GENETICS PPT.pptx

GENETICS

1. GENETICS, GENETIC COUNSELLING AND TERATOLGY Merlin Mary James Tutor Faculty of Nursing Jamia Hamdard

2. Medical genetics is a relatively a new branch of an old science. Familial occurrences of specific traits have been cited in the literature. The era of molecular genetics was marked by the discovery of a molecular defect in the sickle cell disease, initially postulated by Linus Pauling in 1949. Genetics is the study of heredity. Heredity is a biological process where a parent passes certain genes onto their children or offspring. Every child inherits genes from both of their biological parents and these genes in turn express specific traits.

3. TERMINOLOGIES

4. SINGLE GENE INHERITANCE Single-gene traits are often called ‘ Mendelian ’ because like the garden peas studied by Gregor Mendel, they occur in fixed proportions among the offspring of specific types of mating . Single-gene disorders are primarily disorders of the pediatric age range greater than 90% manifest before puberty only 1% occur after the end of the reproductive period.

5. PATTERNS OF SINGLE GENE INHERITANCE

6. 4 BASIC PATTERNS OF SINGLE GENE INHERITANCE

7. AUTOSOMAL RECESSIVE Autosomal recessive is one of several ways that a trait, disorder, or disease can be passed down through families. An autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop. Information Inheriting a specific disease, condition, or trait depends on the type of chromosome that is affected. The two types are autosomal chromosomes and sex chromosomes. It also depends on whether the trait is dominant or recessive. A mutation in a gene on one of the first 22 nonsex chromosomes can lead to an autosomal disorder. Genes come in pairs. One gene in each pair comes from the mother, and the other gene comes from the father. Recessive inheritance means both genes in a pair must be abnormal to cause disease. People with only one defective gene in the pair are called carriers. These people are most often not affected with the condition. However, they can pass the abnormal gene to their children .

8. CHANCES OF INHERITING A TRAIT If you are born to parents who carry the same autosomal recessive change (mutation), you have a 1 in 4 chance of inheriting the abnormal gene from both parents and developing the disease. You have a 50% (1 in 2) chance of inheriting one abnormal gene . This would make you a carrier. In other words, for a child born to a couple who both carry the gene (but do not have signs of disease), the expected outcome for each pregnancy is: A 25% chance that the child is born with two normal genes (normal) A 50% chance that the child is born with one normal and one abnormal gene (carrier, without disease) A 25% chance that the child is born with two abnormal genes (at risk for the disease) Note: These outcomes do not mean that the children will definitely be carriers or be severely affected.

9. AUTOSOMAL DOMINANT Autosomal dominant is one of several ways that a trait or disorder can be passed down (inherited) through families. In an autosomal dominant disease, if you inherit the abnormal gene from only one parent, you can get the disease. Often, one of the parents may also have the disease.

10. Dominant inheritance means an abnormal gene from one parent can cause disease. This happens even when the matching gene from the other parent is normal. The abnormal gene dominates. This disease can also occur as a new condition in a child when neither parent has the abnormal gene. A parent with an autosomal dominant condition has a 50% chance of having a child with the condition. This is true for each pregnancy. It means that each child's risk for the disease does not depend on whether their sibling has the disease. Children who do not inherit the abnormal gene will not develop or pass on the disease. If someone is diagnosed with an autosomal dominant disease, their parents should also be tested for the abnormal gene.

11. AUTOSOMAL DOMINANT INHERITANCE, AD

12. AUTOSOMAL DOMINANT INHERITANCE, AD The gene concerned to single-gene disorder was located on an autosome, and the phenotype is dominant. It can be: Completely dominant Incompletely dominant Irregularly dominant Co dominant Delayed dominant Sex-influenced dominance

13. CHARACTERISTICS OF AUTOSOMAL DOMINANT INHERITANCE The phenotype usually appears in every generation, each affected person having an affected parent. Any child of an affected parent has a 50 percent risk of inheriting the trait. Phenotypically normal family members do not transmit the phenotype to their children. Males and females are equally likely to transmit the phenotype, to children of either sex. A significant proportion of isolated cases are due to new mutation

14. COMPLETELY DOMINANT: A phenotype expressed in the same way in both homozygotes and heterozygotes are completely dominant. Eg . Brachydactyly and Syndactyly type.

