Genomics in general practice

Disease specific topics

Cystic fibrosis

Cystic fibrosis


Newborn screening will identify 85–90% of individuals with cystic fibrosis (CF), but will not identify individuals homozygous/compound heterozygous for rare CFTR (cystic fibrosis transmembrane conductance regulator) variants. Such patients may present to the general practitioner symptomatically (GP) symptomatically.

What do I need to know?

CF is the most common childhood onset life threatening genetic condition in Australia. CF primarily affects the lungs and digestive system, which become obstructed with excessive, thick mucus. It is a condition that follows an autosomal recessive inheritance Autosomal recessive conditions affect either sex, and often occur in the absence of any family history. Recessive conditions or traits appear when an individual inherits two copies of pathogenic variants in the same gene (one from each parent). Parents of a child with an autosomal recessive condition are usually asymptomatic carriers. The affected child has two copies of the particular gene change. The recurrence risk of autosomal recessive conditions is one in four for each pregnancy. Wide variability in clinical expression is common in many autosomal recessive conditions. Autosomal recessive conditions are more common when the parents are consanguineous. pattern, meaning both parents must carry a CF-causing gene variant Gene variants are small DNA sequence changes (ie additions, duplications, deletions, substitutions). These variants can have a range of effects: some may cause disease (pathogenic variant), while others do not cause disease but may modify an individual’s risk of disease (i.e may increase risk or provide a protective effect). The vast majority of gene variants are benign and do not result in disease but rather contribute to the differences between people. to be at risk of having a child with the disease.

About one in 25 Australians of northern European ancestry are carriers Recessive genetic conditions such as cystic fibrosis (CF) occur when a person inherits a particular genetic variant from each parent. A carrier is an individual who only has one copy of the gene variant and generally does not have symptoms, but can pass the variant to their children. Some conditions are due to a pathogenic variant in a gene on the X chromosome (X-linked inheritance). Typically, these conditions affect more males (who have the sex chromosomes XY) than females (who have the sex chromosomes XX). A woman who is a carrier of an X-linked condition has the variation on one of her X chromosomes, which she can pass on to her children. However, if the biological male has a pathogenic variant in an X chromosome gene, he will not pass it to his sons, but will pass it to all of his daughters. of a CFTR pathogenic variant. The most common variant in the CFTR gene is the p.Phe508del variant, which accounts for approximately 70% of all CFTR pathogenic variants in those of northern European ancestry. While there are more than 2000 variants in the CFTR gene, most of which are benign or of uncertain significance, around 40 pathogenic variants cause approximately 90% of CF in Australia.

Genetic testing

Almost all babies in Australia are screened at birth for CF. There are some who may be lost to follow up or refuse to consent for screening. Exact numbers in Australia are not available. Refer to ‘Newborn screening’ for more information.

Carrier screening Carrier screening is a test to determine whether an individual carries a genetic variant that does not generally affect that individual’s health, but increases his or her chance of having children with the condition in question. The outcome of such testing can influence future reproductive decisions. Carrier screening is performed on individuals who are not necessarily known to be at increased risk for a particular genetic condition. Screening tests can be conducted on individuals from specific groups such as those from a common ethnic background (eg: screening for Tay-Sachs disease carrier status in the Ashkenazi Jewish community) or entire populations. for CF can be offered by GPs to all couples planning a pregnancy (or already pregnant), regardless of family history or ethnicity. Refer to ‘Reproductive carrier screening’ for more information.

When should I refer?

Couples who are CF carriers should be referred for genetic counselling if they are planning a pregnancy or are in the first trimester of pregnancy.

Children suspected of having CF (who have not been previously identified through newborn screening tests) should be referred to a respiratory paediatrician for a sweat test. Symptoms may include recurrent cough, failure to thrive, lower respiratory tract infections, bronchiectasis and/or rectal prolapse.

Males presenting with infertility due to congenital bilateral absence of the vas deferens (CBAVD) may have an atypical form of CF. These men should be referred to a fertility specialist.

Other considerations

Cascade screening Cascade screening involves testing the close biological relatives of an individual who has or is a carrier of a genetic condition in order to determine whether these relatives carry the genetic variant or chromosomal alternation (thereby increasing their chances of developing the condition or having a child with the condition). For example, cascade testing is available under the Medicare Benefits Schedule for genetic testing for familial hypercholesterolaemia. should be offered following a diagnosis of CF or of a CFTR pathogenic variant carrier in a family to identify other carriers.

Further reading

This event attracts CPD points and can be self recorded

Did you know you can now log your CPD with a click of a button?

Create Quick log