Guidelines for preventive activities in general practice

The Red Book
Chapter 2. Genetic counselling and testing
☰ Table of contents

Age range chart

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

Genetic testing can be used for various purposes, from preconception planning (refer to Chapter 1. Preventive activities prior to pregnancy), during pregnancy, for neonates (newborn screening), during childhood and right through to adult-onset familial diseases (eg cancer, cardiac and neurodegenerative diseases).

In order to identify patients who may be at risk of a genetic disorder, a comprehensive family history must be taken from all patients, and this should be regularly updated. A family history should include first-degree and second-degree relatives on both sides of the family and ethnic background. Age of onset of disease and age of death should be recorded where available.

Increased frequency and early onset of cancers in families, premature ischaemic heart disease or sudden cardiac death, intellectual disability, multiple pregnancy losses, stillbirth or early death, and children with congenital abnormalities may suggest the presence of genetically determined disease. Patients of particular ethnic backgrounds may be at increased risk and may benefit from genetic testing for specific conditions. Possible consanguinity (eg cousins married to each other) should be explored, for example, by asking, ‘Is there any chance that a relative of yours might be related to someone in your partner’s family?’ General Practitioners (GPs) should consider referral to, or consultation with, a genetic service (general or cancer genetics) for testing because test results, which rely on sensitivity, specificity and positive predictive value, are not straightforward. Testing often involves complex ethical, social and legal issues. The time on waiting lists for genetic services is usually longer than one month, so direct consultation and liaison by telephone are necessary when the genetic advice could affect a current pregnancy. On the basis of current evidence, whole genome sequencing is not recommended in low-risk general practice populations (refer to Chapter 15. Screening tests of unproven benefit).

Clinical genetic services provide testing, diagnosis, management and counselling for a wide range of genetic conditions. Reasons for referral include:

  • diagnosis of a genetic condition
  • family history of a genetic condition
  • recurrence risk counselling (eg risk of recurrence in a future pregnancy)
  • pregnancy counselling (eg preconception, consanguinity)
  • prenatal screening and testing
  • presymptomatic and predictive testing for adult-onset disorders (eg cancer)
  • discussions surrounding genetic testing
  • arranging of genetic testing.

Services such as paternity testing or genetic testing/management of very common genetic conditions (eg haemochromatosis) are not provided by clinical genetic services.

Use of a simple family history screening questionnaire (FHSQ) can help identify individuals who may require a more detailed assessment of their family history of cancer, heart disease or diabetes (refer to Appendix 2A. Family history screening questionnaire for a published and validated FHSQ).1 This tool can be used as part of the patient assessment at their first visit to a practice. If a patient is uncertain about their family history, they can be asked to discuss the FHSQ with their relatives prior to completing the questionnaire. For patients with low literacy, the FHSQ may need to be completed with the support of a healthcare professional. A positive response to any question requires follow-up with a more detailed assessment of the family history. As family history can change, it is recommended that the FHSQ be repeated at least every years.

Table 2.1. Genetic testing: Identifying risks

Who is at risk?

What should be done?

How often?

Cystic fibrosis (CF)

Increased probability:
Northern European or Ashkenazi Jewish ancestry
Family history of CF or a relative with a known CF mutation
Where partner is affected or a known carrier of CF
Partners from Northern European or Ashkenazi Jewish backgrounds who are consanguineous (eg cousins married to each other)
Men with infertility suspected or due to congenital absence of the vas deferens

Offer referral for genetic counselling and carrier testing (III, B) 2–5 

If patient is pregnant, contact genetic services to organise screening in first trimester

Test couple for carrier status if planning pregnancy or in first trimester

Down syndrome

All pregnant women

Combined maternal serum and ultrasound screening in first trimester* 3, 6–11 

Maternal serum screening in second trimester† (C) 

Non-invasive prenatal test (NIPT)‡

Combined maternal serum and ultrasound screening in first trimester* 3, 6–11 

Maternal serum screening in second trimester† (C) 

Non-invasive prenatal test (NIPT)‡

Significantly increased probability:
Women who had a previous Down syndrome pregnancy
Women with positive maternal serum screening/nuchal translucency ultrasound, NIPT in first trimester or maternal serum screening in second trimester
Parent with a chromosomal rearrangement (eg balanced translocation of chromosome 21)

Fetal diagnostic genetic testing (C) 10 

Offer referral for genetic counselling

First or second trimester


Fragile X syndrome

Increased probability 

Children or adults of either sex with one or more of the following features:

  • developmental delay including intellectual disability of unknown cause
  • autistic-like features
  • attention deficit hyperactivity disorder (ADHD)
  • speech and language problems
  • social and emotional problems, such as aggression or shyness
  • relative with a fragile X mutation
  • a female with a history of primary ovarian insufficiency or premature menopause (aged <40 years) 14–16
  • adults with ataxia, balance problems and parkinsonism

Deoxyribonucleic acid (DNA) test for fragile X and karyotype/comparative genomic hybridisation by microarray for other possible causes of developmental delay 3, 12, 13 