15. INCOMPLETELY DOMINANT : The phenotype due to a heterozygous genotype is different from the phenotype seen in both homozygous genotypes and its severity is intermediate between them. E.g., Achondroplasia : Improper development of cartilage at the ends of the long bones, resulting in a form of congenital dwarfism.

16. IRREGULAR DOMINANT: The phenotypes of some of the heterozygotes, for some reason, do not appear as affected. It can be seen as a skipped generation . Marfan Syndrome: it is a disorder of connective tissue involving a triad of ocular, skeletal and cardiovascular alterations. The most common ocular abnormality is a subluxation of the lens. Common skeletal findings include tall stature, arachnodactylic (spider-like) hands and feet and scoliosis. Severe scoliosis may compromise respiratory function in pregnant women with Marfan Syndrome. The major life threatening risk, however is the frequent occurrence of aortic fusiform or dissecting aneurysms. Fifty percent of aortic aneurysms in affected women under age 40occur during pregnancy with rupture most likely to occur during pregnancy.

17. CODOMINANT : Of or relating to two alleles of a gene pair in a heterozygote that are both fully expressed. Blood type-- type AB is codominant because both the antigen A and antigen B show up in the genotype.

18. DELAYED DOMINANT : The individual who carries mutant allele doesn’t onset until particular age. E.g., Huntington’s disease : it is an inherited disease that causes certain nerve cells in the brain to waste away. People are born with the defective gene, but symptoms usually don't appear until middle age. Early symptoms of HD may include uncontrolled movements, clumsiness or balance problems. Later, HD can take away the ability to walk, talk or swallow. Some people stop recognizing family members. Others are aware of their environment and are able to express emotions. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea, which is why the disease used to be called Huntington's chorea .

19. Sex-influenced dominance : The tendency for gene action to vary between the sexes within a species. For example, the presence of horns in some breeds of sheep appears to be dominant in males but recessive in females and baldness in human.

20. AUTOSOMAL RECESSIVE INHERITANCE

21.   AUTOSOMAL RECESSIVE INHERITANCE Autosomal recessive inheritance, AR: The gene concerned to single-gene disorder is located on an autosome, and the phenotype is recessive. Consanguinity : Relationship by blood or by a common ancestor. The chance that both parents are carriers of a mutant allele at the same locus is increased substantially if the parents are related and could each have inherited the mutant allele from a single common ancestor, a situation called consanguinity.

22. CHARACTERISTICS OF AUTOSOMAL RECESSIVE INHERITANCE An AR phenotype, if it appears in more than one member of a kindred, typically is seen only in the sibship of the proband , not in parents, offspring, or other relatives. For most AR diseases, males and females are equally likely to be affected. Parents of an affected child are asymptomatic carriers of mutant alleles. The parents of the affected person may in some cases be consanguineous. This is especially likely if the gene responsible for the condition is rare in the population. The recurrence risk for each sib of the proband is 1 in 4.

23. CYSTIC FIBROSIS : CF is a disorder of the cells that line the lungs, small intestines, sweat glands and pancreas. Sticky, thick mucus contributes to the destruction of lung tissue and impedes gas exchange in the lungs. It also prevents nutrient absorption in the small intestine, and blocks pancreatic ducts from releasing digestive enzymes. Cystic fibrosis (CF) is caused by a defect in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene makes a protein that controls the movement of salt and water in and out of the cells in your body. In people with CF, the gene does not work effectively.

24. MUCOPOLYSACCHARIDOSES : this diverse group of mucopolysaccharidoses accumulation disorders (MPS) encompasses 6 different sydromes whose primary types are: Hurler syndrome (type I), Hunter syndrome (type II), Sanfilippo’s syndrome (type III) and Mosquito syndrome (type IV). Individuals with these diseases exhibit coarse faces in infancy, short stature, skeletal and joint deformities, deafness, cornel clouding, umbilical hernia, progressive mental retardation.

