Presentation on theme: "Genetics in Primary Care"— Presentation transcript:
1 Genetics in Primary Care Dr. Jude HaywardGPwSI in Genetics, Bradford
2 The Genetics Explosion 30 articles in the BMJ in the last 3 months65 articles in the Guardian in the last 3 monthsRange of issues:Genes for common diseases e.g. ‘The Fat Gene’PIGDGM cropsForensic DNA databaseHFEA bill – human / animal hybrids
3 The Daily Telegraph Genetic breakthrough hails new cancer research era From The TimesSeptember 7, 2009Genetic breakthrough brings cure for Alzheimer’s a step closer December 16th 2009Genetic breakthrough hails new cancer research eraBy Richard Alleyne, Science CorrespondentThe genetic code of two of the most deadly cancers has been cracked by British scientists in a world first that opens up a whole new era in the treatment for the disease.(Science Photo Library)Inflammation seen in the brains of Alzheimer's sufferers was thought to be a secondary effect of the disease. The new findings suggest that it might actually be a primary causeDavid Rose, Health CorrespondentSupporting Genetics Education for Health
4 What does Genetics mean to you? TrickyDryHighly Specialised – sometimes the patients know more than you doInteresting challengeHard to explain to patients
5 What does ‘genetics’ mean to you? Craniofaciocutaneous SyndromeMental retardationASD / HOCMIcthyosisSparse HairHigh ForeheadProminent earsDepressed nasal bridge
7 Family History – why do we do it? Think of the patient you most recently asked for a family history – what was the situation / presenting problem?What did you do with that information?
8 Family History – why do we do it? To aid with accurate risk assessment - likelihood of developing a certain diseaseTo identify those who have an underlying genetic condition who would benefit from further information and servicesTo identify other members of the family who may be at riskThis leads to appropriate management strategies
9 Objectives for today’s session To outline the scope of genetics in primary careTo identify some useful guidelines and resources for cliniciansTo identify useful resources for patientsTo outline the structure of services providing care to patients with genetic issuesTo touch on common forms of inheritanceTo discuss some common presentations of patients with genetic issuesTo encourage ‘thinking Genetics’ where you might not have done before!
10 Scope of Genetics in Primary Care 10% of consultations have genetic aspectMostly multifactorial disease with genetic component e.g. CHD, asthma, Alzheimers, diabetesSingle gene disorders e.g. CF, Huntingdon’s,(Pharmacogenetics)Reproductive issues e.g. Hbopathies
11 Multifactorial Inheritance Increased risk due Geneticto family history ConditionEnvironmental factors Genetic Factors‘nurture’ ‘nature’
12 Role of Primary Health Care Team (RCGP) General Practitioners have a key role in identifying patients and families who would benefit from being referred to appropriate specialist genetic servicesManagement and support of families with / at risk of genetic conditionsConsideration of FH in multi-factorial disease e.g. cancer, DM, CHD
14 A ‘typical’ morning surgery… Mrs. B, aged 52, attends for a blood pressure check as she has had 2 raised readings over the last few months.Today it is 152 / 96. She says she’s not surprised it is raised as she has just heard that her sister has been diagnosed with ovarian cancer – this has come as a shock as she has been supporting her other sister through a course of chemotherapy for breast cancer.What else would you ask?
15 Of the general population will develop cancer during their lifetime Cancer is common1 in 3-4Of the general population will develop cancer during their lifetimeBreast cancer: 1 in 9 womenOvarian cancer: 1 in 35 womenBowel cancer: 1 in 18 men, 1 in 20 womenIncidence increases with age (risk factor)
16 Multifactorial Inheritance Increased risk due Geneticto family history ConditionEnvironmental factors Genetic Factors‘nurture’ ‘nature’
17 Recognising Hereditary/Familial Ca Younger age at diagnosis of cancerMultiple family members affectedSame cancersBilateral, or multiple primariesRelated cancers.... (unusual cancers)
18 Hereditary Cancer1 in 20 cases of breast, ovarian, CRC cancer are hereditary.Breast/ovarian cancer syndromes: BRCA 1 + 2Ass. cancers: Male Breast Cancer, Prostate Cancer, Certain melanomas, association with CML / renal cell carcinomaColorectal cancer syndromes: FAP / HNPCCHNPCC associated cancers: ovarian, endometrial, gastric, biliary, urinary tract
20 Risk assessment40-50 patients age per 2000 patients in GP have 1 first degree relative with CR, breast, ovarian or uterine cancer (UK)Familial Cancer: Primary Care Management of patients at risk of breast, ovarian or colorectal cancerBased on NICE and BSG guidelinesOPERA – tool for patients via MacMillan website
