1. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Practical Genetics for Primary Care Kate May Genetic Counsellor Nottingham Clinical Genetics Service, Nottingham City Hospital Telephone: 0115 9627728 Email: katherine.may@nuh.nhs.uk

2. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Overview Introduction to genetics for GPs Taking a family history Family cancer genetics Making a referral to the genetic department Sources of further information Ethical dilemmas

3. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Cumulative pace of gene discovery 1981-2003

4. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Genes and ill-health: for specialists only? Source: NHGRI 2006

5. Supporting Genetics Education for Health www.geneticseducation.nhs.uk When might a GP see genetics in practice? Clinical management Communicating genetic information Identifying patients

6. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Chromosomal disorders Syndromes: Down, Turner, Klinefelter. Chromosomal Translocations Autosomal dominant disorders Adult polycystic kidney disease Neurofibromatosis Huntington Disease Hypercholesterolemia Marfan Syndrome Familial Cancer Bowel/Uterine/Ovarian ?HNPCC Breast/Ovarian/Prostate ?BRCA1/2 Autosomal recessive disorders Cystic Fibrosis Haemoglobinopathies Haemochromatosis X-Linked disorders Duchenne and Becker Muscular dystrophies Haemophilia A Fragile X Variable inheritance patterns Deafness Muscular dystrophies Common / important conditions

7. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Questions a patient may ask What’s wrong? What does the future hold? Is there a cure? Why did it happen? Will it happen again? Will it be as bad or worse? Whose fault is it? Are there any tests? Who else is at risk?

8. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Why is the patient asking their question now? Recent diagnosis? Anniversary of a birth/death of an affected family member? Approaching the age others became affected? Screening becoming available? Planning marriage/beginning a family/buying a house? Pressure from family/friends? Religious aspects? Media reports about the condition?

9. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Is my baby at risk of cystic fibrosis?

10. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Scenario… Watch a video of a GP being consulted by Jane Hobson. She is in the early stages of pregnancy and is consulting him about the risks to her baby of having cystic fibrosis. Her nephew, Richard Whitehead, was diagnosed as having cystic fibrosis as a result of the neonatal cystic fibrosis screening programme. The medical family tree (pedigree) will be taken from Jane Hobson. Please draw out the pedigree as it is being taken.

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

12. Supporting Genetics Education for Health www.geneticseducation.nhs.uk CF video family history clip

13. Supporting Genetics Education for Health www.geneticseducation.nhs.uk George Died age 65, 2007 Joan 63 John Whitehead 27 Jane 29 Christine 30 Richard Born 2004 Cystic fibrosis 9 weeks Christopher Hobson 29 William 60 Joan 63 P 6 weeks Julie 27 David 10

14. Supporting Genetics Education for Health www.geneticseducation.nhs.uk From the family pattern, who must be carriers for cystic fibrosis? George Whitehead Died age 65, 2007 Joan 63 John Whitehead 27 Jane 29 Christine 30 Richard Born 2004 Cystic fibrosis 9 weeks Christopher Hobson 29 William 60 Joan 63 P 6 weeks Julie 27 David 10

15. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Is the probability of Jane Hobson being a carrier for cystic fibrosis sufficiently high to offer testing? or George Died age 65, 2007 Joan 63 John Whitehead 27 Jane 29 Christine 30 Richard Born 2004 Cystic fibrosis 9 weeks Christopher Hobson 29 William 60 Joan 63 P 6 weeks Julie 27 David 10

16. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Assume Jane was tested and found to be a carrier. What is the probability that the baby in Jane and Christopher Hobson’s current pregnancy will have cystic fibrosis? George Died age 65, 2007 Joan 63 John Whitehead 27 Jane 29 Christine 30 Richard Born 2004 Cystic fibrosis 9 weeks Christopher Hobson 29 William 60 Joan 63 P 6 weeks Julie 27 David 10