25. PHENYLKETONURIA : is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it non-functional. This enzyme is necessary to metabolize the amino acid phenylalanine ( Phe ) to the amino acid tyrosine. When PAH activity is reduced, phenylalanine accumulates and is converted into  phenylpyruvate  (also known as phenylketone ), which is detected in the urine. Phenylalanine plays a role in the body's production of melanin, the pigment responsible for skin and hair color . Therefore, infants with the condition often have lighter skin, hair, and eyes than brothers or sisters without the disease.

26. SICKLE CELL DISEASE : or   sickle-cell anaemia   ( SCA ) is an autosomal   recessive   genetic   blood disorder   with   over dominance, characterized by   red blood cells   that assume an abnormal, rigid,   sickle   shape. Sickling decreases the cells' flexibility and results in a risk of various complications. The sickling occurs because of a mutation   in the   haemoglobin   gene. Life expectancy is shortened.

27. TAY- SACHS DISEASE : Tay–Sachs disease  (also known as  GM2 gangliosidosis or  hexosaminidase  A deficiency ) is a rare autosomal recessive genetic disorder. In its most common variant (known as infantile Tay–Sachs disease), it causes a progressive deterioration of nerve cells and of mental and physical abilities that commences around six months of age and usually results in death by the age of four. The disease occurs when harmful quantities of cell membrane components known as  gangliosides  accumulate in the brain’s nerve cells, eventually leading to the premature death of the cells. A ganglioside is a form of sphingolipid , which makes Tay–Sachs disease a member of the  sphingolipidoses . There is no known cure or treatment. Infants with Tay-Sachs disease appear to develop normally for the first few months of life. Then, as nerve cells become distended with fatty material, mental and physical abilities deteriorate. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in

28. X-LINKED RECESSIVE INHERITANCE

29. X-LINKED RECESSIVE INHERITANCE X-linked disorders whose causative gene is located on the X- chromosome

30. CHARACTERISTICS OF X-LINKED RECESSIVE INHERITANCE The incidence of the trait is much higher in males than in females. The gene responsible for the condition is transmitted from an affected man through all his daughters. Any of his daughters’ sons has a 50% chance of inheriting it. The gene is ordinarily never transmitted directly from father to son, but it is transmitted by an affected male to all his daughters. The gene may be transmitted through a series of carrier females; if so, the affected males in a kindred are related through females. Heterozygous females are usually unaffected, but some may express the condition with variable severity as determined by the pattern of X inactivation.

31. DUCHENNE’S MUSCULAR DYSTROPHY : it is a recessive X-linked form of muscular dystrophy, affecting around 1 in 3,600 boys, which results in muscle degeneration and eventual death.The disorder is caused by a mutation in the  dystrophin  gene, located on the human X chromosome, which codes for the protein  dystrophin , an important structural component within muscle tissue that provides structural stability to the  dystroglycan complex (DGC) of the cell membrane. While both sexes can carry the mutation, females rarely exhibit signs of the disease. Symptoms usually appear before age 6 and may appear as early as infancy. They may include: Fatigue Learning difficulties (the IQ can be below 75) Intellectual disability (possible, but does not get worse over time )

32. Muscle weakness Begins in the legs and pelvis, but also occurs less severely in the arms, neck, and other areas of the body Difficulty with motor skills (running, hopping, jumping) Frequent falls Trouble getting up from a lying position or climbing stairs Weakness quickly gets worse Progressive difficulty walking Ability to walk may be lost by age 12, and the child will have to use a wheelchair Breathing difficulties and heart disease usually start by age 20.

33. GLUCOSE -6- PHOSPHATE DEHYDROGENASE DEFICIENCY : it is usually asymptomatic until the affected male is exposed to one of many environmental triggers, such as certain drugs (antimalarial agents, aspirin, and sulphonamides) or certain foods (especially fava beans). Pregnancy in women with G6PD defiency (homozygotes) presents several complications. Haemolytic episodes are more frequent, urinary infections common in pregnancy, cannot be treated with sulpha based drugs and exposure of a fetus with G6PD deficiency may result in fetal hemolysis , hydrops fetalis and death. The incidence of anemia , hyperbilirubinemia and kernicterus is also increased among newborns with G6PD deficiency.

