The rapid reduction in cost and increased integration of genomic tools into clinical practice, has led to a renewed interest in pre-conception carrier screening as seen in recent Progress Educational Trust events and the annual meeting of ESHRE in June. The UK Jewish population has had experience with pre-conception carrier screening for almost 30 years. Given this, we feel there is a benefit in sharing some of our experiences before the potential expansion to a larger population.
Tay-Sachs disease is a textbook example of how carrier screening can identify couples at risk of having children with an autosomal recessive disorder. Tay-Sachs disease is a rare and devastating inherited disorder that results in progressive neurological degeneration. Infants typically appear healthy until the age of 3-6 months, when they start to show developmental delay, seizures, paralysis and death in early childhood.
Tay-Sachs disease in the general population is very rare, but the prevalence of the disease is much higher in individuals of Ashkenazi (eastern and central European) Jewish descent.
Before the adoption of carrier screening in the 1970s, Tay-Sachs disease had a devastating impact on the Jewish communities of the USA and Canada, with up to 60 new cases diagnosed every year. In 1983, after watching four of his children die in infancy from Tay-Sachs disease, Yosef Ekstein established 'Dor Yeshorim', a not-for-profit organisation based in New York City, aimed at reducing Tay-Sachs disease in the strictly orthodox Jewish community of New York and other areas.
Dor Yeshorim is an innovative, premarital and anonymous carrier screening programme for fatal or debilitating genetic disorders. It provides participating individuals with a unique identification number that can be used to inform a prospective couple of 'genetic compatibility'. If both are carriers of the same disease, they are told that the match is incompatible, advised of the risks and offered genetic counselling. If neither or only one individual is a carrier, they are told they are compatible, and the carrier is not identified.
The programme has since expanded its carrier screening to nine disorders that are more prevalent within the Jewish population. The Dor Yeshorim screening system is aimed at the specific circumstances of the strictly orthodox Jewish community, where there is a tendency for parentally-arranged marriages, strong objections to prenatal diagnosis and pregnancy terminations, and a high risk of social stigmatisation of healthy carriers.
While many people would be uneasy with this model of carrier screening, it is clear that Dor Yeshorim has been remarkably successful. By 1993, the incidence of Tay-Sachs disease in the US and Canadian Jewish population had been reduced by more than 90 percent. The programme now screens around 25,000 individuals annually across 11 different countries and estimates that one in 100 prospective couples are both carriers of the same disease.
In the UK, the increased incidence of Tay-Sachs disease in the Ashkenazi Jewish population has meant that carrier testing has been freely available since 1999 through the NHS. A proviso of NHS carrier screening however is that individuals are free to decide for themselves whether to be tested and importantly, what happens with their results.
Carriers can choose to avoid other carriers or, if both partners are carriers, can opt for preimplantation genetic diagnosis (PGD), prenatal testing and termination of affected pregnancies. NHS testing provides an opportunity to screen for Tay-Sachs disease in individuals uncomfortable with the Dor Yeshorim screening system as well as for those who would prefer testing for a single gene rather than a larger panel of diseases.
More recently, a new charity called Jnetics was established in the UK. It aims to help prevent, diagnose and manage genetic disorders that disproportionally affect the Jewish population. Jnetics' approach to carrier screening differs significantly in several respects from the Dor Yeshorim screening system.
It is pluralistic and aimed at the whole Jewish community, irrespective of their level of religious observance. It is also available more widely for those with Jewish ancestry. Results of any genetic tests and carrier status are given directly to the patient. Advice, counselling and support are given in the context of the patient's personal beliefs rather than from a religious perspective.
Several options now exist in the UK to help individuals with Ashkenazi Jewish ancestry avoid the increased risk of having a child with a genetic disorder. These include specific Tay-Sachs carrier screening available through the NHS, a panel of nine genetic disorders using Jnetics services or opting to participate in the UK branch of Dor Yeshorim.
The choice will likely be a reflection of religious affiliation, religious observance and societal pressures, but also personal belief of what is thought to be an appropriate number of disorders to test for and how important it is to receive carrier status.
There are distinct advantages and disadvantages of each system and people often hold strong opinions. However, it is important to note that together, they have effectively eradicated Tay-Sachs disease from a religiously and geographically diverse Jewish population and significantly reduced the incidence of other Jewish genetic disorders.
As widespread carrier screening becomes technically and economically feasible, several ethical, social and legal challenges have come to light. Deciding whom to offer carrier screening to, how many and what genetic disorders to test for, as well as the most appropriate level of anonymity are all difficult questions. These are concerns that the Jewish community has grappled with and continues to debate. This article highlights some of the strengths and weaknesses of the various methods of carrier screening and we hope it provides a useful starting point for future discussions about carrier screening expansion.