Genetic Counseling

1. Genetic Counseling By: Mahdi Bijanzadeh MD, PhD. bijanzadeh-m@ajums.ac.ir

2. Genetic counseling At the end of this session, you should answer this questions: 1. What is nondirective counseling? 2. What are basic rights of medical ethics? 3. What are steps of genetic counseling? 4. How we can detect risk of recurrence?

3. Genetic counseling • The first genetic counseling services ~ 40 years ago. • Definition: a process of communication & education that addresses concerns relating to development and/ or transmission of a hereditary disorder. • Counselor should try to ensure consultand to understand: 1. Medical diagnosis & its implications in terms of prognosis & possible treatment. 2. Mode of inheritance & risk of developing and/or transmitting it. 3. Choices or options available for dealing with risks.

4. Genetic counseling • Correct diagnosis, suitable treatment, patients and his/her family’s view about disease, ability to define & address the complex psychological issues. • Genetic counseling centers: genetic consultant, genetic nurse, support groups, electronic chat room. • Risk detection • Nondirective counseling: “scenario-based decision” • Just a few words spoken with genuine caring concern/ careless words …

6. Steps in genetic counseIing Establishing the diagnosis • The most crucial step, involves 3 fundamental steps: history, an examination, appropriate investigation (chromosome & molecular studies, referring). • Etiological heterogeneity: hearing loss & non-specific mental retardation. • Genetic heterogeneity: due to > 1 genetic mechanism:

7. Steps in genetic counseIing Calculating & presenting the risk 1. Quantification: numerical value • Odds or %: a risk of 1 in 4 can be presented as an odds ratio of 3 to 1 against, or as 25%. • Chance does not have a memory. • Not as prophet of doom: good side of coin should also be emphasize. 2. Qualification: nature of a risk • long-term burden, severity, curability, association with pain and suffering & availability of PND. 3. Placing risks in context: 1 in 40 of all babies has a congenital malformation (1/10…..1/20).

8. Steps in genetic counseIing Discussing the options • Probable PND and its details, IVF, AID, PGD. Communication and support • The ability to communicate is essential. • Agreeable, private & quiet, with ample time for discussion, … • Genetic register, patient support group.

10. Special problems Consanguinity • Average human carries between 1 & 2 genes for a harmful AR disorder, together with several mutations for lethality conditions before birth. • Cousins: 1/64+ 1/64= 1/32 + 1/40 = 1/20 • A slightly increased risk for a child with a multifactorial disorder.

11. Incest • First-degree relatives: >50% Adoption • Parents at high risk for a serious abnormality often express interest in adopting rather than that risk. • For offspring of consanguineous or incestuous matings, genetic risks can be given, althogh testing should not be undertaken unless this will be of direct medical benefit to the child.

12. Paternity • Until recently paternity could be disproved or excluded in 2 ways: possess a BG or other polymorphism not present in either mother or putative father/ if a child lacked a marker that putative father would have had to transmit to all of his children. • Genetic fingerprinting: using minisatellite minisatellite repeat sequence probes & SNPs.

13. Recurrent risk detection • One of the main goals of counseling. • Depends on 1. Genetic nature of disease 2. Pedigree 3. Genetics tests • Conditional probability • Categories: 1. Single gene (Mendalian) 2. Others • If she has Spina bifida: • If she has Down syndrome:

14. Mendalian, fully known genotype

15. Mendalian, alternative genotypes are possible • Variable risk, depends to whether proband is carrier or not? • C: 1/22 (general population risk)×1/4 • D: Bayesian analysis

16. - Obligate carrier - Bayesian analysis - Conditional probability Hemophilia A→ Mendalian, alternative genotypes are possible

17. Identify the possible scenarios

18. - Prior probability: depends to mutant allele receiption from parent. • - Conditional probability: depends to carrier of parent. • -Joint probability= Prior probability × conditional probability • -Posterior probability= Joint probability/∑ Joint probabilities

19. The probability that III5 is a carrier: • For every additional unaffected child born to II2: falls. • If III5 has unaffected son: falls. • If II2 has an affected child: she is carrier & for III5: 1/2 • If III5 has an affected child: she is carrier

20. Special items • - X linked lethal diseases: DMD • - Incomplete penetrance diseases: split-hand deformity • - Disorders with late age at onset: Parkinson disease (PD) • - Multifactorial diseases: empirical recurrence risk: !

21. Multifactorial examples

22. Consanguinity • No family history of AR condition: empirical risk. • Baseline risk for any abnormalities: 1.5-3% increases in the offspring of first cousins. • Not only for AR diseases, but also for all single gene and multifactorial disorders. • Any couple who has a child with a birth defect is at greater risk for having another child with a birth defect in a subsequent pregnancy.

23. Incidence of Birth Defects in children Born to Nonconsanguineous and First-cousin Couples

24. Ethics • Four basic rights of medical ethics: 1) Autonomy 2) Beneficence 3) Maleficience 4) Justice • Challenges between themselves and with social conditions and medical genetics should be balanced by ethicians.

25. Ethics • Genetic testing: - Prenatal diagnosis, especially for non-lethal diseases (MR, deafness, …), non-disease traits (IQ, personalities, cosmetic) or sex. SERIOUS DISORDER??? - Assisted reproductive technology - Testing asymptomatic adults for genotypes that predispose to late-onset disease: Huntington, Alzimer, Genetic breast cancer, Multifactorial diseases. INFORMED DECISION - Testing asymptomatic children for genotypes that predispose to adult-onset diseases: MCADD, carriers.

26. Ethics • Privacy of genetic information: - Duty to warn and permission to warn. • Misuse of genetic information: - Employment discrimination based on an employee’s genotype. - Discrimination in life and health insurance underwriting based on an employee’s genotype. • Adverse selection.

27. Ethics • Genetic screening: - Stigmatization - Privacy, psychologic disorders, - Coercion, insurance and employee problems. • Eugenics, nondirective counseling. • Dysgenics, reproductive compensation. • Genetics in medicine is about knowledge not for its own sake, but for the sake of improving health, relieving suffering and enhancing human dignity.

28. What is non-directive counseling? What are basic rights of medical ethics? What are steps of genetic counseling? How we can detect risk of recurrence?