17. Supporting Genetics Education for Health www.geneticseducation.nhs.uk At what stage should specialist genetic advice be sought? George Died age 65, 2007 Joan 63 John Whitehead 27 Jane 29 Christine 30 Richard Born 2004 Cystic fibrosis 9 weeks Christopher Hobson 29 William 60 Joan 63 P 6 weeks Julie 27 David 10

18. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Genetic family history 1. Why is family history information important to my practice? 2. How do I collect and record family history information? Factsheets, animations, slides and videos ‘Medical Family History Drawing Tool’ Worksheets for practising drawing pedigrees 3. How do I interpret family history information? Factsheets and slides on ‘Understanding Modes of Inheritance’’ Factsheets and worksheets on ‘Interpreting a Family History’

19. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Familial Cancer Genetics When to make a referral Who to refer to Sources of information and advice

20. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Dominant breast cancer genes BRCA1 and BRCA2 identified. Possibly BRCA3 and others? Lifetime risk of breast cancer 50 - 85% Carry risk of other cancers; ovary (BRCA1 44%, BRCA2 27%), and a slightly increased risk prostate and some other cancers

21. Parents Gametes At conception Autosomal Dominant Inheritance AffectedUnaffected

22. Cancer Hereditary gene change 1 Somatic mutation Normal Tissue Somatic mutation

23. Cancer Hereditary gene change Somatic mutation Cancer 2 Somatic mutations

24. Supporting Genetics Education for Health www.geneticseducation.nhs.uk What factors do you think may indicate a woman is at higher risk of breast / ovarian cancer?

25. Case 1 55 Breast cancer 46 Kay 65 76 49 51 53 70 Low risk – manage in primary care Older age of onset Different sides of the family Reassure and explain population risk, advise on symptom awareness and to report any changes in family history

26. Case 2 32 Janet Breast cancer Ovarian cancer Refer –high risk Different generations Young age onset Equal transmission through men Multiple tumours in one individual Breast and ovarian cancer 35 48 breast cancer 56 ovarian cancer 42 Refer – to Wendy Chorley (familial cancer service) – Royal Derby Hospital. They will offer a referral to genetics where indicated.

27. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Familial Colorectal Cancer Colorectal cancer common – 1 in 25 5-10% strong genetic contribution The most important of these genetic syndromes are: - familial adenomatous polyposis(FAP) - hereditary non-polyposis colorectal cancer (HNPCC) Most dominant – not all!

28. Case 3 73 32 Peter 75 60s 78 73 43 77 35 died in war 68 Colorectal cancer Refer –moderate risk Young age of onset (under 45) Refer to Wendy Chorley Familial Cancer Service Royal Derby Hospital - first degree relatives offered bowel screening. No genetic testing available

29. Case 4 Colorectal cancer Endometrial cancer 8075 69 55 78 48 42 George 49 42 30 Martin 39 Polyps Refer –high risk Young age of onset Endometrial and bowel cancers (other related cancers include ovarian, ureteric, renal pelvis, gastric) Two generations Polyps Refer to Wendy Chorley - diagnoses would be confirmed, offer genetic testing to George. Bowel screening would be offered to at-risk family members.

30. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Assessing cancer risk Young age of onset, pattern of similar tumours in a family (or multiple primaries in one person) Related tumours Remember ethnicity e.g. Chinese, Indian, Ashkenazi Jewish ancestry Use national / local guidelines e.g. NICE familial breast cancer Over 200 hereditary cancer syndromes described – individually rare Contact the CGS if you are unsure

31. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Making a referral to clinical genetics Information needed –Patient’s name, D.O.B, address, GP –date of last period or due date (if pregnant) –Details of concern, name of affected person and D.O.B if possible and how they are related to your patient. –Patient’s telephone number – home and daytime contact

32. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Making a referral to clinical genetics Most referrals can be sent by post or C&B Urgent referrals should be made by telephone A referral is urgent if –The patient is pregnant –The patient is in the last stages of a terminal illness

33. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Sources of information Local or national guidelines e.g NICE Discussing with a colleague Contact the local CGS Internet

36. Supporting Genetics Education for Health www.geneticseducation.nhs.uk National Genetics Education and Development Centre

