Genetics in general practice

Question 1

What are the key family history quesyions helpful in General Practice?

Answer 1

• Heart disease in close relatives before 60
• Type 2 DM in close relatives?
• Melanoma on close relatives?
• Bowel cancer in close relatives before 55?
• More than one relative on the same side has had bowel cancer at any age?
• Close male relatives with prosate cancer before 60?
• Close female relatives have had ovarian cancer ?
• Any close relatives have had breast cancer before 50?
• More than one relative on same side of family with breast cancer at any age?
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Question 2

What are the clinical and ethical considerations before offering patients a genetic test?

Answer 2

• Fully inform the purpose and family/personal implications of the test before obtaining consent
• Inform patients that they have a duty to inform life insurers of the test result when applying for a new policy or altering an existing policy
• Patient should be encouraged and supported to share the information with their relatives

Question 3

What genetic tests are available on MBS for specific indications?

Answer 3

• Haemochromatosis
• Fragile X Syndrome
• Facotr 5 leiden
• Inherited thrombophilias
• Karyotyping and chromosomal microarrays for Ix of developmental delays

Question 4

What are the key aspects in Haemochromatosis testing and diagnosis?

Answer 4

1)Test the following patients for fasting transferrin saturation and serum ferritin concentration

• Liver disease of unknown cause
• All first degree relatives with haemochromatosis or known mutation in the HFE gene
• Patients with conditions that could be a complication of HFE (diabetes, atypical arthritis, cardiomyopathy, erectile dysfunction or chronic fatigue)

2) If fasting transferrin >45% or serum ferritin >250 on more than one occasion, test for HFE mutations

• If HFE mutation is identified, discuss options of further testing/counselling
• Children of C282Y heterozygotes should only be tested if the othe rparents also has C282Y mutation
• Children not testes until 18 if asymptomatic
• Other first degree relatives of C282Y heterozygotes should be testes with iron studies; if positive for genetic testing

3) MBS covers HFE gene testing for patients with

• Raised ferritin or transferrin saturation levels on more than 1 occasion or
• First degree relatives diagnosed with HH or with two HFE mutations

Question 5

What are the key aspects in screening for Neurofibromatosis?

Answer 5

1) NF 1 (Autosomal dominant) is characterised by multiple cafe au lait spots, inguinal, axillary frckling and multiple neurofibroams

• Genetic testing not necessary for diagnosis after birth in children born to parent with NF 1
• Prenatal genetic testing possible when family specific gene is knwon

2) NF 2 (AD) is characterised by bilateral vestibular schwannomas, gradual hearing loss, balance problems and tinnitus

• Pre-symptomatic genetic testing is available to blood relatives of individuals in whom a mutation has been identified
• Autosomal dominant pattern of inheritance in both; 50% of cases due to sporadic mutation

Question 6

What are the key aspects of genetic testing in patients with skin cancer?

Answer 6

1) High risk of skin cancer is noted in

• Patients with multiple dysplastic naevi and with a family history of melanoma in themselves or in a first degree relative
• Prevention advise
• Examination of skin and advise on self examination preferably with photographs
• Review 3-12 months

2) Increased risk of skin cancer is noted in

• Family history of melanoma in first degree relatives
• Fair complexion
• A tendency to burn rather than tan
• Presnec of freckles, light eye colour, light or red hair colour
• Age >30 year (>50 most at risk)
• Presence of solar lentigines
• Past history of non melanoma skin cancer (age <40 higher risk)
• People with childhood high levels of UV exposure
• Episodes of sunburn in childhood
• Annual skin examiation and self examiantion advise

Question 7

What are the key aspects of prostate cancer testing?

Answer 7

1) High risk for prostate cancer is seen in

• Men with one or more relatives diagnosed under 65 years
• Men with a first degree relative with familial breast cancer (BRCA1 or 2)
• Routine screening is not recommended
• Screen when the man specifically asks for it and he is fully counselled on the rpos and cons

Question 8

What are the key aspects of breast cancer testing?

Answer 8

1) Potentially high risk is noted in
a) Women who are at potentially high risk of ovarian cancer
b) Two first or second degree relatives on one side of the family diagnosed with breast or ovarian cancer plus one or more of the following

• Additional relatives with breast or ovarian cancer
• Breast cancer diagnosed before 40
• B/l breast cancer
• Breast and ovarian cancer in the same woman
• Ashkenazi Jewish ancestry
• Breast cancer in a male relative
• One first or second degree relative diagnosed with breast cancer <45 plus another first or second degree relative on the same side diagnosed with sarcoma <45
• Members of the family in which the presence of a high risk breast cancer gene mutation has been established

c) Clarify risk at nbocc.org.au and advise referral to a cancer specialist or family cancer clinic
d) Ongoing surveillance strategies include regualr clinical breast examination, mammography, MRI or US and consideration of ovarian cancer risk. The relative risk in this group is 1:4 to 1:8
2) Moderately increased risk includes

• One first degree relative <50 or two first degree relatives on the same side with breast cancer or two second degree relatives on the same side of family with atleast one before 50 years
• Clarify risk at canceraustralia.gov.au; breast awareness and consider referral to a family cancer clinic
• Mammogram every 2 years from age 50 or from 40 if a first defree relative had cancer <50

Question 9

What are the key aspects of ovarian cancer testing?

