Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk
Practical Genetics for Primary Care
6th February 2013
Kate Carter
Genetic Counsellor
Nottingham Clinical Genetics Service
Telephone: 0115 962 7728
Email: [email protected]
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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
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When might a GP see genetics in
practice?
Clinical management
Communicating genetic information
Identifying patients
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Chromosomal disordersSyndromes: Down, Turner,Klinefelter. Chromosomal Translocations
Autosomal dominant disordersAdult polycystic kidney diseaseNeurofibromatosisHuntington DiseaseHypercholesterolemiaMarfan Syndrome
Familial CancerBowel/Uterine/Ovarian ?HNPCCBreast/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
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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?
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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?
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Is my baby at risk of cystic fibrosis?
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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.
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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
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CF video family history clip
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George
Died age 65, 2007
Joan63
John Whitehead27
Jane29
Christine 30
RichardBorn 2004
Cystic fibrosis
9 weeks
Christopher Hobson29
William60
Joan63
P
6 weeks
Julie27
David10
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From the family pattern, who must be carriers for cystic fibrosis?
George Whitehead
Died age 65, 2007
Joan63
John Whitehead27
Jane29
Christine 30
RichardBorn 2004
Cystic fibrosis
9 weeks
Christopher Hobson29
William60
Joan
63
P6 weeks
Julie27
David10
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Is the probability of Jane Hobson being a carrier for cystic fibrosis sufficiently high to offer testing?
or
George
Died age 65, 2007
Joan63
John Whitehead27
Jane29
Christine 30
RichardBorn 2004
Cystic fibrosis
9 weeks
Christopher Hobson29
William60
Joan63
P
6 weeks
Julie27
David10
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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
Joan63
John Whitehead27
Jane29
Christine 30
RichardBorn 2004
Cystic fibrosis
9 weeks
Christopher Hobson29
William 60
Joan63
P
6 weeks
Julie27
David10
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At what stage should specialist genetic advice be sought?
George
Died age 65, 2007
Joan63
John Whitehead27
Jane29
Christine 30
RichardBorn 2004
Cystic fibrosis
9 weeks
Christopher Hobson29
William 60
Joan63
P
6 weeks
Julie27
David10
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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’
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Familial Cancer Genetics
• When to make a referral
• Who to refer to
• Sources of information and advice
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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
Parents
Gametes
At conception
Autosomal Dominant Inheritance
AffectedUnaffected
Cancer
Hereditarygene change
1 Somatic mutation
Normal Tissue
Somatic mutation
Cancer
Hereditarygene change
Somatic mutation
Cancer
2 Somatic mutations
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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
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
32Janet
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.
Number of close relatives affected by breast cancer
Family History of breast cancer
Age of cancer diagnosis Refer to combined FH clinic
(Breast Unit)
≤ 40
> 40 X
(bilateral) < 50
(2nd primary can be over 50) 1 (first degree)
(male) Any age
2 (one 1st degree)
Average age under 60
3 (or more)
Any age
OVARIAN CANCER FAMILIES BREAST & OVARIAN CANCER FAMILIES Number of close relatives affected by ovarian cancer
Action Number of close relatives affected by either breast or
ovarian cancer Refer to FH clinic
1 No screening required
1 both breast and ovarian cancer
2 or more Refer to FH clinic
1 male breast cancer and 1 ovarian cancer Key
1 breast and 1 ovarian cancer (one 1st degree) Green is low risk No action
required
3 or more breast and/or ovarian cancer at any age Orange is moderate or high risk Refer to FH clinic
What to do if a patient has a family history of Breast/Ovarian Cancer
A close relative is any first or second degree relative (parent, brother, sister, child, aunt, uncle, grandparent). Please remember if there are intervening male relatives then more distant relationships maybe relevant.
The family history should be of affected blood relatives through either the maternal or paternal side of the family. If there is Jewish ancestry in the family, the history may be more significant – seek advice from the Clinical Genetics service. Refer affected patients and close female relatives. For enquiries about a patient’s family history you can contact the Cancer Family History Service tel: 01332 785771 or 788555
or the Clinical Genetics Service on : 0115 9627728
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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
32Peter
75
60s
78
73
4377
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
Case 4
Colorectal cancer
Endometrial cancer
80 75
6955
784842
George
49
4230Martin
39Polyps
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.
Key Green is low risk Orange is moderate risk Pink is moderate to high risk Red is high risk
Number of close relatives with bowel cancer
Age of cancer diagnosis Refer to FH clinic
1(1st degree) < 50
> 50 x
1 (1st degree) Separate or multiple tumours at any age
1 (1st degree-polyps only) More than one significant (>10mm) polyp under 50yrs Average age < 70
2 (same side or both parents) >70 x
2 (same side)* Average age <50
3 or more (same side)* Any age
Polyposis Coli Positive family history
*Related cancers: When there is, in addition to at least one bowel cancer, a history of endometrial, ovarian, gastric, biliary, renal, small bowel or brain cancer in other close relatives.
What to do if a patient has a family history of bowel and related cancers.
A close relative is any first or second degree relative (parent, brother, sister, child, aunt, uncle, grandparent). The family history should be of affected blood relatives through either the maternal or paternal side of the family. For enquiries about a patient’s family history contact the Cancer Family History Service tel: 01332 785771 or 788555 or the
Clinical Genetics Service on : 0115 9627728 ,
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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
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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
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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
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Sources of information
• Local or national guidelines e.g NICE
• Discussing with a colleague
• Contact the local CGS
• Internet
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National Genetics Education and Development Centre
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To refer or not refer?
• Please call Nottingham Regional Clinical
Genetics Service for advice and information
• Tel: 0115 962 7728
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Referral AddressNottingham Clinical Genetics Service,
City Hospital Campus,
The Gables, Gate 3,
Hucknall Road
Nottingham
NG5 1PB
Tel: 0115 962 7728
Fax: 0115 962 8042
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Ethical Issues in Primary Care Genetics
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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?
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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.
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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
Agree Neutral Disagree Strongly disagree
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Erica, 35
Eve, BRCA1
No knowledge
Strong family history of
breast / ovarian cancer (BRCA1)
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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
Agree Neutral Disagree Strongly disagree
Consider the statement above and indicate the extent to which you agree or disagree with it.
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A consanguineous couple attend the genetics clinic as they have a 7 year old son affected by Duchenne Muscular Dystrophy (DMD).
They are pregnant again and request prenatal testing.
Fetal sexing is 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 pregnancy if this child is a carrier.
What should you do?
Test Uncertain Not test
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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
Agree Neutral Disagree Strongly disagree
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Cystic fibrosis
Homozygous for very rare genetic change
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P
Cystic fibrosis
4 years
8 years
Jo Dan
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P
Cystic fibrosis
4 years
8 years
Dan: “variant of unknown significance”
Jo
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Thanks so much for your time!
Kate Carter
Genetic Counsellor
Nottingham Regional Clinical Genetics Service, Nottingham City Hospital
Telephone: 0115 9627728
Email: [email protected]