1. GENETIC COUNSELING Munir I Malik M.D.

6. What is genetic counseling Education and guidance given (to parents) by professional advisors to help them understand the disease and to make informed decisions

7. AIM To reduce the risk of genetic diseases in the population and better management of those who already have the disease

8. Clients Parents of a child with birth defect to learn about – 1. prognosis of the effected child and – 2. chances of defect in subsequent pregnancies People with genetic defects in the family People who are diagnosed to be heterozygotes for a recessive gene defect

9. Steps in Genetic Counseling Diagnosis Risk assessment Communication and discussion of options Long-term contact and support

10. Step 1; Diagnosis History Family History Pedigree chart Physical examination Lab. Investigations Chromosomal analysis DNA testing

11. Genetic Testing It is used to Clarify a diagnosis for appropriate treatment and prognosis Allow families to avoid having children with devastating diseases Identify people at high risk for certain conditions

13. Types of Genetic Tests Diagnostic/Confirmatory testing Used to identify or confirm the diagnosis of a disease or condition in an affected individual. Helpful in predicting the course of a disease and determine the choice of treatment Predictive Testing Determines the probability of the disease in a healthy individual with or without a family history of the disease

14. Types of Genetic Tests Carrier Testing – Performed to determine whether an individual carries – a copy for a particular recessive disease. It is usually – done before a pregnancy occurs. Newborn Screening – Performed in newborns, usually as part of state public – health programs, to detect certain genetic diseases – where early diagnosis and treatment are available

15. Prenatal testing Amniocentesis The most common test prenatal test performed today (Morris, 1993) Estimated Fetal loss during procedure is 0.5%(O’Connor, 1989) Done between 14 th to 17 th week Chorionic Villi Sampling Can be performed at a much earlier age of the fetus compared to an amniocentesis test. Done during 5 th week Pre-implantation diagnosis Used after in vitro fertilization to diagnose a genetic disease or condition in a pre-implantation embryo Maternal blood test during pregnancy Alpha-fetoprotein Sampling

16. Step 2; Risk assessment Determine risk of chromosomal or genetic mutation in a family Autosomal dominant Autosomal recessive Sex linked recessive Multifactorial Mutations Unidentified gene defects

18. STEP 3: Communication and Decision making Provide knowledge Allow couples to understand mode of inheritance and medical consequences of the disease including transmission Help them make a decision Discuss all possible options with their benefits and harms

20. points to remember Glass is (almost) always half full. Give good news before bad news Assess the emotional state of the parents. You may need more than one session Educational level of parents matter a lot. Talk in language they can understand Help them make an ethical decision Keep in mind social/cultural/religious background of your patient

21. Points to Remember provide consultands with all information needed to arrive at their own informed decision details of all the choices open to them - include a complete discussion of reproductive options alternative approaches to conception - AID, donor ova review of techniques, limitations and risks associated with methods available for prenatal diagnosis

22. Communication and Support Communication - two way process Counselor provides information Receptive to fears and aspirations: expressed or unexpressed by consultant Information - present in clear, sympathetic and appropriate manner

23. Pedigrees for autosomal disorders – An affected child from 2 unaffected parents indicates an autosomal recessive trait Counselor can suggest genetic testing – Two affected parents produce an unaffected child Indicates both parents are heterozygous for an autosomal dominant trait Another indicator- when both parents are unaffected, none of their children are either – Study the two pedigrees on the following slides

27. Pedigrees for sex-linked disorders – X-linked disorders X-linked recessive disorders – To be affected, daughters must inherit it from both parents – Sons can only inherit it from mother, therefore more males affected than females X-linked dominant disorders – Affected males pass the trait only to daughters – Females can pass trait to both daughters and sons – Y-linked disorders Present only in males Fathers pass trait to all sons – Study the pedigree on the following slide

28. X-linked recessive disorders – Color blindness About 8% of Caucasian males have red-green colorblindness – Duchene's muscular dystrophy Absence of a protein called dystrophin – Causes calcium to leak into muscle cells which actives enzymes that break down the cells – Hemophilia Hemophilia A is due to a lack of clotting factor VIII Hemophilia B is due to a lack of clotting factor IX Blood clots slowly or not at all

29. Autosomal dominant disorders – Marfan syndrome Defect in fibrillin-protein in elastic connective tissue – Long limbs and fingers, weakened arteries, dislocated lenses in the eyes – Huntington disease Progressive degeneration of brain cells Gene for defective protein called Huntington – Too many copies of the amino acid glutamine

30. Autosomal recessive disorders cont’d. – Phenylketonuria Lack enzyme for phenylalanine metabolism Affects nervous system development – Sickle-cell anemia Irregular red blood cells caused by abnormal hemoglobin – Clog vessels- poor circulation – Internal hemorrhaging Heterozygous individuals are normal unless dehydrated or experience mild oxygen deprivation Genetic disorders of interest – Autosomal recessive disorders Tay-sachs disease – Jewish people in U.S. of central and eastern European descent – Lack of hexosaminidase A » Glycosphingolipid stored in lysosomes » Build up in brain cells-loss of function – Symptoms appear in infancy Cystic fibrosis – Most common genetic disorder in Caucasians in U.S. – Defect in chloride channel proteins in cells – Thick, abnormal mucus production » Lungs, bronchial tubes, pancreatic ducts affected

31. Thank you Questions ?