. Good   Genetic Counselor   have many strengths. They make their clients’ best interest their foremost priority and are keenly attuned to complex professional and ethical challenges. 21

22. Genetic Counselor use non-directive counseling method to provide the best  service to those who need them To develop a mutual relationship with the client, to understand her or him, to relieve any psychological distress, promote a sense of control, and help find  solution to specific problems. 22

23. Assess the client’s strengths, values and needs; provide an individualization and flexible counseling style to suite each client’s need and agenda; develop an awareness of self; and attend to their own inner life. 23

24. The counselor tends to give advice, make decision, be coercive, persuasive, influencing, directing and controlling. The counselor communicates, enables, explores, encourages, informs, offers choices, discusses, promote autonomy, is empathic, non-judgmental, and respectful of the client. 24

25. PRE-REQUISITES OF GENETIC COUNSELLING IS Detailed family history.  Accurate diagnosis. Understanding the medical aspect of the disorder (etiology, natural history, treatment, prognosis, burden ). Understanding the inheritance pattern ( recurrence risk ) Understanding the psycho-social impact of the information. Training / experience in counselling techniques. Understanding the concepts of health / disease / healthcare in the appropriate cultures. 25

26. Function of genetic counselling session Provide information Available solution Help person to understand and cope with his condition Testing the risk of recurrence 26

27. INDICATIONS FOR GENETIC COUNSELLING 1. Hereditary disease in a patient or family 2. Birth defects 3. Mental retardation 4. Advanced maternal age 5. Early onset of cancer in family 6. Miscarriages 7. Malformations 8. Tendency to develop a neurologic conditions 27

28. INFORMATION CONVEYED IN GENETIC COUNSELLING 1. Magnitude of risk of occurrence or recurrence 2. Impact of disease on patient and family 3. Modification of disease impact or risk 4. Anticipated future development 28

29. STEPS OF GENETIC COUNSELLING: Diagnosis Prognosis Treatment 29

30. Genetic counselling ethics Respect the right of individual Non- directive approach Keep privacy of individual and family Maintain the communication between counsellor and his client 30

31. IN SHORT GENETIC COUNSELLING IS Determine the facts : Diagnosis, etiology, and inheritance patterns, prognosis, natural history, treatment and re-occurrence of risk. Transmitting the information : To those requesting it in a sensitive, culturally appropriate, understandable way.  Supporting the decision : Supporting the decision making process of the couple. Genetic counselling : It is non-directive. 31

32. They are of 2 types: 1.Prospective 2.Retrospective GENETIC COUNSELLING 32

33. Prospective genetic counselling This allows for the true prevention of disease . This approach requires Identifying heterozygous individuals for any particular defect by screening Explaining to them the risk of their having affected children if they marry another heterozygote for the same gene. 33

34. If heterozygous marriage can be prevented or reduced, the prospects of giving birth to affected children will diminish. EX: Sickle cell anemia Thalassemia 34

35. 2. Retrospective genetic counselling: Most genetic counselling at present is retrospective, i.e , the hereditary disorder has already occurred within the family . The methods which could be suggested under retrospective genetic counselling are: 1. Contraception 2. Pregnancy termination. 35

36. A survey carried out by the WHO showed that genetic advice was chiefly sought in connection with congenital abnormalities Mental retardation Psychiatric illness Inborn errors of metabolism Premarital advice 36 Ref: Genomics and world health: Report of the advisory committee on health research, Geneva, WHO (2002).

37. The WHO recommends the establishment of genetic counselling centers in sufficient numbers in regions where infectious disease and nutritional disorders have been brought under control And in areas where genetic disorders have always constituted a serious public health problem. 37 Ref: Genomics and world health: Report of the advisory committee on health research, Geneva, WHO (2002).

