‘Genetics in Primary Care’ - Derby GP Specialty ：“基因在初级保健的德比GP专业.ppt

Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Practical Genetics for Primary Care,6th February 2013 Marie-Anne OReilly Genetic Counsellor Nottingham Clinical Genetics Service Email: ,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,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,When might a GP see genetics in practice?,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 ?Lynch 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,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Other common referral reasons,Developmental delay Autism / Asperger / Autistic spectrum Seizures FH hearing loss / visual problems Recurrent miscarriage Pregnancy issues (e.g. differences noted on scan),Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Questions a patient may ask,Whats 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?,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Why is the patient asking their question now?,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?,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,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Male,Female,Person whose sex is unknown,Pregnancy,Marriage / Partnership (horizontal line),Parents and Siblings,Offspring (vertical line),Affected Male & Female,Carrier Male & Female,Partnership that has ended,Pedigree Symbols,Miscarriage,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,SB,Unaffected person, sex unknown,Twins:,identical;,non-identical,Double line shows consanguineous couple,Stillborn baby, unknown sex,Therapeutic abortion,Affected male,Unaffected female who has died,Affected female,Spontaneous abortion,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Is my baby at risk of cystic fibrosis?,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.,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,CF video family history clip,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,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,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?,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 Hobsons current pregnancy will have cystic fibrosis?,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,At what stage should specialist genetic advice be sought?,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Now! Need to identify familial mutations Need to test partner to clarify risks,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,N/N,N/dF508,N/dF508,dF508/dF508,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Pre-conceptual Counselling,Is the ideal situation- facilitates optimal counselling and choice. Patient will want to know: Inheritance pattern Might they be affected? What is the risk for the future children? What options are available for pregnancy? Prenatal diagnosis Fetal sexing on blood for X-linked conditions PGD for monogenic conditions and chromosome translocations (NHS service if no healthy child) What are the pros and cons of the options? What will happen during a pregnancy? At what gestations? Who will organise tests and give results?,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Familial Cancer Genetics,Inheritance patterns When to make a referral Who to refer to Sources of information and advice,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Dominant breast cancer genes,BRCA1 and BRCA2 identified and clinical testing available. Possibly 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,Parents,Gametes,At conception,Autosomal Dominant Inheritance,Affected,Unaffected,Cancer,Normal Tissue,Cancer,Cancer,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Assessing risk where there is a history of cancer Cases,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?,Case 1,55,Breast cancer,46 Kay,65,76,49,51,53,70,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,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,Case 2,32 Janet,Breast cancer Ovarian cancer,35,48 breast cancer 56 ovarian cancer,42,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,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.,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) - Lynch Syndrome, or hereditary non-polyposis colorectal cancer (HNPCC) Most dominant not all!,Case 3,73,52 Peter,75,60s,78,73,63,77,35 died in war,68,Colorectal cancer,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Case 3,73,52 Peter,75,60s,78,73,63,77,35 died in war,68,Colorectal cancer,Low risk reassure- advise on symptom awareness and reporting. FOB testing from 60y.,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Case 4,73,40 Peter,75,60s,78,73,43,77,35 died in war,68,Colorectal cancer,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Case 4,73,40 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 Familial Cancer Service Royal Derby Hospital. 1st degree relatives offered bowel screening. Tumour investigations may be possible to clarify condition.,Case 5,Colorectal cancer,Endometrial cancer,80,75,69,55,78,48,42 George,49,42,30 Martin,39 Polyps,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Case 5,Colorectal cancer,Endometrial cancer,80,75,69,55,78,48,42 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.,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,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Cancer referrals,Family cancer team (01332 785771) Wendy Chorley: breast and bowel Diana Mayor: breast Samantha Crockett: ovary Direct referrals to genetics: Known gene in the family Unclear pattern of cancers / rare cancers Other cancer cases: Refer to family cancer team initially,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Making a referral to clinical genetics,Information needed Patients 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. Patients CURRENT telephone number home and daytime contact (check mobile!),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,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,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,National Genetics Education and Development Centre,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Other things we do,Provide open access for questions (will still need re-referral for new episode of care) Support groups if appropriate (Contact-a-family) Refer on e.g. for screening, CAMHS Offer research participation (BOCS/CORGI/DDD),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 962 7728 email: See our website for referral guidelines: https:/www.nuh.nhs.uk/our-services/services/genetics/clinical-genetics/,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 962 7728 Fax: 0115 962 8042,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Confidentiality: Ethical Issues in Primary Care Genetics,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Huntington Disease,Neurological condition affecting cognition and co-ordination and mood Autosomal dominant inheritance Variable onset, (30-50 av). Progressive, life-limiting, time-course 15-20 years,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.,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Huntington Disease,National protocol for pre-symptomatic testing blood test on minimum of session three, results at session four We see at-risk family members, along with affected patients with a new diagnosis Support from other sources: HDA Dr Vianithranian Consultant neurologists in Derby Helen James, HDA Family liaison worker,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,Mr P has been diagnosed with long QT syndrome (a heart condition which can result in sudden death). This is a dominant condition, so his 4 children (aged from 10-19 years) are all at 50% risk. Testing is advised in childhood, as there are health and screening implications for affected family members. Mr P tells you in confidence that one of his children is adopted (and therefore not at genetic risk) but does not know this. How might we proceed?,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,A similar situation,Cystic fibrosis,A couple have a newborn child who is diagnosed with cystic fibrosis. As a routine next step, we counsel them about having carrier testing to confirm their carrier statuses, as this allows testing in future pregnancies and allows carrier testing for the wider family. The wife calls after the clinic to confess that she is uncertain whether her husband is the father of her baby, and does not want us to test him, for fear of disclosure.,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 boys 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.,Supporting Genetics Education for Health www.geneticseducation.nhs.uk,A consanguineous couple attend the genetics clinic as they have a 7 year old son affected by Duchenne Muscular Dystrophy (DMD). Mum had genetic testing and is not a DMD carrier. The risk to future children is around 5% (due to the risk of gonadal mosaicism). They are now pregnant again and request prenatal testing. Fetal sexing was first offered and shows the baby to be female. Female carriers of DMD are healthy, and do not have muscle problems. This couple still request a CVS (with an associated 1% risk of miscarriage) to determine if the baby is a carrier. They say they will end the p