1. Furdela Victoria MD. Assistant Pediatrics Department #2

2.  What is the genetic counseling?  Genetic counseling may be described as the process through which individuals affected by, or at risk for a problem which may be genetic or hereditary, are informed of :  The consequences of the disorder,  The probability of suffering from or of transmitting it to their offspring,  The potential means of treating or of avoiding the occurrence of the malformation or disease

3. The structure of Medical genetic counseling includes:  Geneticist  Gynecologist  Endocrinologist  Neurologist  Psychologist  Genetic laboratory 

4. WHO ARE GENETIC COUNSELLERS ?  They are postgraduates health professionals with a graduate diploma or Master’s in genetic counseling.  They have an experience in the areas of medical genetics and counseling.  They 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.  They serves as educators and resource people for other health care professionals and for general public.  Many engage themselves in research activities related to the field of medical genetics & genetic counseling

5.  Genetic Counselors provide genetic information. It is their counseling 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.  Genetic Counselor use non-directive counseling method to provide the best service to those who need them.  If directive counseling are used, the counselor tends to give advice, make decision, be persuasive, influencing, directing and controlling.  If non-directive counseling methods are employed the counselor communicates, enables, explores, encourages, informs, offers choices, discusses, promotes autonomy,is empathic, non-judgmental, and respectful of the client.  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.  They need to be able to : 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

6.  Child with a birth defect, or suspected birth defect  Child with a suspected or diagnosed genetic syndrome  Child with a chromosomal syndrome  Child with a metabolic disorder  Child with developmental delays  Child with a family history of a genetic condition

7.  Adult with a genetic condition who would like periodic monitoring by a specialist  Adult with a family history of a genetic condition  Adult with a strong family history of common adult onset disorders such as heart disease, senility, or diabetes  Adult with a strong family history of cancer  childless marriage

8. Those who can benefit from genetic counseling include those who have a history of: ♦ A known genetic disorders e.g. Cystic Fibrosis, Hemophilia, Down’s syndrome ♦ Birth defects eg. Spina Bifida, Cleft Lip and Palate, Congenital heart disease, club foot ♦ Inherited Cancers e.g. Breast and Bowel Cancers ♦ Intellectual disability ♦ Hearing or visual disability ♦ Infertility or multiple miscarriages or infant deaths ♦ Genetic defects occurring frequently in special ethnic and rational groups e.g. Tay-Sac disease, Sickle cell Anemia, Thalassemia.

9.  What is the nature of the disease (congenital, inherited or acquired)?  How to treat the disease?  How does it can end?  Can this appear in other children in the family?

10.  Establishing the correct diagnosis  Establishing the heredity family type  Calculation of the risk for next children with heredity diseases  Explanation to parents about risk of heredity diseases for next children and maximum support in there decision

11.  1) Collecting anamnesis  2)Arriving at a specific diagnosis : *Advantages: Cornerstone for genetic counseling. *Disadvantages:  Most difficult, trying and time consuming part of the process, for the health care professionals as well as for the family.

12.  3)Estimation of risks: to develop the disorder and/or to transmit it to offspring.  4)Informing the family  5)Psychological assessment and counseling.  6)Practical aid: this includes recommending:  Doctors for specialized examinations  Health care professionals for speech or educational therapy.  Coordination of prenatal and other diagnostic tests.

13.  7) making decision  8)Supportive role: Accepting and learning to live with a genetic diagnosis is particularly difficult when reproductive options are involved, and feelings of " guilt " may touch several generations.

14.  Genetic anamnesis (presents of inherited family diseases, infant death, abortions, fetus death, long barrenness)  Dysmorphic signs  Low birth weight  High morbidity and mortality  Mental retardation  Ocular and ear defects  Skeleton abnormalities  Abnormalities of internal organs

15.  Detailed family history  Drawing the pedigree for the family  Assessment of patients phenotype  Understanding the inheritance - pattern recurrence risk  Using of additional method of examination  Accurate diagnosis  Understanding the psycho-social impact of the information  Making decision 

16.  The steps {to be taken, depending on whether the specific diagnosis is established or not}, can be summarized as follows:  (1)Obtaining a detailed family history, which includes both sides of the family even if counseling has been requested for a dominant disorder affecting one parent.