34. HEMOPHILIA A : Hemophilia A is an X-linked, recessive disorder caused by deficiency of functional plasma clotting factor VIII (FVIII), which may be inherited or arise from spontaneous mutation. The development of inhibitory antibodies to FVIII can result in acquired hemophilia A or can complicate the treatment of genetic cases. Depending on the level of FVIII activity, patients with hemophilia may present with easy bruising, inadequate clotting of traumatic injury or—in the case of severe hemophilia —spontaneous haemorrhage.

35. Signs of haemorrhage include the following: General : Weakness, orthostasis , tachycardia, tachypnea Musculoskeletal (joints): Tingling, cracking, warmth, pain, stiffness, and refusal to use joint (children) CNS : Headache, stiff neck, vomiting, lethargy, irritability, and spinal cord syndromes Gastrointestinal : Hematemesis, melena, frank red blood per rectum, and abdominal pain Genitourinary : Haematuria, renal colic, and post circumcision bleeding Other : Epistaxis, oral mucosal haemorrhage, hemoptysis , dyspnea (hematoma leading to airway obstruction), compartment syndrome symptoms, and contusions; excessive bleeding with routine dental procedures.

36. X-LINKED DOMINANT INHERITANCE

37. X-LINKED DOMINANT INHERITANCE An X-linked phenotype is described as dominant if it is regularly expressed in heterozygotes.

38. CHARACTERISTICS OF X-LINKED DOMINANT INHERITANCE Affected males with normal mates have no affected sons and no normal daughters. Both male and female offspring of female carriers have a 50% risk of inheriting the phenotype. For rare phenotypes, affected females are about twice as common as affected males, but affected females typically have milder (though variable) expression of the phenotype.

39. HYPOPHOSPHATEMIC RICKETS ( vitamin D-resistant rickets ): The ability of the kidney tubules to reabsorb filtered phosphate is impaired. Although both sexes are affected, the serum phosphate level is less depressed and the rickets less severe in heterozygous females than in affected males.

40. SEX CHROMOSOMES ABNORMALITIES GENOTYPE GENDER SYNDROME PHYSICAL TRAITS XXY, XXYY, XXXY Male Klinefelter Syndrome Sterility, small testicles, breast enlargement XO Female Turner’s Syndrome Sex organs don’t mature at adolescence, sterility, short stature XXX Female Trisomy X Tall stature, learning disabilities, limited fertility

41. GENETIC TESTING DEFINITION Genetic testing is defined as examining a sample of blood or other body fluids or tissue for bio-chemical, chromosomal, or genetic markers that indicate the presence or absence of genetic diseases.   It is also defined as a type of medical test that identifies changes in chromosomes, genes or proteins.

42. PURPOSES OF GENETIC TESTING

43. TYPES OF GENETIC TESTING

44. ETHICAL, LEGAL, AND SOCIAL ISSUES IN GENETIC TESTING Information from genetic testing can affect the lives of individuals and their families. In addition to personal and family issues, genetic disease or susceptibility may have implications for  employment  and  insurance . Therefore, careful consideration in the  handling  of this information is very important. Critical issues include: Privacy  - the rights of individuals to maintain privacy. Some genetic tests are required or strongly encouraged for developing fetuses and newborn babies. If an infant is found to be a carrier or likely to develop or be affected by an inherited disease, these findings may affect the future employability or insurability of the individual.

45. Informed consent  - obtaining permission to do genetic testing. One must have knowledge of the risks, benefits, effectiveness, and alternatives to testing in order to understand the implications of genetic testing. Confidentiality  - acknowledgment that genetic information is sensitive and access should to limited to those authorized to receive it. Future access to a person's genetic information also should be limited.

46. MEDICAL PROCEURE Genetic testing is often done as part of a genetic consultation and as of mid-2008 there were more than 1,200 clinically applicable genetic tests available .Once a person decides to proceed with genetic testing, a medical geneticist, genetic counselor , primary care doctor, or specialist can order the test after obtaining informed consent. Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a medical procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. Alternatively, a small amount of saline mouthwash may be swished in the mouth to collect the cells. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person's doctor or genetic counselor . Routine  newborn  screening tests are done on a small blood sample obtained by pricking the baby's heel with a lancet.

