Preventive activities in general practice 7th edition

Introduction and user guide

Preventive activities before pregnancy

Genetic counselling and testing

Preventive activities in children and young people

Preventive activities in middle age

Preventive activities in older age

Communicable diseases

Prevention of chronic disease

Prevention of vascular and metabolic disease

Early detection of cancers

Psychosocial

Screening tests of unproven benefit

Appendices

Disclaimer

Genetic counselling and testing

Genetic counselling and testing Age range table
Age	0 - 9	10 - 14	15 - 19	20 - 24	25 - 29	30 - 34	35 - 39	40 - 44	45 - 49	50 - 54	55 - 59	60 - 64	65 - 69	70 - 79	>80
			17	X	X	X	X	X	X	X	X	X	X

Genetic counselling and testing Age range table

Age

0 - 9

10 - 14

15 - 19

20 - 24

25 - 29

30 - 34

35 - 39

40 - 44

45 - 49

50 - 54

55 - 59

60 - 64

65 - 69

70 - 79

>80

There is insufficient evidence to recommend screening the population utilising genetic testing, except for pregnant women and neonates (C). Genetic tests are appropriate for certain conditions where the individual is considered to be at high risk (A).

In order to identify patients who may potentially benefit from genetic testing, the GP must ensure that a comprehensive family history is taken from all patients (including first degree or second degree relatives) (A) and regularly updated.

The presence of genetically determined disease may be suggested by the following:

increased frequency and early onset of cancers in families

unexplained intellectual disability

birth defects

multiple pregnancy losses or stillbirth or early death, or

children with multiple congenital abnormalities.

Also, patients of particular ethnic backgrounds may be at higher risk and may benefit from genetic testing. General practitioners should consider referral to, or consultation with, a genetic service (general or cancer genetics) for testing, as test results are not straightforward. Testing often involves complex, ethical, social and legal issues.

Genetic counselling and testing: Risk
Who is at higher risk?	What should be done?	How often?	Level of evidence and references
Breast and ovarian cancers
See Chapter 9.3 Breast cancer
Colon cancer
See Chapter 9.5 Colorectal (bowel cancer)
Cystic fibrosis
High risk Those with a family history of cystic fibrosis (CF), or whose relative carries a known CF mutation Those whose partner is affected or is a known carrier of CF Those whose partner is from northern European, Ashkenazi Jewish background who are consanguineous (ie. cousins married to each other) Men with infertility suspected or due to congenital absence of the vas deferens	Refer for testing, and as required for genetic counselling	Before pregnancy or in first trimester or preimplantation genetic diagnosis (PGD)	III B 60,62
Down syndrome
High risk Women of advanced maternal age (≥35 years of age) Parent with a chromosomal rearrangement (eg. translocation of chromosome 21)	Maternal serum/ultrasound screening	In first or second trimester	V C 62-64
Very high risk Women who have had a previous Down syndrome pregnancy Women with positive maternal serum screening/nuchal translucency ultrasound in first trimester or maternal serum screening in second trimester	Fetal diagnostic genetic testing	In first or second trimester	V C 63
Hereditary haemochromatosis
High risk Patients with liver disease of unknown cause, including patients with suspected alcoholic liver disease All first or second degree relatives of patients with haemochromatosis, or an altered HFE gene Patients with conditions that could be a complication of haemochromatosis, ie. diabetes mellitus, atypical arthritis, cardiomyopathy, erectile dysfunction or chronic fatigue	Test for transferrin saturation and serum ferritin concentration. If fasting transferrin saturation >45% or ferritin is raised on more than one occasion, test by DNA typing Test all first degree relatives of carriers (homozygous for C282Y gene or compound heterozygotes) with DNA typing and iron studies Children of C282Y heterozygotes should only be tested if the other parent is also heterozygous for the C282Y mutation. Children in affected families should not be tested until 18 years of age Other first degree relatives of C282Y heterozygotes should be tested with DNA typing and iron studies	Repeat every 2-5 years	II A 62,65-67
Haemoglobinopathies and thalassaemias
Higher risk Patients of southern Mediterranean, African, Middle East, transcaucasus, central Asia, Indian subcontinent and southeast Asian background who are contemplating pregnancy, particularly where there is a family history of haemoglobinopathy (In some states with higher prevalence of at risk ethnic groups all pregnant women are screened by mean corpuscular volume [MCV])	MCV Haemoglobin electrophoresis	Before pregnancy	III B 68,69
Fragile X syndrome
Higher risk Women with a personal or family history of: a male or female with intellectual disability, developmental delay or learning disability of unknown cause a male with autism-like characteristics undiagnosed intellectual disability or fragile X syndrome individuals with a previous fragile X cytogenetic test that was negative or inconclusive a female with a history of premature menopause (<40 years of age)⁷⁰ a male with ataxia and parkinsonism	Karyotyping (cytogenetic studies) and DNA studies of affected boy, followed by testing mother or affected son or daughter Diagnostic test for males with ataxia, tremor or dementia who have a family history of fragile X syndrome	Before pregnancy	I A 71 IV B 72 IV A 73