17.  (2)A review of medical and/ or pregnancy histories is especially important when the diagnosis is not yet established, but also helps geneticists to learn more about etiologies and natural histories of certain disorders.  (3)A physical examination, of the affected person, and sometimes of other family members, is often needed.

18.  (4)Medical and/or laboratory exams :  These often include chromosome study, and may necessitate DNA analysis if the identity of the gene suspected to be involved is known.  Other frequent suggestions include X-ray or ultrasound examinations, and various biochemical analyses.  Once the diagnosis is known, medical tests aimed at evaluating health risks linked to the disorder may also be established.

19. History of congenital abnormalities Neural tube defects Neural tube defects Heart defects Heart defects Cleft lip or palate Cleft lip or palate Other Other Chromosomal abnormalities Down syndrome Down syndrome Mental retardation (e.g., fragile X risk) Mental retardation (e.g., fragile X risk) Other Other

20. Maternal age >34 or advanced paternal age Inherited diseases Hemoglobinopathy Hemoglobinopathy Muscular dystrophy Muscular dystrophy Cystic fibrosis Cystic fibrosis Huntington's chorea Huntington's chorea Hemophilia Hemophilia Metabolic disorders (e.g., phenylketonuria, diabetes) Metabolic disorders (e.g., phenylketonuria, diabetes) Kidney disease Kidney disease Other Other

21. Ethnicity European (phenylketonuria risk) European (phenylketonuria risk) Eastern European Jews (Tay-Sachs, Canavan risk) Eastern European Jews (Tay-Sachs, Canavan risk) French Canadians (Tay-Sachs risk) French Canadians (Tay-Sachs risk) Mediterranean (Hemoglobinopathy risk) Mediterranean (Hemoglobinopathy risk) Asians (Hemoglobinopathy risk) Asians (Hemoglobinopathy risk) African (Hemoglobinopathy risk, sickle cell anemia) African (Hemoglobinopathy risk, sickle cell anemia) Hispanic (Hemoglobinopathy risk) Hispanic (Hemoglobinopathy risk) Other Other Consanguinity Recurrent pregnancy loss or stillbirth Maternal metabolic disorder

22.  It is important to draw the pedigree or family. This method helps to show the number of involved family members, their sexes and ages of onset etc.  to determine the type of inheritance and further chances of recurrence of the inherited disorder.

23. Healthy woman Healthy man Healthy manProband Sex unknown Dead

24. Abortion Medical abortion Still-birthMarriage Consanguineous marriage Repeated marriage UnmarriageSiblings

25. Monozygotic twins Dizygotic twins No known pregnancy Sterility

26. Known heterozygous person Carrier female Pregnancy in progress Affected person

30. Assessment of patients phenotype

31. Mongoloid eyesAntimongoloid eyes

41.  (1)Chromosomal disorders:  Incidence: 1/200 live-born children, and 1/500 adults.  Abnormalities :  1) Numerical abnormalities : rarely inherited, although the extra chromosome is transmit to the offspring.  2)Structural abnormalities, such as translocations, May cause: little or no effect in carriers, but predispose to reproductive problems such as miscarriage and infertility.

42.  CAUSE: Mutations in single genes, at specific gene " loci.  Incidence: 1/300 individuals will suffer from a monogenic disease manifesting within the first two decades.

43.  Four types of transmission :  a) Autosomal dominant: (One mutated gene of the pair is sufficient to produce symptoms),  b) Autosomal recessive :(The two alleles must be abnormal to cause the phenotype)  c) X-linked, which includes:  1) X-linked, recessive (Theoretically, only males suffer, given that they are " hemizygous " for the X chromosome) and, less frequently.  2)X-linked dominant gene mutations (Males more seriously affected than females).

44.  Polygenic implies that the association of several different genes, each one slightly modified, is necessary to produce the disorder.  Multifactorial causation means that both genetic and non-genetic (environmental, either pre- or postnatal) factors are associated to produce the pathology.  5-10% of the population will suffer either from a malformation or from a disease in which genetic factors are major.

45.  In recent years a " new " type of inheritance has been proven, that resulting from mutations in the mitochondrial genome.  The incidence: of mitochondrial mutations in human disease is still unknown.  In many cases the mutation is " de novo " in an affected individual, but hereditary transmission is purely maternal, since, a fertilized egg’s mitochondria originate from the maternal germ cell only.