38. Genetic screening D efinition: A search in apparently normal population for individual with abnormal genes which increase their risk or their offspring of being affected by a disease. 38

39. Types of genetic screening 1. Carrier identification 2. Prenatal diagnosis 3. Newborn screening 4. Forensic screening ( paternity test) 39

40. EARLY DIAGNOSIS AND TREATMENT: 1.DETECTION OF GENETIC CARRIERS : It is possible to identify the healthy carriers of a number of genetic disorders, especially the inborn errors of metabolism. 40

41. 2.PRENATAL DIAGNOSIS: INDICATIONS: - Advanced maternal age - Previous child with chromosome aberration - Intrauterine growth delay - Biochemical disorders - Congenital anomaly - Screening for neural tube defects and trisomy . 41

42. Pattern of inheritance Human cell contain 23 pairs of chromosomes. 22 pairs autosomal and one pair sex chromosomes. 23chromosomes inherited from mother and 23 chromosomes from father. Sex chromosomes: XX for female and XY for male. 42

43. Genetic pedigree: a diagrammatic representation of diseases history in a family up to 3 rd degree relative. 43

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45. Prenatal diagnosis 45 Prenatal diagnosis forms an integral step in genetic counselling. In fact, for couples at risk of a disorder, it is desirable to consider, plan and discuss prenatal diagnosis even before pregnancy. Discussion and planning beforehand will eliminate hurried procedures and emotional trauma as well.

46. 46 Let us now consider the following situations that warrant prenatal diagnosis: It is essential for a genetic disorder in which treatment is either absent or unsatisfactory. Disorder in which an accurate prenatal diagnostic test is possible. Risk to the pregnancy is sufficiently high. The genetic disorder itself is severe enough to warrant termination of preg­nancy. Lastly the termination of pregnancy should be acceptable to the concerned couple.

47. 47 In the following cases, prenatal diagnosis is a must: Maternal age above 35-40 years. If one of the parents is a balanced translocation carrier. In case of an autosomal or X-linked recessive metabolic disorder that is severe but detectable prenatally. Couple already has one child with a neural tube defect

48. Approaches to prenatal diag­nosis 48 Amniocentesis Chorion villous biopsy Ultrasonography Foetoscopy Foetal blood sampling Prenatal Diagnosis Maternal blood screening Preimplantation diagnosis

49. 49 Amniocentesis The ideal time to undertake this investigation is between 14 and 16 weeks when a sufficient amount of amniotic fluid is available for tapping, without harming the conceptus . Procedure: Under ultrasound control, placental localisation is done. Then under local anaesthesia, the fluid is tapped per abdomen avoiding injury to the placenta. A clear tap, not a blood-stained one, must be ensured. About 10-20 cc of fluid is taken out and is subjected to analysis in the laboratory. The cells and fluid are separated by centrifugation. The cells can be studied directly or subjected to culture studies for obtaining foetal karyotype.

50. 50 CHORION VILLOUS BIOPSY In this procedure, chorionic villi are aspirated with the help of canula , which is introduced through the cervix uteri. The procedure is done under ultrasound control. The ideal time to perform chorion villous sampling (CVS) is 8-10 weeks period. However, it may be undertaken till almost 12 weeks .

51. 51 Merits As compared to amniocentesis, CVS claims an advantageous position because it is possible at a much earlier stage of gestation and is easily accepted by patients. Faster result is possible because chorion villi contain enough cells under mitosis so as to permit chromosome analysis without culture. If the results indicate abnormality in CVS, then termination of pregnancy is safer and simpler in first trimester than after amniocentesis (around 18 weeks), which amounts to second trimester abortion

52. 52 ULTRASONOGRAPHY The underlying principle in this procedure is that the echoes generated by the reflection of ultrasound waves are displayed in one of the two ways: B (brightness) Mode: In this, a cross-section of the anatomy is created as transducer is moved across an area. Real Time Imaging: In this, repetitive B-mode images are generated in rapid sequence, allowing appreciation of motion. .

53. 53 Basically, ultrasound serves as an ancillary to amniocentesis. It is helpful in the following ways: Localisation of placenta in amniocentesis or CVS To ascertain gestational age Exclude multiple pregnancy To recognise defects like anencephaly, spina -bifida, micro­ cephaly, hydrocephalous, etc. Limb defects are also evident on ultrasound

54. 54 FOETOSCOPY The procedure involves visualisation of foetus using a fibre optic self-illumi­ nated instrument called foetoscope . It is inserted in the amniotic cavity under local anaesthesia. It is usually done around 18-22 weeks of gestation. With this, one can detect limb malformations, facial defects (cleft lip, cleft palate, ear defects) or defects involving the genitals. The procedure carries a risk of abortion to the tune of 3%-5%. Foetoscopy is useful in obtaining foetoscopic skin biopsy and foetal blood sampling.

