1、Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukPractical Genetics for Primary Care6th February 2013Marie-Anne OReillyGenetic Counsellor Nottingham Clinical Genetics ServiceEmail:Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukOverview Introduction to genetics
2、 for GPs Taking a family history Family cancer genetics Making a referral to the genetic department Sources of further information Ethical dilemmasSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukWhen might a GP see genetics in practice?Clinical managementCommunicating genetic inf
3、ormationIdentifying patientsSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukChromosomal disordersSyndromes:Down,Turner,Klinefelter.Chromosomal TranslocationsAutosomal dominant disordersAdult polycystic kidney diseaseNeurofibromatosisHuntington DiseaseHypercholesterolemiaMarfan Sy
4、ndromeFamilial CancerBowel/Uterine/Ovarian?LynchBreast/Ovarian/Prostate?BRCA1/2Autosomal recessive disordersCystic FibrosisHaemoglobinopathiesHaemochromatosisX-Linked disordersDuchenne and Becker MusculardystrophiesHaemophilia AFragile XVariable inheritance patternsDeafnessMuscular dystrophiesCommon
5、/important conditionsSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukOther 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 Geneti
6、cs Education for Healthwww.geneticseducation.nhs.ukQuestions 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 Healthwww
7、.geneticseducation.nhs.ukWhy is the patient asking their question now?Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukWhy 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
8、?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 Healthwww.geneticseducation.nhs.ukGenetic family history1.Why is family history information important t
9、o 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 pedigrees3.How do I interpret family history information?Factsheets and slides on Understanding Modes of Inheritance Fa
10、ctsheets and worksheets on Interpreting a Family HistorySupporting Genetics Education for Healthwww.geneticseducation.nhs.ukMaleFemalePerson whose sex is unknownPregnancyPMarriage/Partnership(horizontal line)Parents and SiblingsOffspring(vertical line)Affected Male&FemaleCarrier Male&FemalePartnersh
11、ip that has endedPedigree Symbols/X weeksMiscarriageSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukSBUnaffected person,sex unknownTwins:identical;non-identicalDouble line showsconsanguineous coupleStillborn baby,unknown sexTherapeuticabortionAffected male Unaffected female who h
12、as diedAffected female Spontaneous abortionSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukIs my baby at risk of cystic fibrosis?Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukScenario Watch a video of a GP being consulted by Jane Hobson.She is in the early s
13、tages 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 d
14、raw out the pedigree as it is being taken.Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukCF video family history clipSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukGeorgeDied age 65,2007Joan63John Whitehead27Jane29Christine 30RichardBorn 2004Cystic fibrosis9
15、 weeksChristopher Hobson29William60Joan63P6 weeksJulie27David10Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukFrom the family pattern,who must be carriers for cystic fibrosis?George WhiteheadDied age 65,2007Joan63John Whitehead27Jane29Christine 30RichardBorn 2004Cystic fibrosis9
16、 weeksChristopher Hobson29William60Joan63P6 weeksJulie27David10Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukIs the probability of Jane Hobson being a carrier for cystic fibrosis sufficiently high to offer testing?orGeorgeDied age 65,2007Joan63John Whitehead27Jane29Christine 30
17、RichardBorn 2004Cystic fibrosis9 weeksChristopher Hobson29William60Joan63P6 weeksJulie27David10Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukAssume Jane was tested and found to be a carrier.What is the probability that the baby in Jane and Christopher Hobsons current pregnancy
18、will have cystic fibrosis?GeorgeDied age 65,2007Joan63John Whitehead27Jane29Christine 30RichardBorn 2004Cystic fibrosis9 weeksChristopher Hobson29William 60Joan63P6 weeksJulie27David10Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukAt what stage should specialist genetic advice b
19、e sought?GeorgeDied age 65,2007Joan63John Whitehead27Jane29Christine 30RichardBorn 2004Cystic fibrosis9 weeksChristopher Hobson29William 60Joan63P6 weeksJulie27David10Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukNow!-Need to identify familial mutations-Need to test partner to
20、clarify risksSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukGeorgeDied age 65,2007Joan63John Whitehead27Jane29Christine 30RichardBorn 2004Cystic fibrosis9 weeksChristopher Hobson29William 60Joan63P6 weeksJulie27David10N/NN/dF508N/dF508dF508/dF508Supporting Genetics Education for
21、 Healthwww.geneticseducation.nhs.ukPre-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 diagnosisFet
22、al sexing on blood for X-linked conditionsPGD 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
23、 for Healthwww.geneticseducation.nhs.ukFamilial Cancer Genetics Inheritance patterns When to make a referral Who to refer to Sources of information and adviceSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukDominant breast cancer genes BRCA1 and BRCA2 identified and clinical testi
