Introduction to Medical Genetics Unit 8 - 2007

1. Introduction to Medical GeneticsUnit 8 - 2007 David S. Rosenblatt, M.D. david.rosenblatt@mcgill.ca

2. Medical GeneticsPractice Profile Syndromology Inherited Metabolic Disease Prenatal Diagnosis Cancer Genetics Neurogenetics Psychiatric Genetics Cytogenetic, Molecular Genetic, and Biochemical Genetics laboratory services

3. Medical Genetics-Syndromology Children and adults with dysmorphic features (physical findings that alter appearance) Children and adults with syndromes (conditions with physical and/or laboratory findings that occur together in recognizable patterns) Diagnosis and genetics counselling. Important for prognosis and reproductive counselling and also treatment.

4. Pediatric Genetics Birth defects (CHD, NTD, CL/CP) or multiple malformations Dysmorphic features Metabolic disease Chromosomal abnormalities Mental retardation, devel. delay A 2nd clinical settingA 2nd clinical setting

5. Pediatric Genetics Ambiguous genitalia, abnormal sexual development Unexplained hearing/visual loss Abnormal stature (short, tall, disproportionate) or growth pattern (asymmetric) Consanguinity

6. Medical GeneticsInherited Metabolic Disease Newborn Sreening (e.g. PKU) Neonatal onset Sudden infant death (e.g. MCAD) Childhood onset Adolescent onset Adult onset Opportunities for prevention, diagnosis and management

7. Medical GeneticsPrenatal Diagnosis Screening: Maternal serum, ultrasound Diagnosis: ultrasound, MRI, aminocentesis, chorionic villus biopsy, biochemical analysis, molecular analysis Treatment: Early delivery, fetal surgery Genetic counselling: Options for pregnancy and recurrent risks.

8. Prenatal Diagnosis Indications for referral: Increased risk chromosome abnormality Advanced maternal age Abnormal (positive) results of screening Previous child with a chromosome abnormality

9. Prenatal Diagnosis Indications for Referral: Teratogen exposure Family history of other genetic disorder or malformation Infertility Multiple miscarriages Azoospermia in the male partner � requires MESA � ICSI - IVFMultiple miscarriages Azoospermia in the male partner � requires MESA � ICSI - IVF

10. Abnormal findings on ultrasound

11. Genetic Counselling in Prenatal Diagnosis Information giving Psychological counselling Decisions TOP often late (DMD) Follow up care Referrals For those who choose to continue their pregnanciesFor those who choose to continue their pregnancies

12. Medical GeneticsCancer Genetics Breast Cancer (BRCA) Colon Cancer (FAP and HNPCC) Cancer Syndromes (many) Prevention, diagnosis, treatment Genetic counselling and testing

13. Cancer Genetics Clues to cancer syndromes: Multiple family members Bilateral Early onset Multiple primaries Rare cancers Another very important area in medical gentics is cancer geneticsAnother very important area in medical gentics is cancer genetics

14. Cancer Genetics

15. Medical GeneticsNeurogenetics Developmental delay (mental retardation) Epilepsy Syndromes (many neurological) Metabolic (many metabolic disease: particular involvement with mitochondrial and neuromuscular disease) Movement disorders (Hereditary ataxias)

16. Adult Genetics Adult-onset conditions Huntington�s AD Alzheimer�s Psychiatric disease

17. Medical GeneticsPsychiatric Genetics Schizophrenia Bipolar disease Alcoholism Autism Limited clinical application at present

18. Adult Genetics Myriad other indications Bleeding disorders Unusual dermatological findings Sudden cardiac death Connective tissue disorders All of the indications for pediatric genetics if they present in adulthood, plusAll of the indications for pediatric genetics if they present in adulthood, plus

19. Marfan Syndrome Error in Fibrillin Gene Causes problems in Connective Tissue skeleton, eyes, heart and blood vessels, nervous system, & skin Affects 1/5000 people Arm Span longer than height Joint ultra flexable Pectus concavous Dilation of the Aorta � The aorta gets small weak spots that bulge out and can break Arachnodactyly � Long fingers Error in Fibrillin Gene Causes problems in Connective Tissue skeleton, eyes, heart and blood vessels, nervous system, & skin Affects 1/5000 people Arm Span longer than height Joint ultra flexable Pectus concavous Dilation of the Aorta � The aorta gets small weak spots that bulge out and can break Arachnodactyly � Long fingers

