Genetics in Primary Care: An Update

Transcription

1 Genetics in Primary Care: An Update September 11, 2018 Jagdeep S Walia, MBBS, FRCPC, FCCMG Head, Division of Medical Genetics, Director of Research, Department of Pediatrics, Queen s University

2 Financial Disclosures I have financial ties with new polyclinic called MEDICAL TREE, which is hiring family physicians and specialists Situated in West Kingston This talk not related to that clinic

3 Index Story of a patient Basic genetics Updates on Prenatal Genetics General genetics Cancer genetics Cardiogenetics Neurogenetics Pharmagenomics Nephrogenetics Geriatric genetics Hematology genetics.genetics.genetics.just kidding

4 Objectives After this presentation, the audience will be able to at least: 1. Describe the importance of family history 2. Describe NIPT and its use in primary care 3. Describe Variant of unknown significance and multi-gene panel tests

5 Genetics in Primary Care ~ One in ten of the patients seen in primary care has a disorder with a genetic component Three main themes of genetics in primary care: identifying patients with, or at risk of, a genetic condition clinical management of genetic conditions communicating genetic information Taking and considering a genetic family history is a key skill

6 Family History Jane (41) is 6 weeks pregnant Jane s husband Christopher (29) is an only child His parents William (60) and Margaret (59) are alive and well Jane has one brother John (34), he had one son David (10) to his first wife Alice (33). Their marriage ended in divorce John s second wife Christine (29) had a miscarriage at 9 weeks and a son Richard (4) who has CF Jane s father George Whitehead died at the age of 66 of colon cancer diagnosed at 50. Jane s mother Joan (64) is alive and well but had ovarian cancer at age 55 Supporting Genetics Education for Health

7 Family history: brush up Symbols 3 generation Ethnicity Consanguinity

8 Pedigree Symbols Male Marriage / Partnership (horizontal line) Female Person whose sex is unknown / Partnership that has ended P Pregnancy Offspring (vertical line) X weeks Miscarriage Affected Male & Female Parents and Siblings Carrier Male & Female Supporting Genetics Education for Health

9 Family History Jane (41) is 6 weeks pregnant Jane s husband Christopher (29) is an only child His parents William (60) and Margaret (59) are alive and well Jane has one brother John (34), he had one son David (10) to his first wife Alice (33). Their marriage ended in divorce John s second wife Christine (29) had a miscarriage at 9 weeks and a son Richard (4) who has CF Jane s father George Whitehead died at the age of 66 of colon cancer diagnosed at 50. Jane s mother Joan (64) is alive and well but had ovarian cancer at age 55 Supporting Genetics Education for Health

10 Joan William Hobson Margaret George Whitehead Died age 66 Dx 50 Joan 64 Dx 55 Christopher Hobson 29 Jane 41 Alice 33 John Whitehead 34 Christine 29 P 9 weeks Cystic Fibrosis 6 weeks David 10 Richard 4 Cystic fibrosis Colon Cancer Ovarian Cancer Supporting Genetics Education for Health

11 Updates on Prenatal Genetics NIPT Non-Invasive Prenatal Testing A new way to screen for specific chromosomes changes [mainly trisomy 21 (Down syndrome), but also trisomy 13, trisomy 18, and sex chromosomes X and Y] Google images

12 NIPT form

13 Family Physicians can order NIPT

14 Tests by Geneticists or MFM

15 Please note Nuchal translucency (NT) ultrasounds are still recommended in cases where NIPT is offered as a first-line screen (to be done without blood work for efts) If the NT measurement is 3.5mm please consider referral to Genetics immediately (do not wait for efts report as it will be positive) Self-pay NIPT is available to any patient who does not meet the above criteria; to be arranged through their obstetrical care provider. NIPT is considered a screening test, and no irrevocable decisions should be made based on this result alone.

16 Confirmatory tests Chorionic Villus Sampling Amniocentesis

17 Confirmatory Prenatal tests Type of procedure CVS Amniocentesis How is it done? Transcervical with ultrasound Transabdominal with ultrasound When is it done? 11+0 to 13+0 weeks 15+0 weeks Background risk of miscarriage (with no procedure done) 3-5% 2% Added risk of miscarriage (with procedure) 1 in 500 (0.2%) 1 in 1000 (0.1%) Type of testing done Length of time for results Accuracy of test results QFPCR (chromosomes 13, 18, 21, X and Y) Microarray Special genetic testing if needed within 1 week for QF-PCR/FISH 2-3 weeks for karyotype/microarray Other-dependent upon test 98-99% Small risk of placental mosaicism; when the cells in the CVS are not the same as the fetal cells about 1-2% of the time FISH (chromosomes 13, 18, 21, X, Y) Karyotype Special genetic testing if needed within 1 week for QF-PCR/FISH 2-3 weeks for karyotype/microarray Other-dependent upon test ~100%

18 Post-tests Patient given counseling for options if result is positive. We ask DFM residents to attend and later do that counseling as well.