46.  1)Chromosome studies.  2)DNA studies.  3)Biochemical genetic studies.

47.  "Cytogenetics" is a word used to describe the study of chromosomes.  The chromosomes need to be stained in order to see them with a microscope.  When stained, the chromosomes look like strings with light and dark "bands.  " A picture (an actual photograph from one cell) of all 46 chromosomes, in their pairs, is called a "karyotype."

48. Cytogenetic method This method give us possibility to examine establish This method give us possibility to examine X and У sex chromatin and autosomes to establish karyotype.

49.  The standard analysis of the chromosomal material evaluates; both number and structure of the chromosomes, with an accuracy of over 99.9 percent.  Chromosome analyses are usually performed using :  Blood sample (white blood cells),  Prenatal specimen,  Skin biopsy, or  Other tissue sample

51. Abnormality Incidence (% of total) Trisomy 13 2 16 15 18 3 21 5 other 25 Monsomy X 20 Tripoloidy 15 Tetraploidy 5 Other 10

52. Abnormality Incidence per 10,000 births Autosomal trisomy 13 2 18 3 21 15 Sex Chromosomes Female births 45, X 1 47,XXX 10 Male births 47, XXY 10 42, XYY 10

53. Cytogenetic testing - Down syndrome normalabnormal

54. Cytogenetic testing - Deletions

58.  (A) indirect DNA studies  Involve using "markers" to find out whether a person has inherited the crucial region of the genetic code that is passing through the family with the disease.  Markers are DNA sequences located close to or even within the gene of interest and almost always inherited together.  Because the markers are so close, to a gene, they are said to be "linked."  The accuracy of linkage studies depends on how close the markers are to the faulty gene.

59.  (B) Direct DNA studies:  Look directly at the gene in question for an error.  Errors in the DNA may include :  Replication of the gene's DNA (duplication),  Loss of a piece of the gene's DNA (deletion),  Alteration in a single unit (called a base pair) of the gene's DNA (point mutation),  Repeated replication of a small sequence of the gene's DNA.

61.  When a particular mutation is found in a relative with cancer, other family members should be tested for the mutation to determine the risk to develop cancers and to pass the mutation on to the next generation.  The DNA needed for direct DNA studies is usually obtained by taking a blood sample.

63.  Biochemical genetic testing involves:  ( A) The study of enzymes in the body that may be abnormal in some way.  Sometimes, it is easier to study the enzyme itself (the gene product).  Biochemical genetic studies may be done from;  a blood sample,  urine sample, spinal fluid, or  other tissue sample, depending on the disorder.

64.  Sometimes a mutation in a gene causes it to make a protein that is truncated (shortened).  Protein truncation studies can be performed on a blood sample.  These types of studies are often performed for disorders in which the known mutations predominantly lead to shortened proteins.

65.  Both parents should be included in genetic counseling  Enough time should be given for counseling  The counselor should be flexible and should not impose decision on the family

66.  Avoid of marriage with relatives  Abandon child birth  Adoption of orphan  Artificial impregnation  Provide Prenatal Genetic tests  Indicate for artificial abortion

67.  Gene engineering  Forbidding of marriage with relatives  Mixing of population  Establishing of recessive genes and their treatment

68. The term prenatal diagnosis describes various procedures (invasive and non-invasive methods) of prenatal diagnosis. The procedures serve to detect high-risk pregnancies, high-risk childbirths and disturbances of health at an early stage and thus to avert in time dangers for life and health of mother and child

69. Advancing capabilities in the detection of genetic abnormalities and monitoring fetal development have enabled the prenatal diagnosis of a wide variety of congenital and acquired conditions. It is now possible to determine whether a fetus is affected with a specific genetic or acquired disorder rather than relying on probability assessment and statistical analyses to assess fetal risk.

70.  Indirect  Direct  Invasive  Non-invasive

71.  Clinical examination  Obstetric gynecologic examination  Microbiological examination

72.  Analysis of specific embryonic albumens (alpha-fetoprotein, chorionic gonadotropin, estriol)  Analysis and DNA-analysis of embryonic erythroblast from blood of pregnant

73. Non-invasive methods of PND are such prenatal examinations that do not invade into the body of mother or child. This includes various forms of sonography (acoustic discharge measurement) and electrocardiography. The side-effects of non- invasive methods for mother and child are assumed to be minimal.