22 Useful information to include in referral: Name , DOB, address, NHS number, (telephone number)Whatever family history availableName(s) of affected family members if seen by any genetics team(Pregnant or non-pregnant)
23 Genetic ServicesYorkshire Regional Genetic Service (based at LGI: switchboard )Medical Staff: Consultants, RegistrarsGenetic CounsellorsFamily History AdministratorsDNA / Cytology labsOther specialties: Paediatrics, MidwivesOther services:Haemoglobinopathy and Sickle Cell ServiceGPwSI in Genetics
24 What happens when a referral is made? Referral received (can be via secondary care)Questionnaire sent out by family history administrators and returned by ptConsultants review referral and FHTriage to Genetic Counsellor / ConsultantOften initial contact with Genetic Counsellor
25 Genetic Counselling (Peter Rose) Information gathering:Discuss family historyIdentify patient concerns / wishesInformation provision:Explain risks and genetic contributionDiscuss screening if appropriatePreventative measuresDiscuss tests if appropriateDecision making:Guide patient through difficult choicesInstitute management which patient chooses
26 Genetic Counselling IS NON-DIRECTIVE Doesn’t always result in a test! ‘Genetic Counselling is the process by which patients or relatives at risk of a disorder which may be hereditary are advised of the consequences of the disorder, the probability of developing or transmitting it and the ways in which this may be prevented or avoided’
27 Familial / hereditary cancer Family History is used to assess riskPopulation risk:should be reassured and managed in Primary CareModerate / high risk (i.e. above population risk):Additional screening (mammogram +/- MRI)Risk-reducing surgery i.e. prophylactic mastectomy / oophorectomyHigh risk:may be offered testing for a particular syndrome
28 ‘Typical’ patient no. 1 – Mrs. B Could / Should be offered referral to GeneticsHigh risk for breast and ovarian cancerOffered screening:Yearly Mammogram +/- MRI from 35-5018 monthly mammogram from 50 onwardsOvarian screening via research studyOffered risk-reducing measures:Prophylactic Bilateral MastectomyProphylactic Bilateral OophorectomyOffered testing:Given information and testing discussed
29 A ‘typical’ morning surgery… Mrs T. attends, and after telling you about her athlete’s foot she bursts into tears and tells you her mother has just been diagnosed with cancer – ‘everyone in the family has it and I’m bound to get it’What else do you ask?She tells you:Mother had breast cancer aged 64Sister had cervical cancer in her 30’sHer grandfather had prostate cancer and died in his 80’sHer uncle developed lung cancer in his 60’s – he had been a heavy smoker all his life
30 Role of Primary Care (NICE 2006) Women at or near population risk should be cared for in Primary CareThey should receive standard information (see box in PACE Guidelines)‘Be Breast Aware’ (NHS Breast Screening Programme and Cancer Research UK)‘Are you worried about Breast Cancer?’ (Cancer Backup)
31 Communication…How would you try to reassure her that she wasn’t at any greater risk than the rest of the population?
35 Other resources for patients Can access via macmillan website
36 The story so far…Our job is to identify the 1 in 20 patients with cancer (and their relatives) with a genetic basisPACE guidelines can helpOnly some patients will be offered a genetic test – management is mainly information giving, extra screening, risk-reducing surgery.
38 When to think about it:A 34-year-old lady with a history of depression comes to see you. Her sister died very suddenly 2 weeks ago at the age of 42.She also happens to be your patient, and when you look in her notes, the cause of death from PM is Myocardial Infarction
39 Familial Hypercholesterolaemia 1 in 500 people have Familial Hypercholesterolaemia50% CVD risk by the age of 50 in men30% CVD risk by the age of 60 in women110,000 cases in the U.K.Only around 10,000 identified so far
40 Familial Hypercholesterolaemia Hot Topic at present…NICE guidelines:Familial Hypercholesterolaemia(August 2008)
41 When to think about it: Simon Broome Diagnostic Criteria TC >7.5, LDL >4.9 ANDDefinite FH:Tendon xanthomas in 1st or 2nd degree relativePossible FH:Family history of IHD <60 y.o.a. in 1st degree relative, and <50 y.o.a. in 2nd degree relativeFamily history of TC >7.5 in 1st or 2nd degree relative
44 How to manage it: Manage other risk factors Aggressively control cholesterol to lower LDL <50% level at initial measurementIf not controlled with 2 agents, refer:Donald Whitelaw (Diabetes and Endocrinology Consultant, BRI)Julian Barth / Mike Mansfield (Lipid clinic, LGI)Consider referral to cardiologist for assessment of possible IHD
45 What about the Genetics? Autosomal Dominantly InheritedMutation in LDL receptor geneIndividuals should be referred for genotyping.
