Transcript Genetics in Primary Care’

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?
Identifying
patients
Communicating
genetic information
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Clinical
management
Common / important conditions
Chromosomal disorders
Syndromes: Down, Turner,
Klinefelter.
Chromosomal Translocations
Autosomal recessive disorders
Cystic Fibrosis
Haemoglobinopathies
Haemochromatosis
Autosomal dominant disorders
Adult polycystic kidney disease
Neurofibromatosis
Huntington Disease
Hypercholesterolemia
Marfan Syndrome
X-Linked disorders
Duchenne and Becker Muscular
dystrophies
Haemophilia A
Fragile X
Familial Cancer
Bowel/Uterine/Ovarian ?HNPCC
Breast/Ovarian/Prostate ?BRCA1/2
Variable inheritance patterns
Deafness
Muscular dystrophies
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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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Pedigree Symbols
Male
Marriage / Partnership
(horizontal line)
Female
/
Partnership that has
ended
Person whose sex is
unknown
P
Offspring (vertical line)
Pregnancy
Miscarriage
X weeks
Affected Male & Female
Carrier Male & Female
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Parents and Siblings
CF video family history clip
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William
60
Joan
63
George
Joan
63
Died age 65, 2007
Christopher Hobson
29
Jane
29
Julie
27
John Whitehead
27
P
6 weeks
Christine
30
9 weeks
David
10
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Richard
Born 2004
Cystic fibrosis
William
60
Joan
63
Christopher Hobson
29
Joan
63
George Whitehead
Died age 65, 2007
Jane
29
Julie
27
John Whitehead
27
P
6 weeks
Christine
30
9 weeks
David
10
Richard
Born 2004
Cystic fibrosis
From the family pattern, who must be carriers for
cystic fibrosis?
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William
60
Joan
63
George
Joan
63
Died age 65, 2007
Christopher Hobson
29
Jane
29
Julie
27
John Whitehead
27
Christine
30
or
P
9 weeks
6 weeks
David
10
Richard
Born 2004
Cystic fibrosis
Is the probability of Jane Hobson being a carrier
for cystic fibrosis sufficiently high to offer testing?
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William
60
Joan
63
George
Joan
63
Died age 65, 2007
Christopher Hobson
29
Jane
29
Julie
27
John Whitehead
27
P
6 weeks
Christine
30
9 weeks
David
10
Richard
Born 2004
Cystic fibrosis
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?
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William
60
Joan
63
George
Joan
63
Died age 65, 2007
Christopher Hobson
29
Jane
29
Julie
27
John Whitehead
27
P
6 weeks
Christine
30
9 weeks
David
10
Richard
Born 2004
Cystic fibrosis
At what stage should specialist genetic advice be
sought?
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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
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Autosomal Dominant Inheritance
Parents
Gametes
At conception
Unaffected
Affected
Hereditary
gene change
Somatic
mutation
Cancer
1 Somatic
mutation
Normal
Tissue
Hereditary
gene change
Somatic
mutation
Cancer
2 Somatic
mutations
Cancer
What factors do you think may
indicate a woman is at higher
risk of breast / ovarian cancer?
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Low risk – manage in
primary care
Case 1
•Older age of onset
•Different sides of the
family
Breast
cancer
65
70
46
Kay
76
49
51
53
Reassure and explain population risk, advise on symptom
awareness and to report any changes in family history
55
Refer –high risk
•Different generations
Case 2
•Young age onset
•Equal transmission
through men
•Multiple tumours in one
individual
42
•Breast and ovarian
cancer
Breast cancer
Ovarian cancer
48 breast
cancer
56 ovarian
cancer
32
Janet
35
Refer – to Wendy Chorley (familial cancer service) – Royal Derby Hospital.
They will offer a referral to genetics where indicated.
What to do if a patient has a family history of Breast/Ovarian Cancer
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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
Number of close relatives
affected by breast cancer
Family History of breast
cancer
Refer to combined FH clinic
(Breast Unit)
Age of cancer diagnosis
≤ 40
1 (first degree)
(bilateral)
> 40
< 50
(2nd primary can be over 50)
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X

Any age

2 (one 1st degree)
Average age under 60

3 (or more)
Any age

(male)
OVARIAN CANCER FAMILIES
Number of close relatives
Action
affected by ovarian cancer
No screening
1
required
Refer to FH
2 or more
clinic
Key
Green is low risk
Orange is moderate or high risk
BREAST & OVARIAN CANCER FAMILIES
Number of close relatives affected by either breast or
Refer to
ovarian cancer
FH clinic
1
both breast and ovarian cancer
1
male breast cancer and 1
1
No action
required
Refer to FH clinic
breast and 1
3 or more
ovarian cancer
ovarian cancer (one 1st degree)
breast and/or ovarian cancer at any age
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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!
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Refer –moderate
risk
Case 3
•Young age of
onset (under 45)
73
35
died in war
60s
77
73
43
75
68
78
32
Colorectal cancer
Peter
Refer to Wendy Chorley Familial Cancer Service Royal Derby Hospital first degree relatives offered bowel screening. No genetic testing available
Refer –high risk
Case 4
•Young age of onset
•Endometrial and
bowel cancers (other
related cancers
include ovarian,
ureteric, renal pelvis,
gastric)
55
49
69
•Two generations
42
80
•Polyps
75
48
George
78
Endometrial cancer
Colorectal cancer
30
Martin
39
Polyps
42
Refer to Wendy Chorley - diagnoses would be confirmed, offer genetic
testing to George. Bowel screening would be offered to at-risk family
members.
What to do if a patient has a family history of bowel and related cancers.
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
1(1st degree)
1 (1st degree)
Age of cancer diagnosis
Refer to
FH clinic
< 50

> 50
x
Separate or multiple tumours at any age
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More than one significant (>10mm) polyp under 50yrs
2 (same side or both parents)
Average age < 70
>70
2 (same side)*
Average age <50
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x
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Any age
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Positive family history
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1 (1st degree-polyps only)
3 or more (same side)*
Polyposis Coli
*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.
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

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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
,
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 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
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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
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Strongly
disagree
Strong family
history of breast
/ ovarian cancer
(BRCA1)
Eve,
BRCA1
No knowledge
Erica,
35
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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.
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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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
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Not test
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
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Disagree Strongly
disagree
Cystic fibrosis
Homozygous for very
rare genetic change
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Jo
Dan
P
8 years
Cystic fibrosis
4 years
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Jo
Dan: “variant
of unknown
significance”
P
8 years
Cystic fibrosis
4 years
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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]
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