Rita Vassena, scientific director of the Eugin Clinic in Barcelona, welcomes the genetic information which expanded carrier screening can provide but warns that careful counselling is needed to fulfil its opportunities.
The global prevalence of all single gene diseases at birth is approximately 1 in 100, and 2% of all couples are at an increased risk of having a newborn affected by a severe recessive disease. Although estimates are difficult to find, taken together, birth defects and genetic diseases may account for up to 12% of hospitalisations in pediatric wards.(1,2,3) Expanded carrier screening, or ECS, is the process of testing an individual for status as a carrier of several recessive monogenic diseases. It is typically carried out by next generation sequencing from a small sample of peripheral blood or even saliva, requires 2-3 weeks for processing, and can test upwards of 500 genes simultaneously and for the same cost as analysing a few genes individually.
While carrier screening per se is not at all new, and for certain diseases such as cystic fibrosis or Fragile X syndrome is recommended by several scientific societies for all couples wanting to conceive, the number of diseases tested in an ECS raises new issues and requires an informed discussion among all stakeholders.
On the one hand, one could argue that ECS is a new and improved form of preventive medicine, one where we can identify at-risk couples preconceptionally, offer genetic counselling, and, if desired, suggest a range of reproductive options to prevent the birth of a child affected by a severe disease. The inheritance mode of all diseases tested in these panels is recessive or X-linked, and in these cases family history is of relative use to identify those couples at risk; a mutated allele, in fact, can run through several generations in the same family before becoming apparent following a match with a partner carrying, by chance, a mutation in the same gene. Currently, most couples only realise that they are carriers of a recessive disease with the birth of an affected child. As these couples often seek PGT-M for their future reproductive plans (an actionable alternative to reduce their reproductive risk), the preventive (preconceptional) assessment of this risk should be at least on the table as an option.
There are however some questions that need addressing when discussing ECS. Test takers should be informed carefully about the kind of information that the test can and cannot provide. Thus, a test might detect reproductive risk and help lower it, but an assurance of a healthy pregnancy can never be provided, as mutations can occur de novo in the developing fetus; as a result, careful counselling to avoid any misplaced sense of security is in order.
Genetic counselling should also be offered to interpret the results of the test, not just, as one would imagine, to interpret a positive finding but also to contextualise a negative one. Moreover, test takers should be aware that the size of the panel will determine the chance of finding a mutation, as we all carry some mutation in some critical gene, but even the largest panel cannot uncover all that there is in our genome.
In the situation - which will become increasingly common in the coming years - in which only one partner in a couple has undergone the test, all efforts should be made to avoid genetic discrimination and stigmatisation, whereas an individual carrying certain mutations is made to feel inferior or even responsible for the couple's genetic well-being. This becomes particularly true in the case of third-party reproduction, where lack of genetic education might lead to a request for a 'genetically clean' donor, a request that is as unethical as it is impossible to fulfil. Everyone on the face of the planet, no-one excluded, carries a certain mutation load in their DNA, a mutation load that is in fact the very drive of our own evolution as a species, embedded in our history and necessary for our future. In fact, the calculated average carrier burden for the more frequent rare recessive diseases is 2.8, meaning that we each carry on average at least 2.8 mutations in genes that are causative of severe rare diseases.
Such requests, however, highlight the lack of genetic education among the general population and healthcare professionals, and the need to increase overall genetic awareness if we are to tackle the immediate technological opportunities of genetics for reproductive well-being.
1. See http://www.who.int/genomics/public/geneticdiseases/en/index2.html
2. Ropers HH. On the future of genetic risk assessment. J Community Genet 2012; 3: 229-236
3. Yoon PW, Olney RS, Khoury MJ, et al. Contribution of birth defects and genetic diseases to pediatric hospitalizations. A population-based study. Arch Pediat Adolesc Med 1997; 151: 1096-1103.