Answer 9

Higher risk is noted in

• Family history of ovarian cancer especially first degree relatives and more than one relative
• Presence of BRCA 1 or BRCA2
• Consider increased frequency fo screening for breast and colorectal cancer in high risk groups
• Routine screening for ovarian cancer not recommended
• women on OCP or carried a pregnancy to term have a lowe risk of the population average

Question 10

What are the key aspects of colorectal cancer testing?

Answer 10

1) High risk is noted in the following

• 3 or more first degree relatives on the same side of family with colorectal cancer(suspecyed lynch syndrome (HNPCC) or
• Two or more first or second degree on the same side with CRC with either multiple CRC in the one person or CRC <50 or a family member who has or had Lynch related cancer or
• One first or second degree relative with CRC with a large number of adenomas or
• Someone in the family in whom the presence of a higher risk mutation int eh APC or one of the mismatch repair genes
• Refer to bowel cancer specialists to plan appropriate surveillance and genetic screening of affected relatives
• Colonoscopy in FAP every 12 months from age 12-15 years to age 30-35 years and then every 3 years after 35
• 1-2 yearly colonoscopy from age 25 years or 5 years earlier than youngest affected member of the family(whichever is earliest and aspirin 100mg daily for Lynch Syndrome

2) Moderate risk

• Asymptomatic people with one first degree relative with CRC before 55 or
• Two first defree or one first and one second degree relative on the same side of the family with CRC at any age
• Colonoscopy every 5 years from 50 years or 10 years younger than the age of first diagnosis of CRC. CT colonography acceptable if colonoscopy contraindicated

3) Average or slightly increased risk

• No personal history of bowel cancer, UC and no family history of CRC or
• One first or second degree relative with CRC diagnosed at 55 or older
• FOBT every 2 years from age 50

Question 11

What are the key aspects of screening for Type 2 DM?

Answer 11

1) High risk

• AUSDRISK 12 or more
• All people with a previous cardiovascular event
• Women with a history of GDM
• Women with PCOS
• Patients on antipsychotic drugs
• Fasting BSL every 3 years

2) Increased risk

• Age >40
• Aboriginal and Torres Strait Islanders
• AUSDRISK every 3 years

Question 12

What are the key aspects for screening for familial hypercholesterolaemia?

Answer 12

1) Following features may be indicative.

• Premature IHD (men aged <55y, women <60years)
• First degree relative with premature IHD(men aged <55 and women <60years)
• Total cholesterol >7.5 or LDL >4.9)
• First degree relative with total cholesterol >7.5 or LDL-C >4.9
• Tendon xanthomatas or arcus senilis <45 years

2) Assess probability of having family history with either Dutch Lipid Clinic Network Criteria(DLCN) or Modified UK Simon Broome Criteria (MUKSB). Score >3 suggests possible family history
3) Genetic testing is available through cardiac specialists or genetics services

Question 13

What are the key aspects for screening for screening for Fragile X and other causes of developmental delay?

Answer 13

1) Children or adults of either sex with one or more of

• Developmental delay including intellectual delay of unknwon cause
• Autistic features
• ADHD
• Speech and language problems
• Social and emotional problems
• A female with a history of primary ovarian insufficiency or premature menopause (<40years)
• Adults with ataxia, balance problesm and Parkinsonism
• A relative with a fragile X mutation

2) Chromosome analysis and DNA test available on MBS. Refer to genetics services
3) Diagnosis can be made at any age and GPS need to be aware of the features

Question 14

What are the key aspects for screening for hereditary thrombophilias?

Answer 14

1) Criteria for screening include

• DVT <50 years
• Spontaneous thrombosis in absence of recognised risk factors
• Recurrent thrombosis
• Family history of thrombosis
• Thrombosis in unusual sites(CNS, up[per limb, abdominal veins)
• Still birth or foetal death in utero

2) A thrombophilia screen includes factor 5 Leiden, prothrombin variants, antithrombin 3 deficiency, protein C and protein S for deficiencies, activated protein C resistance
3) These tests are available on MBS only when a personal history of proven VTE or PE or a first degree relative has a proven defect on testing

Question 15

What are the key aspects for carrier screening for haemoglobinopathies?

Answer 15

1) People have increased risk if from following ancestries

• Southern Europe
• African and American Carribean
• Middle eastern
• Chinese
• South east Asia and Indian subcontinent
• Central Asia
• New Zealand Maori
• Pacific Islander
• Northern territory and Northern Western Australian communities
• South American

2) MCV, MCH, ferritin, iron levels and haemoglobin electrophoresis
3) Test couple before pregnancy or in first trimester
4) Seek advise from genetic services about DNA testing especially for alpha thalassaemia carriers

Question 16

What are the genetic services available in Australia?

Answer 16

• Genetic services run by state health andf outreach clinics
• **Direct to consumer genetic testing **has not been verified by NHMRC and has warned consumers to carefully consider unintended consequences for insurance, privacy and emotional health