47. PRENATAL DIAGNOSIS AND SCREENING

48. COMMON DIAGNOSTIC TESTS

49. HUMAN GENOME PROJECT Begun formally in 1990, the US Human Genome Project was a 13 year old effort coordinated by the U.S. Department of Energy and the National Institutes of Health. The project originally was planned to last 15 years, but rapid technological advances accelerated the completion date to 2003.

50. PROJECT GOALS WERE TO

51. WHAT'S A GENOME?   WHY IS IT IMPORTANT? A   genome  is all the DNA in an organism, including its genes. Genes carry information for making all the proteins required by all organisms. These proteins determine, among other things, how the organism looks, how well its body metabolizes food or fights infection, and sometimes even how it behaves. DNA is made up of four similar chemicals (called bases and abbreviated A, T, C, and G) that are repeated millions or billions of times throughout a genome. The human genome, for example, has 3 billion pairs of bases.

52. The particular order of As, Ts , Cs, and Gs is extremely important. The order underlies all of life's diversity, even dictating whether an organism is human or another species such as yeast, rice, or fruit fly, all of which have their own genomes and are themselves the focus of genome projects. Because all organisms are related through similarities in DNA sequences, insights gained from nonhuman genomes often lead to new knowledge about human biology.

53. KEY FINDINGS OF GENOME PROJECT There are approximately 30,000genes in human beings, the same range as in mice and twice that of roundworms. All human races are 99.99% alike, so racial differences are genetically insignificant. This could mean all humans are descended from a single original mother. Most genetic mutation occurs in the male of the species and as agents of change. They are also more likely to be responsible for genetic disorders. Genomics has led to advances in genetic archaeology and has improved our understanding of how we evolved as humans and diverged from apes 25 million years ago. It also tells how our body works, including the mystery behind how the senses of taste works.

54. TWO FACTORS THAT MADE THIS PROJECT A SUCCESS ARE

55. ADVANTAGES OF HUMAN GENOME PROJECT

56. ANTICIPATED BENEFITS OF GENOME RESEARCH Improve diagnosis of disease. Detect genetic predispositions to disease. Create drugs based on molecular information. Use gene therapy and control systems as drugs design “custom drugs” (pharmacogenomics) based on individual genetic profiles MOLECULAR MEDICINE

57. Rapidly detect and treat pathogens (disease-causing microbes) in clinical practice. Develop new energy sources (biofuels). Monitor environments to detect pollutants. Protect citizenry from biological and chemical warfare. Clean up toxic waste safely and efficiently. MICROBIAL GENOMICS

58. Evaluate the health risks faced by individuals who may be exposed to radiation (including low levels in industrial areas) and to cancer-causing chemicals and toxins RISK ASSESSMENT

59. Study evolution through germline mutations in lineages. Study migration of different population groups based on maternal inheritance. Study mutations on the y chromosome to trace lineage and migration of males. BIOARCHAEOLOGY, ANTHROPOLOGY, EVOLUTION, AND HUMAN MIGRATION

60. Identify potential suspects whose DNA may match evidence left at crime scenes. Exonerate persons wrongly accused of crimes. Identify crime and catastrophe victims establish paternity and other family relationships. DNA IDENTIFICATION(FORENSICS)

61. Grow disease-, insect-, and drought-resistant crops. Breed healthier, more productive, disease-resistant farm animals.Grow more nutritious produce. Develop biopesticides . Incorporate edible vaccines incorporated into food products. AGRICULTURE, LIVESTOCK BREEDING, AND BIOPROCESSING

62. ETHICAL, LEGAL, AND SOCIAL ISSUES • Privacy and confidentiality of genetic information. • Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others. • Psychological impact, stigmatization, and discrimination due to an individual’s genetic differences. • Reproductive issues including adequate and informed consent and use of genetic information in reproductive decision making. • Clinical issues including the education of doctors and other health-service providers, people identified with genetic conditions, and the general public about capabilities, limitations, and social risks; and implementation of standards and quality‑control measures. • Uncertainties associated with gene tests for susceptibilities and complex conditions (e.g., heart disease, diabetes, and Alzheimer’s disease). • Health and environmental issues concerning genetically modified (GM) foods and microbes. • Commercialization of products including property rights (patents, copyrights, and trade secrets) and accessibility of data and materials.

