genetics in primary care dr. jude hayward gpwsi in genetics, bradford
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Genetics in Primary Care
Dr. Jude Hayward
GPwSI in Genetics, Bradford
The Genetics Explosion
30 articles in the BMJ in the last 3 months 65 articles in the Guardian in the last 3 months Range of issues:
Genes for common diseases e.g. ‘The Fat Gene’ PIGD GM crops Forensic DNA database HFEA bill – human / animal hybrids
Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk
From The TimesSeptember 7, 2009
Genetic breakthrough brings cure for Alzheimer’s a step closer
(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 Correspondent
Genetic breakthrough hails new
cancer research era
By Richard Alleyne, Science Correspondent
The 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.
December 16th 2009
The Daily Telegraph
What does Genetics mean to you?
Tricky Dry Highly Specialised – sometimes the
patients know more than you do Interesting challenge Hard to explain to patients
What does ‘genetics’ mean to you?
Craniofaciocutaneous Syndrome
Mental retardationASD / HOCM
IcthyosisSparse Hair
High ForeheadProminent ears
Depressed nasal bridge
What would you like to know?
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?
Family History – why do we do it?
To aid with accurate risk assessment - likelihood of developing a certain disease
To identify those who have an underlying genetic condition who would benefit from further information and services
To identify other members of the family who may be at risk
This leads to appropriate management strategies
Objectives for today’s session
To outline the scope of genetics in primary care To identify some useful guidelines and resources for
clinicians To identify useful resources for patients To outline the structure of services providing care to
patients with genetic issues To touch on common forms of inheritance To discuss some common presentations of patients with
genetic issues To encourage ‘thinking Genetics’ where you might not
have done before!
Scope of Genetics in Primary Care
10% of consultations have genetic aspect Mostly multifactorial disease with genetic
component e.g. CHD, asthma, Alzheimers, diabetes
Single gene disorders e.g. CF, Huntingdon’s, (Pharmacogenetics) Reproductive issues e.g. Hbopathies
Multifactorial Inheritance
Increased risk due Genetic to family history Condition
Environmental factors Genetic Factors‘nurture’ ‘nature’
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 services
Management and support of families with / at risk of genetic conditions
Consideration of FH in multi-factorial disease e.g. cancer, DM, CHD
A typical morning surgery…
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?
Cancer is common
1 in 3-4Of the general population will develop cancer
during their lifetime
Breast cancer: 1 in 9 women Ovarian cancer: 1 in 35 women Bowel cancer: 1 in 18 men, 1 in 20 women Incidence increases with age (risk factor)
Multifactorial Inheritance
Increased risk due Genetic to family history Condition
Environmental factors Genetic Factors‘nurture’ ‘nature’
Recognising Hereditary/Familial Ca
Younger age at diagnosis of cancer Multiple family members affected Same cancers Bilateral, or multiple primaries Related cancers.... (unusual cancers)
Hereditary Cancer
1 in 20 cases of breast, ovarian, CRC cancer are hereditary.
Breast/ovarian cancer syndromes: BRCA 1 + 2 Ass. cancers: Male Breast Cancer, Prostate Cancer, Certain
melanomas, association with CML / renal cell carcinoma
Colorectal cancer syndromes: FAP / HNPCC HNPCC associated cancers: ovarian, endometrial, gastric,
biliary, urinary tract
Autosomal Dominant Inheritance
Risk assessment
40-50 patients age 35-64 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 cancer
www.learnonline.nhs.uk Based on NICE and BSG guidelines
OPERA – tool for patients via MacMillan website
Useful information to include in referral: Name , DOB, address, NHS number,
(telephone number) Whatever family history available Name(s) of affected family members if
seen by any genetics team (Pregnant or non-pregnant)
Genetic Services
Yorkshire Regional Genetic Service (based at LGI: switchboard 0113 243 2799)
Medical Staff: Consultants, Registrars Genetic Counsellors Family History Administrators DNA / Cytology labs
Other specialties: Paediatrics, Midwives Other services:
Haemoglobinopathy and Sickle Cell Service GPwSI in Genetics
What happens when a referral is made? Referral received (can be via secondary care) Questionnaire sent out by family history
administrators and returned by pt Consultants review referral and FH Triage to Genetic Counsellor / Consultant Often initial contact with Genetic Counsellor
Genetic Counselling (Peter Rose)
Information gathering: Discuss family history Identify patient concerns / wishes
Information provision: Explain risks and genetic contribution Discuss screening if appropriate Preventative measures Discuss tests if appropriate
Decision making: Guide patient through difficult choices Institute management which patient chooses
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’
Familial / hereditary cancer
Family History is used to assess risk Population risk:
should be reassured and managed in Primary Care Moderate / high risk (i.e. above population risk):
Additional screening (mammogram +/- MRI) Risk-reducing surgery i.e. prophylactic mastectomy /
oophorectomy High risk:
may be offered testing for a particular syndrome
‘Typical’ patient no. 1 – Mrs. B
Could / Should be offered referral to Genetics High risk for breast and ovarian cancer Offered screening:
Yearly Mammogram +/- MRI from 35-50 18 monthly mammogram from 50 onwards Ovarian screening via research study
Offered risk-reducing measures: Prophylactic Bilateral Mastectomy Prophylactic Bilateral Oophorectomy
Offered testing: Given information and testing discussed
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 64 Sister had cervical cancer in her 30’s Her grandfather had prostate cancer and died in his 80’s Her uncle developed lung cancer in his 60’s – he had been a
heavy smoker all his life
Role of Primary Care (NICE 2006)
Women at or near population risk should be cared for in Primary Care
They 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)
Communication…
How would you try to reassure her that she wasn’t at any greater risk than the rest of
the population?
