Supporting Genetics Education for Health Practical Genetics for Primary Care Kate May Genetic...

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Practical Genetics for Primary Care

Kate May

Genetic Counsellor

Nottingham Clinical Genetics Service,

Nottingham City Hospital

Telephone: 0115 9627728

Email: [email protected]


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


Cumulative pace of gene discovery 1981-2003


Genes and ill-health: for specialists only?

Source: NHGRI 2006


When might a GP see genetics in

practice?

Clinical management

Communicating genetic information

Identifying patients


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


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?


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?


Is my baby at risk of cystic fibrosis?


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.


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


CF video family history clip


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


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


William60

Joan

63

P6 weeks

Julie27

David10


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


William60

Joan63

P

6 weeks

Julie27

David10


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


William 60

Joan63

P

6 weeks

Julie27

David10


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


William 60

Joan63

P

6 weeks

Julie27

David10


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’


Familial Cancer Genetics

• When to make a referral

• Who to refer to

• Sources of information and advice


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


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.


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) - 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

784842George

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.


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


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


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


Sources of information

• Local or national guidelines e.g NICE

• Discussing with a colleague

• Contact the local CGS

• Internet

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

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 ,


National Genetics Education and Development Centre

http://www.geneticseducation.nhs.uk/


To refer or not refer?

• Please call Nottingham Regional Clinical

Genetics Service for advice and information

• Tel: (0115) 9627728


Referral Address

Nottingham Clinical Genetics Service, City Hospital Campus,The Gables, Gate 3, Hucknall RoadNottinghamNG5 1PB

Tel 0115 9627728


Ethical Issues in Primary Care Genetics


Mr P was recently diagnosed with autosomal dominant polycystic kidney disease (ADPKD). Having realised that each of his children has a 50% chance of having inherited the condition from him, Mr P asks his GP to organise a kidney ultrasound for his two children aged 10 and 7, to see if they have inherited the condition. The GP should do so.

Strongly agree

Agree Neutral Disagree Strongly disagree

Consider the statement above and indicate the extent to which you agree or disagree with it.


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.


Strongly agree



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




John and Susan come in to your surgery. You have seen quite a lot of them over the past two years, as their second child Michael was born with Sickle Cell Anaemia. They have recently had another child, Rebecca. Newborn screening showed that Rebecca is a carrier of sickle cell anaemia, and this information was routinely reported to parents.

John and Susan also have a healthy older daughter, Mary, 8yrs. Her carrier status is unknown, as screening of newborns was not yet done routinely when she was born. As they already have one ill child and one carrier child, John and Susan are also quite anxious about Mary's carrier status for this condition. They request that you organise a referral for carrier testing.

What should you do?

Test Uncertain 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



Thanks so much for your time!

Kate May

Genetic Counsellor

Nottingham Regional Clinical Genetics Service, Nottingham City Hospital

Telephone: 0115 9627728

Email: [email protected]


Current and future developments

• Screening technology e.g. non invasive techniques

• Genetic profiling – genomic medicine• New technology in assisted reproduction• Treatments for genetic and non-genetic disorders

- Stem cells- Gene therapy

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