Types of population genetic screening programs

24.21 The genetic tests used in population genetic screening programs can detect:

• current conditions that have a genetic cause and may have an available treatment (screening for current conditions);

• the existence of a disorder before the onset of symptoms, or the existence of a genetic mutation that predisposes to a disorder (predictive screening); or

• carrier status for a genetic condition (carrier screening).

24.22 Each type of genetic screening test is discussed below, with reference to Australian examples.

Screening for current conditions—Newborn screening

24.23 Screening for current conditions can be used to detect conditions very early in life in circumstances where prompt treatment may be effective. Such screening may also be used to identify symptomatic individuals where the genetic cause of their symptoms has not yet been established.

24.24 Screening soon after birth, or during early childhood, has three major aims:

• to enable prompt detection of treatable genetic conditions;

• to detect inherited conditions, allowing parents to make reproductive decisions before having more offspring; and

• to clarify the causes of an infant or child’s condition.

24.25 In all States and Territories, newborns are screened for a number of genetic conditions, including phenylketonuria (PKU).^[18] Newborns affected by PKU are unable to break down the amino acid phenylalanine and, untreated, the disorder causes significant brain damage within months. Early detection allows newborns to be placed on a special diet that will prevent brain damage and ensure normal development.

24.26 The nature of the genetic conditions tested for in newborn screening programs is such that testing cannot be delayed until the child is older. The conditions require immediate medical or dietary intervention to preserve the life or health of the infant. All newborns are tested unless parents refuse consent. Parents are provided with leaflets and other information about the nature and value of the test for neonatal health and in practice consent is rarely refused.^[19] Tests are carried out by taking a small sample of blood via a heel-prick, and the blood is stored on blotting paper cards. A sample newborn screening card is reproduced at the end of this chapter.

24.27 Other screening programs detect current conditions for which there is limited treatment in order to confirm a diagnosis or to facilitate informed reproductive choice. For example, as noted above, all States conduct early childhood screening for Fragile X syndrome, targeting individuals with intellectual disabilities. The identification of a child with Fragile X is often followed by cascade screening of relatives^[20] and can help prevent families from bearing more children who will have the disorder.

24.28 Screening programs can also provide peace of mind to parents by clarifying the cause of a child’s condition. The symptoms of Duchenne muscular dystrophy (DMD), another genetic disorder with limited treatment options, are often not correctly diagnosed for some years.^[21] In relation to the possible benefits of screening for DMD, one parent of a child with DMD noted that, had she known the reason for his symptoms earlier:

I could have done more for him … We would never have labelled him lazy or a dreamer. We could have started steroid treatment and other therapies earlier and to the best advantage. More importantly, he could have had a name for his difference and understood the weakness he felt.^[22]

Carrier screening—Tay-Sachs disease

24.29 Carrier testing is used to detect individuals who carry a recessive gene that could be passed on to their children. As discussed in Chapter 2, if two carriers of a recessive gene have children, the child may receive copies of the defective gene from each parent and develop the genetic condition. For X-linked recessive conditions, male children who receive one copy of the defective gene may develop the condition.

24.30 Carriers generally do not suffer from the disorder caused by the genetic mutation they carry and thus are often unaware of their status and of the fact that they may pass a genetic condition on to their children. Carrier screening programs seek to alert individuals to their carrier status so that they are able to make informed decisions about reproduction. These may include choosing not to have children, having children through sperm or egg donation, adoption, or pre-implantation genetic diagnosis.

24.31 An example of selective carrier screening is a program that screens students at a number of private Jewish schools in Sydney for Tay-Sachs disease (TSD) carrier status. In the general population, only about one in 300 people are carriers for TSD, but in the Ashkenazi Jewish community the rate is closer to one in 30. TSD causes delayed development followed by neurodegeneration, blindness and eventually death, usually by the age of five.^[23]

24.32 Under the program, students are educated about the implications of carrier status and about the disease in general, and given the opportunity to take a voluntary screening test. The program employs a gene trustee who holds results until the student requests them.^[24] If a student elects to receive his or her test results, and the results are positive, the student is contacted by a genetic counsellor.^[25] The program aims to reduce the incidence of TSD within the Jewish community by enabling individuals to make more informed reproductive decisions.

24.33 The project also has research aims. The organisers collect and analyse data about the uptake of testing, the effect of educating participants about the condition, the psychosocial implications of screening, and participants’ reactions to test results.^[26]

24.34 Population genetic screening programs for carrier status, particularly those targeted at higher risk populations, have had considerable success in reducing the incidence of some genetic disorders. For example, a national screening program for carriers of β-thalassaemia in Sardinia has reduced the incidence of the disorder from one in 250 live births in 1974 to one in 4000 in 1996.^[27]

Predictive genetic screening—Haemochromatosis

24.35 Chapter 2 discussed the importance of penetrance, a measure of the likelihood that a person carrying a genetic mutation will develop the disease associated with it.^[28] Penetrance is relevant to population genetic screening because screening often targets asymptomatic individuals. From a health funding perspective, screening for only slightly penetrant genetic mutations may not be cost-effective because most individuals who are tested will not develop the disease. Also, if healthy people are offered genetic tests that may suggest they are predisposed to a disorder, this information should be accurate enough to enable them to take action, rather than merely creating doubt and anxiety.

24.36 Predictive genetic screening is mainly undertaken to inform a larger proportion of the community whether or not they have a condition or a predisposition to a condition, and this in turn may enable them to make health decisions that may slow or treat the condition. Predictive test results might also influence a participant’s reproductive decisions.

24.37 An example of population genetic screening for predisposition to disease is HaemScreen, a pilot genetic testing program conducted by the Murdoch Childrens Research Institute in a number of Melbourne workplaces.^[29] Participants agree to be tested for genetic predisposition to haemochromatosis, a condition that causes the body to accumulate excess iron leading to irreversible organ damage.^[30] Part of the rationale behind HaemScreen is to target a section of the population that is less likely to visit their doctor. Screened individuals who are found to be at risk of developing the condition may then take preventive measures, such as giving blood regularly.