Genetic counselling and testing: Risk

Who is at higher risk?

What should be done?

How often?

Level of evidence and references

Breast and ovarian cancers

See Chapter 9.3 Breast cancer

Colon cancer

See Chapter 9.5 Colorectal (bowel cancer)

Cystic fibrosis

High risk

Those with a family history of cystic fibrosis (CF), or whose relative carries a known CF mutation
Those whose partner is affected or is a known carrier of CF
Those whose partner is from northern European, Ashkenazi Jewish background who are consanguineous (ie. cousins married to each other)
Men with infertility suspected or due to congenital absence of the vas deferens

Refer for testing, and as required for genetic counselling

Before pregnancy or in first trimester or preimplantation genetic diagnosis (PGD)

III B 60,62

Down syndrome

High risk

Women of advanced maternal age (≥35 years of age)
Parent with a chromosomal rearrangement (eg. translocation of chromosome 21)

Maternal serum/ultrasound screening

In first or second trimester

V C 62-64

Very high risk

Women who have had a previous Down syndrome pregnancy
Women with positive maternal serum screening/nuchal translucency ultrasound in first trimester or maternal serum screening in second trimester

Fetal diagnostic genetic testing

In first or second trimester

V C 63

Hereditary haemochromatosis

High risk

Patients with liver disease of unknown cause, including patients
All first or second degree relatives of patients with haemochromatosis, or an altered HFE gene
Patients with conditions that could be a complication of haemochromatosis, ie. diabetes mellitus, atypical arthritis, cardiomyopathy, erectile dysfunction or chronic fatigue

Test for transferrin saturation and serum ferritin concentration. If fasting transferrin saturation >45% or ferritin is raised on more than one occasion, test by DNA typing

Test all first degree relatives of carriers (homozygous for C282Y gene or compound heterozygotes) with DNA typing and iron studies

Children of C282Y heterozygotes should only be tested if the other parent is also heterozygous for the C282Y mutation.

Children in affected families should not be tested until 18 years of age

Other first degree relatives of C282Y heterozygotes should be tested with DNA typing and iron studies

Repeat every 2-5 years

II A 62,65-67

Haemoglobinopathies and thalassaemias

Higher risk

Patients of southern Mediterranean, African, Middle East, transcaucasus, central Asia, Indian subcontinent and southeast Asian background who are contemplating pregnancy, particularly where there is a family history of haemoglobinopathy

(In some states with higher prevalence of at risk ethnic groups all pregnant women are screened by mean corpuscular volume [MCV])

MCV

Haemoglobin electrophoresis

Before pregnancy

III B 68,69

Fragile X syndrome

Higher risk
Women with a personal or family history of:

a male or female with intellectual disability, developmental delay or learning disability of unknown cause
a male with autism-like characteristics
undiagnosed intellectual disability or fragile X syndrome
individuals with a previous fragile X cytogenetic test that was negative or inconclusive
a female with a history of premature menopause (<40 years of age)⁷⁰
a male with ataxia and parkinsonism

Karyotyping (cytogenetic studies) and DNA studies of affected boy, followed by testing mother or affected son or daughter

Diagnostic test for males with ataxia, tremor or dementia who have a family history of fragile X syndrome

