Daughter Daughter Son Son

Parents

Gametes

At conception

X-LINKED INHERITANCE WHERE THE MOTHER IS A CARRIERFather Mother

X Y XX

(Carrier) (Affected)

(Carrier)(Unaffected)

Fragile X Syndrome

Supporting Genetics Education for Health

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Fragile X Syndrome is the most common identifiable cause of inherited intellectualdisability (mental handicap). It can cause a wide range of difficulties with learning,as well as social, language, attentional, emotional and behavioural problems.

Duchenne Muscular Dystrophy

Fig. 1.4 ©Scion Publishing Ltd

Histology photos courtesy of Dr Richard Charlton.

(a) Affected boys stand up by bracing their arms against their legs (Gower’s manoeuvre) because their proximal (eg muscles are weak. (b) and (c) Muscle histology (Gomori trichrome stain). Normal muscle (b) shows a regular architecture of cells with dystrophin (brown stain) on all the outer membranes. (c) Shows muscle from a 10-year-old affected boy. Note the disorganisation, invasion by fibrous tissue and complete absence of dystrophin. Histology photos courtesy of Dr Richard Charlton, Newcastle upon Tyne.

Ethical Issues 1

Mr P was recently diagnosed with ADPKD. Having realised each of his children has a 50% chance of having inherited the condition from him, Mr P asks the 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.

Consider the statement above to what extent do you agree or disagree with it?

Ethical Issues 2• Duchenne Muscular Dystrophy (DMD) is a progressive

neuromuscular disorder affecting ~ 1 in 3000 male births.• Boys with DMD are diagnosed between 4-5 years In

about 2/3 cases, the mother is a carrier. • No treatment

Neonatal screening of all male births should be performed to identify affected boys so their mothers can be tested to see if they are carriers and so at risk of having further affected pregnancies

Making a referral

• Draw a family pedigree• Patient’s date of birth, address, telephone

number, GP, NHS Number• Affected / carrier person’s name, Date of Birth,

genetic condition, relationship to patient• Details of anyone already known to genetics

Taking a sample

• Ensure the patient is aware of the possible implications of the result for themselves and other family members before the blood sample is taken.

• Obtain consent for the procedure, document whether

the patient is happy for results to be shared with other relevant health professionals and family members.

• Arrange how, when and from whom the patient will

receive the results.

Sending a blood sample to Genetics 1Single gene disorder• 5ml venous blood sample in an EDTA tube • Clearly label blood tubes with 3 reference points,

name, date of birth and NHS number

• On a form need the same details +– details of the test required– details of affected/carrier family members– Clearly mark as Urgent with weeks gestation– Telephone contact of person giving result

Sending a blood sample to Genetics 2

• For Autosomal Recessive conditions such as Cystic Fibrosis, Tay Sachs, send a sample from both partners

• Send each partner on a separate form with linking identifiers

Sending a blood sample to Genetics 3

Chromosome Disorders: • 5ml venous blood sample in a Lithium

Heparin tube • Details as before

Genetics in Primary Care Module

GPS_06_001 Why does genetics matter in primary care practice?

GPS_06_003 Interpreting family histories: Autosomal conditions

GPS_06_004 Interpreting Family Histories and Identifying Patients Part 2: Sexlinked Conditions and Conditions with Variable Patterns of Inheritance

GPS_06_006 Talking genetics: Communicating genetic information

Supporting Genetics Education for Health

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Resources• Familial Hypercholesterolaemia scenarios • Collecting, Recording and Interpreting Family

History Information • 'Taking a Family History' Videos • PowerPoint files of clinical photographs • PowerPoint files on specific genetic conditions • PowerPoint files explaining core genetic

concepts • The Genomic Basis of Therapeutics series • Dietetics "Genetics and Obesity"

Supporting Genetics Education for Health

www.geneticseducation.nhs.uk

Supporting Genetics Education for Healthwww.geneticseducation.nhs.uk

What Impact is Genetics likely to make on the NHS in

the future?

Supporting Genetics Education for Health

www.geneticseducation.nhs.uk

ALL (acute lymphoblastoidleukemia) and AML (acute myeloid leukemia) cells look alike, but microarrays distinguish them

Oncology

RED = over-expression of genes

Especially using genetic data to sub-type tumours – informing treatment and management

Congenital hypothyroidism

PKU

Newborn BloodspotCards

Congenital hypothyroidism

PKU

MCADD

Cystic Fibrosis

Sickle Cell Disease & Beta thalassaemia major

Newborn Screening

Down’s Syndrome Screening

Combined Test 11 – 14+2 weeks:- Nuchal Translucency - Serum PAPPA and Free βhCG

Serum Screening 15 – 20 weeks: - AFP, βhCG, Oestriol, Inhibin A

The future – Free cell fetal DNA

Down’s Syndrome

• 95% Regular Trisomy• 4% Translocation • 1% Mosaic

1414 21 21

1414 21 21 14 2114

21

1414 2114

21

2114

21

14 21

211414

21

14

Normal Carrier Trisomy 14 Trisomy 21

Robertsonian Translocation

CardiologyPeople with inherited risk of cardiac problemsincreasingly identified

Screening & treatment Available - saving lives

Pharmacogenomics Genetic information can identify the right treatment for

a patient

e.g. Abacavir (used to treat HIV & AIDS)• Gene test now used routinely

in UK to identify people who might be hypersensitive

• IMPACT – many thousands of adverse drug reactions avoided (5-10% had adverse reaction in the past & response could be fatal)

Abacavir

Please get in touch if you want further information/support:

Susan.fairgrieve@nuth.nhs.uk0191 241 8742

Institute of Genetic MedicineCentral Parkway

Newcastle Upon TyneNE1 3BZ

NGEDC website:www.geneticseducation.nhs.uk

Thank you

Any Questions?