46 What about the rest of the family? ‘Cascade Screening’ of all 1st and 2nd degree relatives – several pilot projects underway to figure out how to do this.Controversies:How do you assess for possible IHD?Children should be started on a statin as early as possible, around the age of 10
47 The story so far…If someone has a family history of premature heart diseaseor presents with a cholesterol over 7.5:Think Familial Hypercholesterolaemia
48 Other inherited cardiac conditions Specialist clinic at LGIFH of sudden cardiac deathFH of arrythmia, cardiomyopathy or connective tissue diseaseCan refer directlyAny queries: Kath Ashcroftor mobile
50 A ‘typical’ morning surgery… A 36-year-old man comes in ‘tired all the time’. He has several non-specific symptoms including palpitations and general aches, and you are aware he is having a stressful time at work.He is concerned, and asks you to do some blood tests.
51 Hereditary haemochromatosis High index of suspicion in younger men who present TATT.Autosomal recessive disorders, carrier rate 1/8 – 1/10, prevalence 1/200 – 1/400.Signs, Symptoms and Complications:Non-specific – tatt, joint pain, weight loss, (impotence)Liver diseaseDiabetesHypogonadotrophic hypognadismArthritisCardiac Disease (heart failure)Venesection improves life expectancy - normal if before development of diabetes and liver cirrhosis
52 Hereditary haemochromatosis His ferritin came back as What would you do next?Diagnosis:Ferritin: will be raised once iron overload occurring. Can also be raised in acute phase responseIf ferritin high, or high index of suspicion consider checking Fasting Transferrin (earliest marker of HH)If transferrin > 45%, refer to haematologistGenerally, females >50%, males >55%
53 Hereditary Haemochromatosis Genetics:2 mutations responsible for >95% in U.K.Many people who inherit the mutations will not develop clinical disease.Genetics dept will offer gene testing / genotyping to 1st degree relatives only.
54 Other examples!A 24-year-old man who is diagnosed with Type 2 Diabetes. He has a normal BMI, is caucasian, and has no family history.A 59-year-old man who is caring for his wife who has just been diagnosed at 57 with early onset Alzheimer’s. Her mother also had dementia of some sort.
56 Recessive Inheritance ParentsCarrierSperm & eggsWith all recessive conditions, the child can only be affected if both parents are carriers. However, rarely new mutations can and do occurThe slide is sequenced, at each level explain:Both parents are carriers: they each have one altered and one usual copy of the gene instead of two usual copies. Carriers are usually healthyEach sperm and egg cell (gamete) has a 50% chance of containing the altered copy of the gene, or a 50% chance of containing the usual geneIf both parents are carriers, AT CONCEPTION each child has a 25% (1 in 4) risk of being affected with the condition and a 50% (1 in 2) chance of being a carrierOffspringNormalCarrierCarrierAffected
57 Autosomal Recessive Inheritance Affects one generationBoth sexes affectedMale – male transmission
58 Resources for patients Support for families in which there is a rare genetic disorder
59 This is the slide to remember! Our role is identify patients at risk or who may have a genetic condition and would benefit from input from Genetic ServicesWe do this by taking and using a family history – core examples:A common multifactorial disease (e.g. IHD or cancer) occurring young, strong family history, atypical presentationEarly pregnancy, or even pre-conceptuallyThere is lots of information out there regarding individual conditions
61 Supporting Genetics Education for Health An on-line resource to support the genetics curriculum statement is the ‘genetics in primary care module’ of the eGP project.Supporting Genetics Education for Health61
62 Resources: Me! firstname.lastname@example.org YGS via LGI switchboard:‘Recognising the common patterns of inheritance in families’(apogi sheets
64 Pedigree Symbols / Male Marriage / Partnership (horizontal line) Female/Partnership that has endedPerson whose sex is unknownPOffspring (vertical line)PregnancyX weeksMiscarriageParents and SiblingsAffected Male & FemaleCarrier Male & FemaleSupporting Genetics Education for HealthSupporting Genetics Education for Health
65 Supporting Genetics Education for Health Family HistoryJane (28) is 6 weeks pregnantJane’s husband Christopher (29) is an only childHis parents William (60) and Margaret (59) are alive and wellJane has one brother John (34), he had one son David (10) to his first wife Alice (33). Their marriage ended in divorceJohn’s second wife Christine (29) had a miscarriage at 9 weeks and a son Richard (4) who has CFJane’s father George Whitehead died at the age of 66Jane’s mother Joan (64) is alive and wellSupporting Genetics Education for Health
66 Supporting Genetics Education for Health JoanMargaretWilliam HobsonGeorge WhiteheadJoan6059Died age 6664Christopher HobsonJaneAliceJohn WhiteheadChristine2928333429P9 weeks6 weeksDavidRichard104Assume 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? (Population risk of being CF carrier for people with North European ancestry = 1 in 25)Cystic fibrosisSupporting Genetics Education for Health
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