Before pregnancy

I A 71
IV B 72
IV A 73

Genetic counselling and testing: Test
Test	Technique	References
Family history	Ideally the following information will be collected for a full genetic assessment: information from three generations of both maternal and paternal family line record if alive or dead record age of onset of disease Identify affected first or second degree male or female relatives on either side of the family	63,74
Genetic testing	Genetic screening should be undertaken after the family history has been established in detail. Genetic testing should be conducted under the supervision of a clinical geneticist, an appropriate specialist or ethically approved clinical research group, and should be supported by appropriate counselling. Fragile X syndrome and haemachromatosis may be exceptions to this	62
Breast cancer	If a woman wishes to clarify her genetic risk or that of her family, or wishes to consider risk reducing surgery, discuss referral to a specialist family cancer clinic for advice, appropriate counselling and management. Genetic testing may be appropriate No reduction in mortality from prophylactic mastectomy has been shown Oral contraceptive medication reduces risk of ovarian cancer for women with BRCA1 or BRCA2 mutations but has no effect on risk of breast cancer	75 76-81
Maternal Down syndrome screening	First trimester: free beta human chorionic gonadotrophin (HCG), pregnancy associated plasma protein and fetal ultrasound nuchal translucency screen at 12 weeks Second trimester: serum screening – beta HCG, unconjugated oestriol, alpha-fetoprotein	63, 64
Fetal diagnostic genetic testing for Down syndrome	First trimester: chorionic villus sampling Second trimester: amniocentesis	63

Genetic counselling and testing: Test

Test

Technique

References

Family history

Ideally the following information will be collected for a full genetic assessment:

information from three generations of both maternal and paternal family line
record if alive or dead
record age of onset of disease

Identify affected first or second degree male or female relatives on either side of the family

63,74

Genetic testing

Genetic screening should be undertaken after the family history has been established in detail. Genetic testing should be conducted under the supervision of a clinical geneticist, an appropriate specialist or ethically approved clinical research group, and should be supported by appropriate counselling. Fragile X syndrome and haemachromatosis may be exceptions to this

Breast cancer

If a woman wishes to clarify her genetic risk or that of her family, or wishes to consider risk reducing surgery, discuss referral to a specialist family cancer clinic for advice, appropriate counselling and management. Genetic testing may be appropriate

No reduction in mortality from prophylactic mastectomy has been shown

Oral contraceptive medication reduces risk of ovarian cancer for women with BRCA1 or BRCA2 mutations but has no effect on risk of breast cancer

76-81

Maternal Down syndrome screening

First trimester:
- free beta human chorionic gonadotrophin (HCG), pregnancy associated plasma protein and fetal ultrasound
- nuchal translucency screen at 12 weeks
Second trimester:
- serum screening – beta HCG, unconjugated oestriol, alpha-fetoprotein

63, 64

Fetal diagnostic genetic testing for Down syndrome

First trimester:
- chorionic villus sampling
Second trimester:
- amniocentesis

Genetic counselling and testing: Terminology
Terminology	Purpose
Diagnostic testing	To make or confirm a diagnosis of a specific disorder in a person who generally already has signs or symptoms of that disorder
Genetic carrier testing	To determine whether or not the person has a genetic or chromosomal abnormality that does not generally affect that person’s health but increases his/her chance of having children with the disorder in question
Prenatal testing	Performed on a fetus in utero where there are ‘at risk’ parents, in order to inform decisions about termination of pregnancy or for therapeutic or surgical interventions

Genetic counselling and testing: Terminology

Terminology

Purpose

Diagnostic testing

To make or confirm a diagnosis of a specific disorder in a person who generally already has signs or symptoms of that disorder

Genetic carrier testing

To determine whether or not the person has a genetic or chromosomal abnormality that does not generally affect that person’s health but increases his/her chance of having children with the disorder in question

Prenatal testing

Performed on a fetus in utero where there are ‘at risk’ parents, in order to inform decisions about termination of pregnancy or for therapeutic or surgical interventions

Guidelines for preventive activities in general practice 7th edition

Full index

Introduction and user guide

Preventive activities before pregnancy

Genetic counselling and testing

Preventive activities in children and young people

Preventive activities in middle age

Preventive activities in older age

Communicable diseases

Prevention of chronic disease

Prevention of vascular and metabolic disease

Early detection of cancers

Psychosocial

Oral hygiene

Glaucoma

Urinary incontinence

Osteoporosis

Screening tests of unproven benefit

References

Appendices

Glossary

Acronyms

Acknowledgements

Disclaimer

Genetic counselling and testing