Transcript Genetics in Primary Care’

Genetics for GPR’s
Thank you for inviting me…
Susan Fairgrieve
Principal Genetic Counsellor
Aims
1. Highlight the relevance of genetics to your
practice
2. Review skills in taking and interpreting
family histories (discussing cases)
3. Making a referral
Recognition from RCGP
Identifying
patients
Communicating
genetic information
Clinical
management
What do you encounter?
Have you made a referral to Genetics?
Do patients ask about either passing on or
developing an illness that ‘runs in the family’?
What proportion of the UK population will
develop a genetic condition ?
1 in 20 before the age of 25, 60% in later life
have conditions with a genetic component
On average - how many consultations
relating to family cancer do GPs have
every year?
Common / Important Conditions
Chromosomal disorders
Syndromes: Down’s, Edward’s,
Patau’s, Turner’s, Klinefelter’s.
Chromosomal Translocations
Autosomal recessive disorders
Cystic Fibrosis
Haemoglobinopathies
Haemochromatosis
Autosomal dominant disorders
Familial Hypercholesterolemia
Huntington’s Disease
Marfan’s Syndrome
Neurofibromatosis
X-Linked disorders
Duchenne Muscular Dystrophy
Haemophilia A
Fragile X syndrome
Familial Cancer
Variable inheritance patterns
Bowel/Uterine/Ovarian ?HNPCC
Deafness
Breast/Ovarian/Prostate ?BRCA1/2
Common Reasons for Referrals
• Strong family history of breast/ovarian or bowel
cancer (predictive genetic testing may sometimes
be available)
• Investigation, diagnosis and ongoing support for
people with a genetic condition in the family
– family history (e.g. Huntington’s Disease)
– sporadic event (e.g. child with developmental delay)
• Cascade testing where there is a known family
history of a condition
• Genetic counselling for prenatal diagnosis
The Appointment
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The problem will be discussed in detail.
A family tree will be drawn
A medical examination may be carried out
The doctor or Genetic Counsellor will explain
their findings and discuss all the options.
The patient will be encouraged to ask questions
Blood tests may be offered.
A plan may be made for further information
gathering tests, or another appointment.
A letter is sent to the patient and GP
What does a genetics service offer?
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Genetic Testing
Diagnosis
Genetic counselling
Patient information
Speciality services and clinics
Education and training
Telephone advice
Should I Refer?
• Couple in late 20s - she has 1 child by
previous partner. No problems with
conceiving or miscarriages with first
partner
• Been together a few years and trying
for family - 5 miscarriages around 10-12
week time
• Two ectopic pregnancies and now has
no fallopian tubes
Options
• Draw family tree, include both partners
ask about
– Miscarriages in other family members
– Individuals with learning difficulties
Send bloods for Chromosomes
Refer for Genetic Counselling
What happened?
• Bloods for Chromosomes sent
• Female partner normal karyotype
• Male partner’s report states that the
quality of the sample was such that
they could not exclude any subtle
translocation
Reciprocal Translocation
7
7
7 10 10
Normal
7
10 10
7 10 der7 der10
Carrier
7 10 der7 der10
7 der7 10 10
Unbalanced
7 7 10 der10
Unbalanced
Genetic Testing
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Diagnostic
Carrier
Prenatal
Pre-implantation Genetic Diagnosis
Predictive
Diagnostic Genetic Tests
A diagnostic genetic test is performed to:• Confirm a clinical diagnosis
• IF a family history of cancer indicates a
genetic predisposition to develop cancer
Methods used
• Cytogenetic to look at chromosomes
• Molecular to look for gene alterations
Carrier Test
When there is a known genetic condition in the
family and other family members are at risk of
being a carrier.
Being a carrier does not have any implications
for their own health but may have implications
for future pregnancies.
Examples
– Cystic Fibrosis
– Chromosomal translocation
Prenatal Test
• Prenatal tests are available if:
– known familial genetic mutation
– known chromosomal abnormality
– high risk identified by a screening programme
• Prenatal tests are invasive
– Chorionic Villus sample performed from 11
weeks
– Amniocentesis performed from 15 weeks
Chorionic Villus Sample
Amniocentesis
Pre Implantation Genetic Diagnosis
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Available for limited number of conditions
Assisted conception
Analysis of a single cell from 8 cell embryo
Up to 2 unaffected embryos transferred
Approx 1 in 4 couples achieve a pregnancy
Predictive Test
In dominant genetic conditions, if the
individual inherits the gene alteration they
will:
– develop the condition at a later stage,
e.g. Huntington’s Disease
–be at increased risk of developing a
cancer in families with a family history
and a known gene alteration
Case study:
Is my baby at risk of
cystic fibrosis?