20. Medical GeneticsClinical Laboratory Cytogenetics Biochemical Genetics Molecular Genetics

21. Medical Genetics & Family MedicineToday and Tomorrow Family History (online resources for families: https://familyhistory.hhs.gov/) Be alert-first contact with patient and family Be aware of resources Predisposition to common disease (heart disease, asthma) Follow families and ensure continuity of care

22. Medical Genetics & Specialty Medicine Today and Tomorrow Family history Expertise in specific areas of genetic medicine Opportunities for fellowships in clinical or clinical laboratory genetics New therapies (gene therapy, stem cells) Common disease (Role of Genomics)

23. Cautions and Challenges Be aware of GenoHYPE (Not everything is ready for �prime time� Avoid cynicism (Advances have already and will in the future lead to better care) Use resources (OMIM, PubMed, Genetest, Geneclinics etc) Genetics and genomics will be part of your practice no matter what you choose

24. Department of Human Genetics: Clinical Training Royal College of Physicians and Surgeons of Canada College of Physicians of Quebec Canadian College of Medical Geneticists (also certifies PhD Medical Geneticists � primarily as laboratory director)

25. CCMG Training Entry after M.D. and core training or after Ph.D. in Genetics. Most candidates train for 2 years to become laboratory directors in either cytogenetics, biochemical genetics, or molecular genetics. Rarely, Ph.D. trains for 2 years as clinical geneticist.

26. RCPSC and CMQ Training in Medical Genetics Medical Genetics is a Primary Specialty-entry is directly from medical school. Residency is for a period of 5 years with the first two core years in pediatrics, medicine and high risk obstetrics. Exposure to biochemical, cytogenetic and molecular genetic laboratories in year 3. Exposure to all other aspects of Medical Genetics in years 3, 4 and 5.

27. Definition A communication process dealing with the human problems associated with the occurrence, or the risk of occurrence, of a genetic disorder in a family. Am J Hum Genet 1975: 27:240-242

28. Definition Help the individual or family to: Comprehend the medical facts (dx, course, management) Appreciate the role of heredity and individual risks Understand the alternatives for dealing with risks

29. Definition Help the individual or family to: Choose a course of action in accordance with their risk, family goals, and ethical and religious standards Make the best possible adjustment to the situation

30. Counselling Contexts and Situations Prenatal and preconceptional Pediatrics Adult - incl. familial cancers

31. The genetic counselling process What goes on in a genetics evaluation?

32. The Medical Genetics Evaluation 1. �Contracting� � why there? 1. History Taking sometimes by questionnaire 2. Physical exam 3. Risk assessment 4. Diagnostic studies 5. Counselling 6. Follow up Often the GC begins the session alone with the patient, and performs what we call �contracting�. Sometimes no idea why they are there! Prepare to give bad news: Find out how much they know � how much they want to know � before approaching session. Often the GC begins the session alone with the patient, and performs what we call �contracting�. Sometimes no idea why they are there! Prepare to give bad news: Find out how much they know � how much they want to know � before approaching session.

33. Genetic counsellors: Strive to be nondirective, culturally sensitive Consider the family as patient, eg translocation carriers Pay extra attention to psychosocial dimensions � support, eg pregnant patient with CF

34. Challenges Testing may -> insurance, employment discrimination Costs (BRCA sequencing ~US $4,000) Inconclusive or negative results Testing of minors � parents want; ethicists don�t Nonpaternity Other ethical issues � rights of the disabled It�s difficult to make a SHORT list of the challengesIt�s difficult to make a SHORT list of the challenges

35. Challenges Field evolving rapidly Duty to recontact? Diagnoses can be changed (SLO -> unknown) Process is time consuming Must introduce many new concepts Decision making in crisis Lack of primary care providers Needs of the population Requires giving bas news on a regular basisRequires giving bas news on a regular basis