63. GENETIC COUNSELLING DEFINITION Genetic counseling  is the 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. This complex process can be separated into diagnostic (the actual estimation of risk) and supportive aspects. Genetic Counseling…is a communication process which deals with problems associated with the occurrence or the risk of recurrence of a birth defect or a genetic disease in a family.

64. This process integrates: Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence. Education about inheritance, testing, management, prevention, resources Counseling to promote informed choices and adaptation to the risk or condition.

65. GENETIC COUNSELLING IS THE PROCESS OF Evaluating the results of this investigation Evaluating family history and medical records Helping parents understand and reach decisions about what to do next. Ordering genetic tests

66. COUNSEELING SESSION STRUCTURE The goals of genetic counselling are to increase understanding of genetic diseases, discuss disease management options, and explain the risks and benefits of testing. Counselling sessions focus on giving vital, unbiased information and non-directive assistance in the patient's decision making process.

67. Seymour Kessler, in 1979, first categorized sessions in five phases:

68. The intake and follow-up phases occur outside of the actual counselling session. The initial contact phase is when the counsellor and families meet and build rapport. The encounter phase/communication phase includes dialogue between the counsellor and the client about the nature of screening and diagnostic tests . The summary phase provides all the options and decisions available for the next step. If counselees wish to go ahead with testing, an appointment is organized and the genetic counsellor acts as the person to communicate the results.

69. INDICATIONS FOR GENETIC COUNSELLING

70. GENETIC COUNSELLORS A genetic counsellor is an expert with a Master of Science degree in genetic counselling. In the United States they are certified by the American Board of Genetic Counselling. In Canada, genetic counsellors are certified by the Canadian Association of Genetic Counsellors. Most enter the field from a variety of disciplines, including biology, genetics, nursing,  psychology , public health and social work.  Genetic counsellors should be expert educators, skilled in translating the complex language of genomic medicine into terms that are easy to understand.

71. Genetic counsellors work as members of a health care team and act as a patient advocate as well as a genetic resource to physicians. Genetic counsellors provide information and support to families who have members with birth defects or genetic disorders, and to families who may be at risk for a variety of inherited conditions . They identify families at risk, investigate the problems present in the family, interpret information about the disorder, analyse inheritance patterns and risks of recurrence, and review available genetic testing options with the family . Genetic counsellors are present at high risk or specialty prenatal clinics that offer prenatal diagnosis, paediatric care centres, and adult genetic centres. Genetic counselling can occur before conception (i.e. when one or two of the parents are carriers of a certain trait) through to adulthood (for adult onset genetic conditions, such as Huntington's disease or hereditary cancer syndromes).

72. PURPOSE Provide concrete, accurate information about inherited disorders. Reassure people who are concerned that their child may inherit a particular disorder that the disorder will not occur. Allow people who are affected by inherited disease to make informed choice about future reproduction. Educate people about inherited disorder and the process of inheritance. Offer support by skilled health care professionals to people who are affected by genetic disorders.

73. STEPS OF GENETIC COUNSELING History : A proper record of the history of the patient is necessary: This includes both present and relevant past history. Family history includes siblings and other relatives also. Obstetric history of includes exposure to teratogens (drugs, X-rays) in pregnancy. History of abortion or still birth if any, should be recorded Enquiry should be made about consanguinity as it increases the risk especially in autosomal recessive disorders. Pedigree Charting : At a glance this offers in a concise manner the state of disorder in a family. It forms an indispensable step towards counselling. Estimation of Risk : It forms one of the most important aspects of genetic counselling. It is often called recurrence risk. To estimate it one requires to take into account following points: Mode of inheritance Analysis of pedigree or family tree Results of various tests

74. Transmitting Information : After completing the diagnosis, pedigree charging and estimation of risk the next most important step is of communicating this information to the consultants. This important functioning involves various factors such as: Psychology of the patient. The Emotional stress under prevailing circumstances. Attitude of family members towards the patients. Educational, social and financial background of the family. Gaining confidence of consultants in subsequence meetings during follow up. Ethical, moral and legal implications involved in the process. Above all, communication skills to transmit facts in an effective manner i.e. making them more acceptable and palatable . Management : In genetics, “Treatment” implies a very limited scope. It naturally aims for prevention rather than cure. In fact for most of the genetic disorders cure is unknown. Treatment is therefore directed towards minimizing the damage by early detection and preventing further irreversible damage. For example in PKU, i.e. phenylketonuria. This disorder is characterized by a deficiency of phenylalanine hydroxylase enzyme, which is necessary for the conversion of phenylalanine to tyrosine.