55. 55 FOETAL BLOOD SAMPLING (FBS) It can be done in two ways: Placental aspiration (indirect tap) Sampling under direct vision In the former technique, both maternal and foetal blood cells are mixed n eed to be separated before sample processing. In the second case, sample is obtained under direct vision using a foetoscope . Both techniques carry about 10% risk of abortion. There are number of conditions in which FBS is needed to make prenatal diagnosis. They are as follows: Sickle cell disease Thalassaemias Haemophilia A Duchenne muscular dystrophy Immune deficiency disorders

56. MATERNAL SERUM SAMPLE Estimation of AFP(alpha-fetoprotein) in maternal serum is used as a screening test for the detection of neural tube defect. This test is advocated for all pregnant women , realising the fact that about 90% babies with a neural tube defect are born to couples having no family history of such disorder. Maternal serum shows AFP increment during 16-18 weeks of gestation. Elevated AFP in maternal serum is encountered in other conditions, e.g. twin pregnancy and missed or threatened abortion. Having noted elevated AFP, the patient is referred for ultrasonography and subsequently amniocentesis. 56

57. PREIMPLANTATION DIAGNOSIS I t involves egg retrieval from the female followed by in vitro fertilisa­ tion (IVF). The fertilised oocyte is allowed to develop in vitro up to 8 cell stage. A single cell ( blastomere ) from this group is removed, its DNA extracted and amplified by PCR and then analysed to see if there is genetic disorder. If the analysis does not reveal any defect, the conceptus is implanted into the mother's womb. In X-linked recessive traits such as Duchenne muscular dystrophy, the preimplantation diagnosis is used to determine sex of conceptus (since only males are affected). 57

58. 58 Demerits and Limitations Despite PCR even in the best hands, procedure using single cell meets a failure rate of 10%-20%. There is a significant risk of false results because of contamination. Hence, it is safe that an adverse result of preimplantation diagnosis should be followed by invasive prenatal diagnosis using CVS for confirmation.

59. 1.HEALTH PROMOTIONAL MEASURES: A.EUGENICS: a. Negative eugenics: AIM: To reduce the frequency of hereditary disease and disability in the community to as low as possible PREVENTIVE AND SOCIAL MEASURES 59

60. B.POSITIVE EUGENICS: AIM: To improve the genetic composition of the population by encouraging carriers of desirable genotypes. 60

61. B.EUTHENICS : Studies with mentally retarded children indicated that exposure to environmental stimulation improved their IQ. This environmental manipulation is called euthenics. 61

62. OTHER GENETIC PREVENTIVE MEASURES 1.CONSANGUINEOUS MARRIAGES: When blood relatives marry each other there is an increased risk in the offspring of traits controlled by recessive genes and those determined by polygenes. EX: Albinism, Alkaptonuria , Phenylketonuria 62

63. An increased risk of premature death is also noted in such offspring. Therefore, a lowering of consanguineous marriages would be advantageous to the health of the community. 63

64. 2.LATE MARRIAGES: Trisomy or mongolism is more frequent in children born of elderly mothers. Hence early marriage of females is better than late marriage from the point of view of preventing mongolism. 64

65. SPECIFIC PROTECTION: Patients undergoing x-ray examination should be protected against unnecessary exposure of the gonads to radiation. 65

66. Rh haemolytic disease of the newborn which is a genetically determined immunological disorder is now preventable by immunization by anti D globulin. 66

67. Conclusion Many diseases have genetic root The genetic screening is an essential issue in most stages of the life. Genetic counselling aim is to bridge the gap for people between genetic field complexity and their life. 67

68. Reference Jorde Lynn B. Medical Genetics. Mosby, 2005. King RC, Stansfield WD. Dictionary of Genetics. 3rd edn . Oxford: Oxford University Press, 1985 . Harper P. Practical Genetic Counselling. Oxford: Butterworth Heinemann,1993. 68

69. 69 Brock DJH, Rodeck CH, Ferguson Smith MA. Prenatal Diagnosis and Screening. Edinburgh: Churchill Livingstone, 1992. Lilford RJ. Prenatal Diagnosis and Prognosis. London: Butterworth, 1990. K.park’s textbook of preventive and social medicine. 2015, 23 rd edition, bhanot publishers . Genomics and world health: Report of the advisory committee on health research, Geneva, WHO (2002).

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