75.  Amniocentesis  Chorionic villus sampling  Fetal blood sampling  Fetal skin sampling  Fetoscopy

76.  1 Combined test + Ultrasound (the first 10 weeks)  2 Triple test, ultrasound, amniocentesis, cord centesis (16-20 weeks)  3 Ultrasound and Dopler ultrasound (32-36 weeks)

77.  1-Maternal age ≥ 35 yrs at delivery  2-Mother's serum screening test indicates an increased risk for :  Neural tube defects, Down syndrome, or trisomy 18  3-Abnormal prenatal test results or abnormal prenatal ultrasound examination.

78.  4-Previous child with or family history of birth defects and /or mental retardation.  5-Either parent :  Carries a balanced chromosome abnormality.  Affected with autosomal dominant disorder such as myotonic dystrophy.  6-Both parents: Carriers for an autosomal recessive disorder (e.g. Cystic fibrosis and sickle cell anemia,)  7-Mother : Carrier of an X-linked recessive disorder (i.e. hemophilia, Duchene muscular dystrophy).

79.  8-Previous unexplained stillbirth or two or more previous spontaneous abortions.  9-Preconceptional couples with high risk factors such as advanced age, incest or a close blood relationship.  10-Family history of :cancer, particularly at younger ages  11-Exposure to teratogens: Toxic or carcinogenic agents such as drugs, chemicals, radiation or infections during critical periods of fetal development

80.  12-Extreme parental concern or fear of having a child with a birth defect  13-Infertility cases where either parent is suspected of having a chromosomal abnormality  14-Mother's illness, in which fetal abnormalities may be associated with the disease or with medications prescribed for the condition

81.  Used to identify or confirm the diagnosis of a disease or condition in a person or a family. It gives a "yes" or "no" answer in most cases.  Determining the course of a disease and the choice of treatment.  Examples :include chromosome studies, direct DNA studies, and biochemical genetic testing.

82.  Determines the chances that a healthy individual with or without a family history of a certain disease might develop that disease.

83.  Used to determine whether persons who have a family history of a disease, but no current symptoms, have the gene alterations associated with the disease or not.

84.  Determine whether a person carries one copy of an altered gene for a particular disease

85.  Used :to diagnose a genetic disease or condition in the developing fetus.  It includes :  Maternal serum screening,  Ultrasound (sonograms),  Amniocentesis,  Chorionic villus sampling (CVS), and  Percutaneous umbilical blood sampling (PUBS).

86.  Used following IVF to diagnose a genetic disease or condition in an embryo before it is implanted into the mother's uterus.  (7)Newborn screening  Performed in newborns in state public health programs to detect certain genetic diseases for which early diagnosis and treatment are available.

87. Regardless of the specific indication, invasive prenatal testing should be performed with detailed genetic counseling performed before the procedure. Such counseling is needed to obtain critical information from the patient to assess properly fetal risk; to review personal and family histories that have an impact on this risk; to describe the risks, benefits, and limitations of the procedure(s) to be offered; and provide empathetic support to women who are considering such testing. Genetic counseling should be provided in a nondirective fashion, thus providing women with the necessary information (written and verbal) to arrive at prenatal diagnostic decisions but without coercing the woman, either overtly or covertly, into making a particular decision.

88. Amniocentesis, the aspiration of amniotic fluid, has traditionally been performed at and after 15 to 17 weeks of gestation. At this stage of gestation, the volume of amniotic fluid is about 200 mL. The ratio of viable to nonviable cells in the amniotic fluid is relatively high, thus allowing timely culture and diagnosis of fetal cytogenetic abnormalities and providing women the option of pregnancy termination should an abnormality be determined.

89.  It is very important method of prenatal diagnose which give the possibility to estimate sex of fetus, some hereditary diseases and after genetic counseling to decide the question about abortion

90.  Because amniocentesis is most commonly performed in the midsecond trimester (15 to 16 weeks), fetal diagnosis cannot usually be established before 17 to 18 weeks of gestation. A technique that could be performed during the first trimester would be highly desirable to reduce the psychological stress of awaiting results until midpregnancy and to allow a safer method of pregnancy termination, should an abnormality be detected. CVS is such a technique.