24、ng 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 cancersParentsGametesAt conceptionAutosomal Dominant InheritanceAffectedUnaffectedCancerHereditarygene change1 Somatic mutat
25、ionNormal TissueSomatic mutationCancerHereditarygene changeSomatic mutationCancer2 Somatic mutationsSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukAssessing risk where there is a history of cancerCasesSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukWhat facto
26、rs do you think may indicate a woman is at higher risk of breast/ovarian cancer?Case 155Breast cancer46Kay6576495153 70Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukCase 155Breast cancer46Kay6576495153 70Low risk manage in primary careOlder age of onsetDifferent sides of the fa
27、milyReassure and explain population risk,advise on symptom awareness and to report any changes in family historyCase 232JanetBreast cancerOvarian cancer3548 breast cancer 56 ovarian cancer42Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukCase 232JanetBreast cancerOvarian cancerRe
28、fer high riskDifferent generationsYoung age onsetEqual transmission through menMultiple tumours in one individualBreast and ovarian cancer3548 breast cancer 56 ovarian cancer42Refer to Wendy Chorley(familial cancer service)Royal Derby Hospital.They will offer a referral to genetics where indicated.S
29、upporting Genetics Education for Healthwww.geneticseducation.nhs.ukFamilial 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
30、 cancer(HNPCC)Most dominant not all!Case 37352Peter7560s78736377 35 died in war68Colorectal cancerSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukCase 37352Peter7560s78736377 35 died in war68Colorectal cancerLow risk reassure-advise on symptom awareness and reporting.FOB testing
31、from 60y.Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukCase 47340Peter7560s78734377 35 died in war68Colorectal cancerSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukCase 47340Peter7560s78734377 35 died in war68Colorectal cancerRefer moderate riskYoung age of
32、 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 5Colorectal cancerEndometrial cancer80756955784842George494230Martin39Polyps Supporting Genetics Education for Healthwww.
33、geneticseducation.nhs.ukCase 5Colorectal cancerEndometrial cancer80756955784842George494230Martin39Polyps Refer high riskYoung age of onsetEndometrial and bowel cancers(other related cancers include ovarian,ureteric,renal pelvis,gastric)Two generationsPolyps Refer to Wendy Chorley-diagnoses would be
34、 confirmed,offer genetic testing to George.Bowel screening would be offered to at-risk family members.Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukAssessing cancer risk Young age of onset,pattern of similar tumours in a family(or multiple primaries in one person)Related tumour
35、s 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 Healthwww.geneticseducation.nhs.ukCance
36、r 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 initiallySupporting Genetics Education fo
37、r Healthwww.geneticseducation.nhs.ukMaking 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 telephon
38、e number home and daytime contact(check mobile!)Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukMaking 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 patien
39、t is in the last stages of a terminal illnessSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukSources of information Local or national guidelines e.g NICE Discussing with a colleague Contact the local CGS InternetSupporting Genetics Education for Healthwww.geneticseducation.nhs.uk
40、National Genetics Education and Development CentreSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukOther things we do Provide open access for que
41、stions(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 Healthwww.geneticseducation.nhs.ukTo refer or not refer?Please call Nottingham Reg
42、ional 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 Healthwww.geneticseducation.nhs.ukReferral AddressNottingham Clinical G
43、enetics Service,City Hospital Campus,The Gables,Gate 3,Hucknall RoadNottinghamNG5 1PBTel:0115 962 7728Fax:0115 962 8042Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukConfidentiality:Ethical Issues in Primary Care GeneticsSupporting Genetics Education for Healthwww.geneticseducat
44、ion.nhs.ukHuntington 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 yearsSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukJane is a healthy,24 year o
45、ld 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,t
46、o 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 de
47、velop HD.Jane should not be offered genetic testing without first testing her mother.Strongly agreeAgreeNeutralDisagreeStrongly disagree Supporting Genetics Education for Healthwww.geneticseducation.nhs.ukHuntington Disease National protocol for pre-symptomatic testing blood test on minimum of sessi
48、on 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 workerSupporting Genetics Education for Healthwww.geneticseducation.nhs.ukM
49、r 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 tel
50、ls 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 Healthwww.geneticseducation.nhs.ukA similar situationCystic fibrosisA couple have a newborn child who is diagnosed with cystic fibr