37. Supporting Genetics Education for Health www.geneticseducation.nhs.uk

38. Supporting Genetics Education for Health www.geneticseducation.nhs.uk

41. Supporting Genetics Education for Health www.geneticseducation.nhs.uk To refer or not refer? Please call Nottingham Regional Clinical Genetics Service for advice and information Tel: (0115) 9627728

42. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Referral Address Nottingham Clinical Genetics Service, City Hospital Campus, The Gables, Gate 3, Hucknall Road Nottingham NG5 1PB Tel 0115 9627728

43. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Ethical Issues in Primary Care Genetics

44. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Mr P was recently diagnosed with autosomal dominant polycystic kidney disease (ADPKD). Having realised that each of his children has a 50% chance of having inherited the condition from him, Mr P asks his GP to organise a kidney ultrasound for his two children aged 10 and 7, to see if they have inherited the condition. The GP should do so. Strongly agree AgreeNeutralDisagreeStrongly disagree Consider the statement above and indicate the extent to which you agree or disagree with it.

45. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder affecting approximately 1 in 3000 male births. Boys with DMD are usually diagnosed between 4-5 years of age. In about two thirds of cases, the boy’s mother is a carrier for the condition, and at risk of having another affected boy. There is no cure for DMD. Neonatal screening of all male births should be performed to identify affected boys so that their mothers can be tested to see if they are a carrier and therefore at risk of having further affected children. Consider the statement above and indicate the extent to which you agree or disagree with it. Strongly agree AgreeNeutralDisagreeStrongly disagree

46. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Erica is 35 and registers as a new patient at her GP surgery. When registering, Erica is asked if she has any family history of concern, and states that she does not. Erica's paternal aunt Eve is also registered with the GP practice, but the two branches of the family have no contact. The GP recognises their unusual surname and remembers speaking with Eve about her strong family history of breast cancer. Upon checking his records, the GP realises that Erica will be at risk of carrying the BRCA1 genetic change in the family. The GP has an obligation to tell Erica, his new patient, information which he knows may affect her health and access to screening in the future. Strongly agree AgreeNeutralDisagreeStrongly disagree Consider the statement above and indicate the extent to which you agree or disagree with it.

47. Supporting Genetics Education for Health www.geneticseducation.nhs.uk John and Susan come in to your surgery. You have seen quite a lot of them over the past two years, as their second child Michael was born with Sickle Cell Anaemia. They have recently had another child, Rebecca. Newborn screening showed that Rebecca is a carrier of sickle cell anaemia, and this information was routinely reported to parents. John and Susan also have a healthy older daughter, Mary, 8yrs. Her carrier status is unknown, as screening of newborns was not yet done routinely when she was born. As they already have one ill child and one carrier child, John and Susan are also quite anxious about Mary's carrier status for this condition. They request that you organise a referral for carrier testing. What should you do? TestUncertainNot test

48. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Jane is a healthy, 24 year old patient. She comes to speak to you about her family history of Huntington Disease (HD, an autosomal dominant condition), explaining that her maternal grandmother was affected and died 1 year ago, in her 60s. Jane is aware that genetic testing is available to her family, and Jane wishes to request this, to determine if she will develop the condition herself in the future. You ask Jane how her mother feels about this issue, and Jane tells you that her mother has declined genetic testing. If Jane is tested and shown to have an expansion which causes HD, you will also have clarified that her mother will develop HD. Jane should not be offered genetic testing without first testing her mother. Strongly agree AgreeNeutralDisagreeStrongly disagree

49. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Thanks so much for your time! Kate May Genetic Counsellor Nottingham Regional Clinical Genetics Service, Nottingham City Hospital Telephone: 0115 9627728 Email: katherine.may@nuh.nhs.uk

50. Supporting Genetics Education for Health www.geneticseducation.nhs.uk Current and future developments Screening technology e.g. non invasive techniques Genetic profiling – genomic medicine New technology in assisted reproduction Treatments for genetic and non-genetic disorders - Stem cells - Gene therapy