Refer to genetic services for genetic counselling and testing at-risk family (I, A)

(IV, B)

Any age for diagnosis 

Prior to pregnancy to ascertain carrier status and reproductive risk

Haemoglobinopathies and thalassaemias

Increased probability
People from any of the following ethnic backgrounds:
Southern European, African, Middle Eastern, Chinese, Indian subcontinent, Central and South-east Asian, Pacific Islander, New Zealand Maori, South American, Caribbean, and some northern Western Australian and Northern Territory Aboriginal and Torres Strait Islander communities

Test for mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and ferritin 3,18–20 

Haemoglobin electrophoresis (III, B) 

Blood for deoxyribonucleic acid (DNA) studies 

Arrange partner testing if: MCV ≤80 fL and/or MCH ≤27 pg and/or abnormal haemoglobin (Hb) electrophoresis

Test couple for carrier status prior to pregnancy or in first trimester

Breast and ovarian cancer

Refer to Section 9.3. Breast cancer

Familial hypercholesterolaemia (FH)

Increased probability
Premature ischaemic heart disease (ie ischaemic heart disease in men aged <55 years and women aged <60 years)
First-degree relative with premature ischaemic heart disease (men aged <55 years and women aged <60 years)
Total cholesterol >7.5 mmol/L or low density lipoprotein-cholesterol (LDL-C) >4.9 mmol/L
First-degree relative with a total cholesterol >7.5 mmol/L or LDL-C >4.9 mmol/L
Tendon xanthomata or arcus cornealis at <45 years of age

Assess their probability of having FH using the Dutch Lipid Clinic Network (DLCN) criteria or Modified UK Simon Broome (MUKSB) criteria (III, B) (Appendix 2B. Dutch Lipid Clinic Network Criteria for making a diagnosis of Familial Hypercholestroloaemia in adults) 21, 22 

Offer referral to a lipid disorders clinic if DLCN score ≥3 or the MUKSB suggests possible FH

First presentation

Hereditary haemochromatosis (HHC)

Increased probability
All first-degree relatives of patients with HHC who are C282Y homozygous or C282Y/H63D compound heterozygous

Positive family history – asymptomatic and symptomatic 9,23–29 

For patients aged >18 years, test for HFE mutations, transferrin saturation and serum ferritin to simultaneously assess future and current risk of iron overload (C). Medicare Benefits Schedule (MBS) rebate applies if affected relative is first-degree relative; no MBS rebate applies for more distant relatives 

If HFE mutation tests show C282Y homozygous or C282Y/H63D compound heterozygous result, arrange for all of that patient’s first degree relatives aged >18 years to have tests for HFE mutations and transferrin saturation and serum ferritin (C). MBS rebate applies

Aged >18 years at first presentation 

Although abnormalities in transferrin saturation and serum ferritin may occur at <18 years of age in patients with HHC, morbidity from significant iron overload is exceedingly rare before the age of 18 years

Consider in these patients:
Patients with conditions that could be a complication of haemochromatosis (eg arthritis, chronic fatigue, erectile dysfunction, early menopause, cirrhosis, hepatocellular carcinoma, cardiomyopathy, diabetes mellitus)
Patients with liver disease of unknown cause, including those with suspected alcoholic liver disease
Patients with a family history of haemochromatosis, liver cancer, unexplained early death from liver or heart failure
Patients with porphyria cutanea tarda and chondrocalcinosis (‘pseudogout’)

Other patients – asymptomatic and symptomatic 

For patients aged >18 years, test transferrin saturation and serum ferritin 

If transferrin saturation >45% or serum ferritin >250 µg/L on repeated testing, test for HFEmutations. MBS rebate applies 

The ideal sample for testing transferrin saturation and serum ferritin is early morning fasting blood test with iron supplements withheld for 24 hours


*First trimester Down syndrome screening:

  • free beta human chorionic gonadotrophin (HCG), pregnancy associated plasma protein at 10–12 weeks (this also provides risk for trisomy 18 and Edwards syndrome)
  • nuchal translucency screen at 11 weeks, 3 days to 13 weeks, 6 days
  • NIPT‡ from 10 weeks for trisomy 21, 18 and 13; not available for MBS rebate. Tests for fetal DNA in maternal blood

†Second trimester serum screening:

  • beta HCG, unconjugated oestriol, alpha-fetoprotein and inhibin A, ideally at 15–17 weeks; also gives risk for Edward syndrome and neural tube defects (NTDs)

ADHD, attention deficit hyperactivity disorder; CF, cystic fibrosis; DLCN, Dutch Lipid Clinic Network; DNA, deoxyribonucleic acid; FH, familial hypercholesterolaemia; Hb, haemoglobin; HCG, human chorionic gonadotrophin; HHC, hereditary haemochromatosis; LDL-C, low density lipoprotein-cholesterol; MCH, mean corpuscular haemoglobin; MCV, mean corpuscular volume; MUKSB, Modified UK Simon Broome; NIPT, non-invasive prenatal test; NTD, neural tube defect


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