75. PEDIGREE CHARTING OBTAINING A PEDIGREE A three generation family history should be a standard component of medical practice. Family history of the patient is usually summarized in the form of a pedigree

76. POINTS TO REMEMBER

77. PEDIGREE TERMINOLOGY Proband ( propositus or index case): is the affected individual through whom a family with a genetic disorder is first brought to attention. Consultand : the person who brings the family to attention by consulting a geneticist, may be an unaffected/affected relative of the proband . Brothers and sisters = sibs, and a family of sibs = sibship Kindred = the entire family. Relatives are classified 1 st degree, 2 nd degree, etc. Consanguineous = couples who have one or more ancestors in common Isolated case = if only one affected member in the kindred (= sporadic case if disorder in propositus is determined to be due to new mutation)

78. APPLICATIONS OF GENETIC COUNSELING Genetic counselors work with people concerned about the risk of an inherited disease or condition. These people represent several different populations 1. Prenatal Genetic Counselling : There are several different reasons a person or couple may seek prenatal genetic counselling. If a woman is of age 35 or older and pregnant, then there is an increased chance that her fetus may have a change in the number of chromosomes present. Changes in chromosome number may lead to mental retardation and birth defects. Prenatal tests that are offered during genetic counselling include Level II Ultrasound The maternal serum AFPChorionic Villus sampling (CVS) Amniocentesis. 2. Paediatric Genetic Counselling : Families or paediatricians seek genetic counselling when a child has features of an inherited condition. Any child who is born with more than one defect, mental retardation or dysmorphic features has an increased chance of having a genetic syndrome. A common type of mental retardation in males for which genetic testing is available is fragile X-syndrome.

79. 3. Adult Genetic Counselling :  Adults may seek genetic counselling when a person in the family decided to be tested for the presence of a known genetic condition, when an adult begins exhibiting symptoms of an inherited condition, or when there is a new diagnosis of someone with an adult-onset disorder in the family In addition, the birth of a child with obvious features of a genetic disease leads to diagnosis of a parent who is more mildly affected Genetic counselling for adults may lead to the consideration of presymptomatic genetic testing 4. Cancer Genetic Counselling : A family history of early onset breast, ovarian or colon cancer in multiple generations of family is a common reason a person would seek a genetic counsellor who works with people who have cancer. While most cancer is not inherited, there are some families in which a dominant gene is present and causing the disease A genetic counsellor is able to discuss the chances that the cancer in the family is related to a dominantly inherited gene. The counsellor can also discuss the option of testing for the breast and ovarian cancer genes.

80. ROLE OF A NURSE IN GENETIC COUNSELING Guiding a women or couple through prenatal diagnosis. Helping parents make decision in regard to abnormal prenatal diagnostic results. Assisting parents who have had a child with a birth defect to locate needed service and support. Providing support to help the family deal with the emotional impact of a birth defect. Coordinative services of other professionals, such as social workers, physical and occupational therapist, psychologist & dietician.

81. TERATOLOGY   Teratology is a specialized area of embryology. It is the study of the etiology of abnormal development (the study of birth defects). Developmental toxicity any morphological or functional alteration caused by chemical or physical insult that interferes with normal growth, homeostasis, development, differentiation, and/or behaviour. Teratogens therefore are xenobiotics and other factors that cause malformations in the developing conceptus . Examples of teratogens may include pharmaceutic compounds, substances of abuse, hormones found in contraceptive agents, cigarette components, and heavy metals. viral agents, altered metabolic states induced by stress, and nutrient deficiencies (e.g., folic acid deficiency).

