X-LINKED INHERITANCE WHERE THE MOTHER IS A CARRIER Parents Father Mother (Unaffected) (Carrier) Gametes X Y X X At conception Daughter Daughter Son Son (Carrier) (Affected)

Fragile X Syndrome Fragile X Syndrome is the most common identifiable cause of inherited intellectual disability (mental handicap). It can cause a wide range of difficulties with learning, as well as social, language, attentional, emotional and behavioural problems. Fragile X Syndrome is the most common known cause of inherited learning disabilities. It can cause a wide range of difficulties with learning, as well as social, language, attentional, emotional, and behavioural problems. The Fragile X chromosome, in the centre of the picture, shows the fragile site at the lower tip in contrast to the other normal chromosomes. The Fragile X gene has a number of repeats, which when there are greater than 200 repeats in a male will cause Fragile X syndrome Supporting Genetics Education for Health www.geneticseducation.nhs.uk

Duchenne Muscular Dystrophy (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. Most affected boys develop the first signs of difficulty in walking at the age of 1 to 3 years and are usually unable to run or jump like their peers, they often struggle to climb stairs and need to use a banister for support. Rising from the floor can also prove difficult. As the condition progresses boys with DMD are unable to walk as far or as fast as other children and may occasionally fall down. Some boys also have learning and or behavioural difficulties, which may begin to manifest at this stage. By about 8 to 11 years (rarely earlier or a little later) boys become unable to walk and by their late teens or twenties the condition is severe enough to shorten life expectancy. Information from Muscular Dystrophy Campaign website - http://www.muscular-dystrophy.org/assets/0000/7782/Duchenne_MD.pdf Fig. 1.4 ©Scion Publishing Ltd Histology photos courtesy of Dr Richard Charlton.

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 1 Single 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

Our new look home webpage

Follow the front page link to the e-learning section BMJ Learning The Centre has developed a two-module course for BMJ Learning entitled 'Genomics - an introduction for clinicians'. After completing this course, you should understand how genomics can be used to: Make a more accurate or specific diagnosis of disease Individualise treatment Predict the effects of drugs Develop new treatments Help in the management of cancer and infectious diseases. You should also feel more confident about explaining genomic principles to patients and start to consider where you might incorporate genomic tests into everyday clinical management. How to access the modules To access the modules you must set up an account at the BMJ Learning website, which is free to do. Completion of the modules will provide you with BMJ Learning certificates which can then be placed in your CPD portfolio. The following links go direct to the individual modules. - An introduction to genomics - Genomic medicine in the management of cancer and infectious diseases

Advise on the genetic tests available

Lots of new resources available including around genomic healthcare

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 The eGP project is a joint project of the RCGP and e-learning for healthcare and is funded by the Department of Health. It aims to produce electronic modules, each containing approximately 10 20 minute electronic sessions, covering the whole curriculum. These are the modules currently available. If GP trainees access e-learning, answer the questions and write some thoughts in the reflective practice box the system will automatically update their profile to say they have completed a genetics module.

Supporting Genetics Education for Health www.geneticseducation.nhs.uk

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 Health There is now an icon with an owl which denotes an expert’s comments Supporting Genetics Education for Health www.geneticseducation.nhs.uk

What Impact is Genetics likely to make on the NHS in the future?

Oncology Especially using genetic data to sub-type tumours – informing treatment and management RED = over-expression of genes ALL (acute lymphoblastoid leukemia) and AML (acute myeloid leukemia) cells look alike, but microarrays distinguish them Supporting Genetics Education for Health www.geneticseducation.nhs.uk 23

Newborn Screening Newborn Bloodspot Cards Congenital hypothyroidism MCADD - Medium chain Acyl Co-A Dehydrogenase Deficiency Congenital hypothyroidism PKU MCADD Cystic Fibrosis Sickle Cell Disease & Beta thalassaemia major Congenital hypothyroidism PKU

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

Robertsonian Translocation Normal Carrier Trisomy 14 Trisomy 21

Cardiology People with inherited risk of cardiac problems increasingly identified Screening & treatment Available - saving lives Eg. Long QT and hypertrophic cardiomyopathy Across UK – Cardiac Liaison nurses and Genetic Arrhythmia Clinics 28

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

Institute of Genetic Medicine Central Parkway Newcastle Upon Tyne Please get in touch if you want further information/support: Susan.fairgrieve@nuth.nhs.uk 0191 241 8742 Institute of Genetic Medicine Central Parkway Newcastle Upon Tyne NE1 3BZ NGEDC website: www.geneticseducation.nhs.uk

Thank you Any Questions?