Jane Hobson is in the early stages of
pregnancy and is consulting you 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 screening programme.
Drawing a pedigree
Pedigree Symbols
Male
Female
Marriage / Partnership
(horizontal line)
/
Partnership that has
ended
Person whose sex is
unknown
P
Pregnancy
Offspring (vertical line)
Miscarriage
X weeks
Affected Male & Female
Carrier Male & Female
Parents and Siblings
Practicalities
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Start in the middle of the page
Use the standard symbols
Be systematic with questions
Try to find out about three generations
Ask sensitively about:
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Children from other relationships
Miscarriages and stillbirths
Disabilities and serious illnesses
Consanguinity
Causes of death, particularly premature
Family History
• Jane (28) is 6 weeks pregnant
• Jane’s husband is Christopher (29)
• This is their first baby
Christopher Hobson
29
Jane
28
P
6 weeks
Family History
• Christopher is an only child.
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• His father is William (60)
• His mother is Margaret (59)
• They are both alive and well
William Hobson
60
Margaret
59
Christopher Hobson
29
Jane
28
P
6 weeks
Family History
• Jane has one brother John (34)
• Jane and John’s father George Whitehead
died at the age of 66
• Jane and John’s mother Joan (64) is alive
and well
William Hobson
60
Margaret
59
Christopher Hobson
29
George Whitehead
Died age 66
Jane
28
P
6 weeks
Joan
64
John Whitehead
34
Family History
• Jane’s brother John has one son David (10)
to his first wife Alice (33).
• Their marriage ended in divorce
William Hobson
60
Margaret
59
Christopher Hobson
29
Joan
64
George Whitehead
Died age 66
Jane
28
Alice
33
John Whitehead
34
P
6 weeks
David
10
Family History
• John’s second wife is Christine (29)
• Christine had a miscarriage at 9 weeks
• They then had a son Richard (4) who has
Cystic Fibrosis
William Hobson
60
Margaret
59
Christopher Hobson
29
Joan
64
George Whitehead
Died age 66
Jane
28
Alice
33
John Whitehead
34
P
6 weeks
Christine
29
9 weeks
David
10
Richard
4
Cystic Fibrosis
William Hobson
60
Margaret
59
Christopher Hobson
29
George Whitehead
Died age 66
Jane
28
Joan
64
Alice
33
John Whitehead
34
P
6 weeks
Christine
29
9 weeks
David
10
Richard
4
Cystic fibrosis
From the family pattern, who must be carriers for
cystic fibrosis?
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
William Hobson
60
Margaret
59
Christopher Hobson
29
George Whitehead
Died age 66
Jane
28
Joan
64
Alice
33
John Whitehead
34
Christine
29
or
P
6 weeks
9 weeks
David
10
Richard
4
Cystic fibrosis
Is the probability of Jane Hobson being a carrier
for Cystic Fibrosis sufficiently high to offer testing?
Joan
William Hobson
60
Margaret George Whitehead
Died age 66
59
Christopher Hobson
29
Jane
28
Joan
64
Alice
33
John Whitehead
34
P
6 weeks
Christine
29
9 weeks
David
10
Assume Jane was tested and found to be a carrier.
Richard
4
Cystic fibrosis
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
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
ancestry = 1 in 25)
Jane’s risk
of being a
carrier
1
X
X
Christopher’s
risk of being
a carrier
1
25
X
X
Chance of
passing on two
copies of gene
alteration for CF
1
4
=
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Risk of baby
being affected
by CF
1
100
William Hobson
60
Margaret
59
Christopher Hobson
29
Joan
64
George Whitehead
Died age 66
Jane
28
Alice
33
John Whitehead
34
P
6 weeks
Christine
29
9 weeks
David
10
Richard
4
Cystic fibrosis
When should specialist genetic advice be sought?
William Hobson
60
Margaret
59
Christopher Hobson
29
Joan
64
George Whitehead
Died age 66
Jane
28
Alice
33
John Whitehead
34
P
6 weeks
Christine
29
9 weeks
David
10
Richard
4
Cystic fibrosis
Which other family members should be offered carrier status
testing?
Supporting Genetics Education for Health
www.geneticseducation.nhs.uk
Haemochromatosis
• AR, common mutations C282Y and H63D
• If C282Y/C282Y or C282Y/H63D 1-3 yearly
screening
– fasting transferrin saturation and serum
ferritin
• Refer if
– >50% transferrin saturation
– >300mcg/l ferritin in men and post menopausal
women
– >200 mcg/l in premenopausal women
Alpha1 Antitrypsin Deficiency
• MSZ Phenotype
• SZ and ZZ
– Advise re: smoking and alcohol
– Check baseline lung function