82. PRINCIPLES OF TERATOLOGY Susceptibility to teratogenesis depends on the embryo’s genotype that interacts with adverse environmental factors (G × E interaction) The developmental stage of conceptus to the exposure determines the outcome. Teratogenic agents have specific mechanisms through which they exert there pathogenic effects. The nature of the teratogenic compound or factor determines its access to the developing conceptus /tissue. The four major categories of manifestations of altered development are death, malformation, growth retardation, and functional deficits. The manifestations of the altered development increase with increasing dose.

83.   THREE BASIC CHARACTERISTICS OF TERATOGENS

84. CRITICAL PERIODS Major fetal outcomes depend on the stage of pregnancy affected, as there are critical periods for the development of fetal processes and organs. One may divide the developmental stages in to three large categories: pre-implantation, implantation to organogenesis, and the fetal to neonatal stage. The outcomes associated with exposure during these periods vary. STAGE OF EXPOSURE OUTCOMES PRE-IMPLANTATION EMBRYONIC LETHALITY IMPLANTATION TO TIME OF ORGANOGENESIS MORPHOLOGICAL DEFECTS FETAL NEONATAL STAGE FUNCTIONAL DISORDERS, GROWTH RETARDATION, CARCINOGENESIS

85. SOME WELL KNOWN TERATOGENS THALIDOMIDE Thalidomide is a sedative-hypnotic drug used in Europe from 1957 to 1961. It was marketed for morning sickness, nausea, and insomnia . It went into general use and was widely prescribed in Europe, Australia, Asia, Africa, and the Americas. Women who had taken the drug from gestation days (GD) 35 to 50 gave birth to offspring suffering from a spectrum of different malformations, mainly amelia (absence of limbs) or phacomelia (severe shortening of limbs). Other malformations included: absence of the auricles with deafness, defects of the muscles of the eye and face, and malformations of the heart, bowel, uterus, and the gallbladder. The compound was withdrawn from the market in 1961 after about 10,000 cases had occurred.

86. ACCUTANE (ISOTETRINOIN) Accutane ( Isotetrinoin ) is a member of a family of drugs called retinoids , which are related to vitaminA . It is approved to treat serious forms of acne. These painful and disfiguring forms of acne do not respond to other acne treatments. Accutane can cause severe, life-threatening birth defects if the mother takes the medication during pregnancy. Even one dose of Accutane can cause major birth defects of the baby's ears, eyes, face, skull, heart, and brain. Women of child-bearing potential must have regular pregnancy tests before, during, and after taking isotretinoin . Accutane is available only under a special program called iPLEDGE .

87. DIETHYLSTILBESTROL (DES ) Diethylstilbestrol (DES) DES is a synthetic estrogen that inhibits ovulation by affecting release of pituitary gonadotropins. Some of its uses include treatment for hypogonadism , and in some cases of prostate cancer. From 1940 to 1970, DES was used to help maintain pregnancy. In utero exposure to DES has been associated with abnormal development of the uterus. It has also been associated with certain types of tumors . Women who were exposed in utero often developed vaginal neoplasia , vaginal adenosis , and cervical erosion. Effects were not seen in offspring until they reached puberty. Clear cell carcinoma of the vagina is a type of adenocarcinoma found in young women who are exposed to diethylstilbestrol in utero. The reproductive organ of males can also be affected subsequent to in utero exposure. The outcomes include hypotrophic testes, poor semen volume and quality.

88. ALCOHOL- “FETAL ALCHOL SYNDROME”: Alcohol- “ Fetal Alchol Syndrome” FAS is a pattern of mental and physical defects that develops in some offspring when exposed to alcohol in utero. The first trimester is the most susceptible period. Some babies with alcohol-related birth defects, such as lower birth weight and body size and neurological impairments, do not have all of the classic FAS symptoms. These outcomes are often referred to as fetal alcohol effects ( FAE). In addition to growth retardation, the most common outcomes of fetal alcohol syndrome include psychomotor dysfunction and craniofacial anomalies. Other infrequent outcomes include skeletal malformations such as deformed ribs and sternum, scoliosis, malformed digits, and microcephaly. Visceral deformities may also be present: heart defects, genital malformations, kidney, and urinary defects. A common concurrent manifestation of FAS include irregular arrangement of neurons and connective tissue.