19 Other part of the story -CF Joan William Hobson Margaret George Whitehead Died age 66 Dx 50 Joan 64 Dx 55 Christopher Hobson 29 Jane 41 Alice 33 John Whitehead 34 Christine 29 P 9 weeks Cystic Fibrosis Ovarian Cancer 6 weeks David 10 Richard 4 Cystic fibrosis Colon Cancer Supporting Genetics Education for Health

20 More of the story -CF This couple is at risk of having a child with CF Can be offered testing for CF panel Treatment options A lot of new treatment options now available Survival into 40s and 50s of affected individuals CF clinic in Kingston

21 Not done yet

22 There are more issues Joan William Hobson Margaret George Whitehead Died age 66 Dx 50 Joan 64 Dx 55 Christopher Hobson 29 Jane 41 Alice 33 John Whitehead 34 Christine 29 P 9 weeks Cystic Fibrosis Ovarian Cancer 6 weeks David 10 Richard 4 Cystic fibrosis Colon Cancer

23 Can There be a Hereditary Lynch Syndrome Cancer syndrome? Hereditary Ovarian Cancer syndrome Hereditary Breast and Ovarian cancer syndrome

24 Proportion of Hereditary CRC Familial ~15% Hereditary ~5% Lynch syndrome ~ 2-5% FAP ~ <1% Sporadic 80%

25 Lynch syndrome (HNPCC) Lynch syndrome is genetically heterogeneous Clinical testing available for 4 genes: MLH1 & MSH2 (most common), MSH6 & PMS2 Research testing may be available for other genes High penetrance Characterized by: Earlier onset than sporadic cancer More aggressive, proximal, right sided tumours Risk for extra-colonic tumours Distinct tumour pathology

26 Cancer Risk in Individuals with Lynch syndrome (HNPCC) to Age 70 Compared to General Population Cancer General Population Risk Lynch syn. Risk Mean Age of Onset in Lynch Colon 7 % 80% 45 years Endometrium 2.7% 20-60% 46 years Stomach <1% 11-19% 56 years Ovary 1.5% 9-12% 42.5 years Hepatobiliary tract <1% 2-7% 54 years Urinary tract <1% 4-5% ~55 years Small Bowel <1% 1-4% 49 years Brain / CNS <1% 1-3% 50 years from:

27 What Is New? Universal Screening for Colorectal Cancers for IHC coming soon

28 CRC with IHC results When to refer to genetics? IHC Immunohistochemistry If uncertain, refer! Image from Lynch syndrome screening network

29 Multi-gene panel testing for CRC 1 out of 6 (16%) have at least one hereditary cancer syndrome 1 out of 11 (8.7%) have Lynch syndrome 1 out of 12 (8%) have a hereditary cancer syndrome not typically associated with CRC

30 One more thing Ovarian Cancer in the family Further exploration Breast cancer in the maternal aunt at age 45

31 Hereditary Breast and Ovarian Cancer Multi-gene panels are becoming the standard of care Many different genes are associated with hereditary breast cancer Mutations in different genes can cause different breast cancer chances No mutation (average risk) Mutation in a moderate risk gene Mutation in a high risk gene Images: Myriad Genetics

32 Hereditary Breast and Ovarian Cancer Multi-gene panels are becoming the standard of care Guidelines for risk-reducing surgery and screening exist for some but not all of the genes on panels

33 VUS

34 Hereditary Cancer Multi-gene panels are becoming the standard of care Variants of unknown significance (VUS) continue to be challenging results in all genetic testing It is recommended that decisions regarding cancer screening and prevention be based on family history rather than a VUS.

35 A new term you may come across Allele frequency

36 Hereditary Cancer Tumor testing vs. Germline testing What is an allele? Image from NSGC Cancer SIG; Andrea Forman, CGC and S.tephany Connor, CGC

37 Hereditary Breast Cancer Test OCTANE STUDY Tumor testing vs. Germline testing Foundation ACT Test Bottom image from NSGC Cancer SIG; Andrea Forman, CGC and S.tephany Connor, CGC

38 Change the topic

39 Multifactorial diseases Diabetes, Psychiatric disorders, allergies, Autism etc are multifactorial disorders (mostly) which means there are genetic and environmental factors involved Recurrence risks are empiric

40 Direct-to-Consumer Testing Many companies provide DTC testing especially 23 and me Mostly have some SNP based testing Many studies have shown that for the same individual, the interpretation for genetics risks was variable.

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42 Let s talk about Genetics and Family Physicians

43 Flow of Genetic Information

44 Perspective of family physicians Can Fam Physician 2009

45 Result Can Fam Physician 2009

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48 Paneque et al. BMC Family Practice (2016)

49 Open Questions What shall we do to increase knowledge, confidence and satisfaction of primary care physicians for genetics education?

50 Resources GECKO - geneticseducation.ca NIH primary care genetics toolkit NHS GENE- EQUIPhttps:// page_id=152&lang=en