Aled
Maud
CRC@58
Sian
CRC@57
Aled
37
Olwen
34
Huw
CRC@54
Dai
34
Wynn
33
Browyn
50
Tom
29
John
Died young?renal Ca
MargaretRenal Ca@42
RoyRenal Ca@50
Pat58
Jenny40
John38
Richard35
Mark33
Judith30 28
Jane20
Julian18
Becky16
Lily13
Other resources for patients
www.cancerbackup.org.uk 0808 800 1234 www.cctrust.org.uk 020 7704 1137 http://www.macmillan.org.uk/Get_Support/
Cancer_types/Genetic_risk_factors.aspx Can access via macmillan website
The story so far…
Our job is to identify the 1 in 20 patients with cancer (and their relatives) with a genetic basis
PACE guidelines can help Only some patients will be offered a
genetic test – management is mainly information giving, extra screening, risk-reducing surgery.
A typical morning surgery…
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
Familial Hypercholesterolaemia
1 in 500 people have Familial Hypercholesterolaemia
50% CVD risk by the age of 50 in men 30% CVD risk by the age of 60 in women 110,000 cases in the U.K. Only around 10,000 identified so far
Hot Topic at present…
NICE guidelines:
Familial Hypercholesterolaemia
(August 2008)
When to think about it: Simon Broome Diagnostic Criteria TC >7.5, LDL >4.9 AND Definite FH:
Tendon xanthomas in 1st or 2nd degree relative
Possible FH: Family history of IHD <60 y.o.a. in 1st degree relative,
and <50 y.o.a. in 2nd degree relative Family history of TC >7.5 in 1st or 2nd degree relative
Fig. Disease box 11 ©Scion
Publishing LtdPhotos courtesy of Dr Paul Durrington.
Cholesterol deposition in patients heterozygous for familial hypercholesterolemia. (a, b) Tendon xanthomata, and (c) corneal arcus.
DO NOT USE THESE!
How to manage it:
Manage other risk factors Aggressively control cholesterol to lower LDL
<50% level at initial measurement If 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
What about the Genetics?
Autosomal Dominantly Inherited Mutation in LDL receptor gene Individuals should be referred for
genotyping.
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
The story so far…
If someone has a family history of premature heart disease
or presents with a cholesterol over 7.5:
Think Familial Hypercholesterolaemia
Other inherited cardiac conditions
Specialist clinic at LGI FH of sudden cardiac death FH of arrythmia, cardiomyopathy or
connective tissue disease Can refer directly Any queries: Kath Ashcroft
0113 3925784 or mobile 07789003997
A typical morning surgery…
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.
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 disease Diabetes Hypogonadotrophic hypognadism Arthritis Cardiac Disease (heart failure)
Venesection improves life expectancy - normal if before development of diabetes and liver cirrhosis
Hereditary haemochromatosis
His ferritin came back as 458. What would you do next?
Diagnosis: Ferritin: will be raised once iron overload occurring.
Can also be raised in acute phase response If ferritin high, or high index of suspicion consider
checking Fasting Transferrin (earliest marker of HH) If transferrin > 45%, refer to haematologist Generally, females >50%, males >55%
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.
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.
A typical morning surgery…
Offspring
Sperm & eggs
AffectedCarrier
Parents
CarrierCarrier
CarrierNormal
Recessive Inheritance
Autosomal Recessive Inheritance
– Affects one generation– Both sexes affected– Male – male
transmission
Resources for patients
www.cafamily.org.ukSupport for families in which there is a rare
genetic disorder
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 Services
We 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 presentation Early pregnancy, or even pre-conceptually
There is lots of information out there regarding individual conditions
Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk
Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk
Resources:
Me! judith.hayward@bradford.nhs.uk YGS via LGI switchboard: 0113 243 2799 www.gpnotebook.com www.geneticseducation.nhs.uk ‘Recognising the common patterns of
inheritance in families’ www.library.nhs.uk/genepool www.chime.ucl.ac.uk (apogi sheets
Thank you!
Any questions?
Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk
Male
Female
Person whose sex is unknown
PregnancyP
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
Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk
Family History Jane (28) 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 Jane’s mother Joan (64) is alive and well
Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk
Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk
JoanMargaret
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? (Population risk of being CF carrier for people with North European ancestry = 1 in 25)
George WhiteheadDied age 66
Joan64
John Whitehead34
Jane28
Christine 29
Richard4
Cystic fibrosis
9 weeks
Christopher Hobson29
William Hobson60 59
P
6 weeks
Alice33
David10
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