91. Transcervical CVS is now usually performed at 10 to 12 completed gestational weeks. Absolute contraindications to transcervical CVS include active cervical or vaginal pathology (e.g., herpetic, chlamydial, or gonorrheal infection) or maternal blood group sensitization. Relative contraindications include leiomyoma obstructing the cervical canal, bleeding from the vagina within 2 weeks of planned CVS, and a markedly retroverted, retroflexed uterus.46 Before CVS, fetal viability and normal fetal growth must be confirmed by ultrasound. The procedure is performed with a device that consists of a plastic cannula enclosing a metal obturator extending just beyond the catheter tip; the diameter of most catheters is approximately 1.5 mm.

92.  Transabdominal CVS applicable to evaluate pregnancies at the same gestational age as transcervical CVS at 10 to 12 weeks; however, this procedure also can be performed later in pregnancy, particularly when fetal abnormalities are visualized at ultrasound and a rapid diagnosis may influence pregnancy management. Placentas especially amenable to the transabdominal approach include those located in the fundus or those located anteriorly in an anteflexed uterus. Transabdominal CVS is also an option in certain circumstances when transcervical sampling is contraindicated (e.g., active herpes or cervical lesions).

94.  Access to the fetal circulation was initially accomplished by fetoscopy, a method of directly visualizing the fetus, umbilical cord, and chorionic surface of the placenta, using endoscopic instruments.  Fetoscopy for this purpose has now been replaced by ultrasound-directed percutaneous umbilical blood sampling (PUBS), also termed cordocentesis or funipuncture.  Fetal blood sampling is used in the prenatal evaluation of many fetal hematologic abnormalities such as hemophilia A, hemophilia B, or von Willebrand disease. In addition to hematologic studies, fetal blood samples can be used to diagnose autosomal recessive or X-linked immunologic deficiencies, including severe combined immunodeficiency (SCID), ChédiakHigashi syndrome, Wiskott-Aldrich syndrome, and chronic granulomatous disease.

95. Fetal blood chromosome analysis has been used to help clarify purported chromosome mosaicism detected in cultured amniotic fluid cells or chorionic villi. Rapid assessment of fetal chromosome complement has been accomplished by “direct” cytogenetic analysis of uncultured nucleated blood cells.86 Short-term fetal lymphocyte cultures can provide a cytogenetic result within 72 hours; direct analysis of spontaneously dividing fetal cells (probably nucleated red blood cells) can provide a karyotype result within 24 hours. This proves particularly useful for patients presenting late in the second trimester, when results from amniocentesis would be available only after pregnancy termination would no longer be available. Also, in cases of fetal structural abnormalities or intrauterine growth retardation (IUGR) presenting in the third trimester, rapid results may prove useful for decision making concerning the mode of delivery. More recently, fluorescent in situ hybridization (FISH) with chromosome- specific DNA probes has also been used for rapid prenatal diagnosis of aneuploidy using nucleated fetal blood cells from umbilical cord blood, as well as amniotic fluid cells.

96. FETAL TISSUE SAMPLING

97. Prenatal diagnosis of severe hereditary skin diseases (genodermatoses) used to require fetal skin biopsy for ultrastructural or immunohistochemical analysis. Such genodermatoses that have been amenable to diagnosis by fetal skin sampling have included:  anhidrotic ectodermal dysplasia,  bullous congenital ichthyosiform dystrophia (epidermolytic hyperkeratosis),  epidermolysis bullosa dystrophia (Hallopean- Siemens),  harlequin ichthyosis,  hypohidrotic ectodermal dysplasia,  epidermolysis bullosa lethalis,  nonbullous ichthyosiform erythroderma,  Sjögren-Larsson syndrome.

98.  1 stage -- collection of material for research in all of new-born and its delivery to the diagnostic laboratory  2 stage -- laboratory screening diagnostics belongs to the following stage of the mass screening program of new-born  3 stage -- clarification diagnostics of all cases with positive results got at screening  4 stage -- treatment of patients and regular medical check-up with the control of the course of treatment  5 stage -- m е dical genetic consulting of family