The European Society
of Human Genetics

2021 Press Releases

The use of polygenic risk scores in pre-implantation genetic testing is unproven and unethical, says ESHG

Some private fertility clinics have begun to sell polygenic risk scores1 (PRSs) analyses on embryos to prospective parents.   This practice raises many concerns, says the European Society of Human Genetics in a paper published today (Friday 17 December) in the European Journal of Human Genetics*, since there is no evidence that PRSs can predict the likelihood of as-yet unborn children being liable to a specific disease in the future.

While it is quite normal for parents to consider any genetic risks they may pass to their children, this would usually be done by performing genetic testing for typical genetic conditions, such as Down syndrome or cystic fibrosis. In these cases, the disease has a single genetic cause and therefore the ability of the test to predict its development in any offspring is high.

“PRSs are a completely different matter. Many conditions are caused by a combination of genetics and environment, and PRSs are only able to capture parts of any of the relevant genetic component, which is itself likely to be highly complex and difficult to analyse.  In addition, while PRS may identify individuals at risk of a given disease in the general population (where the genetic variability is very wide) there is no evidence that they can be useful for a couple in determining the choice of one embryo over another, as the genetic variability within an individual family is limited,” says Dr Francesca Forzano, chair of the ESHG Public and Professional Policy Committee.

In addition, research on PRSs has been performed and is ongoing on liveborn, mostly adult, individuals, with the aim of deciphering the pathological mechanisms underlying complex multifactorial diseases.  No information on the value of PRSs to predict disease development in postnatal life is available for embryos. In fact such studies would be wellnigh impossible to perform in embryos, given that one might have to wait decades for the predicted disorder to appear - or not.

At present, performing a PRS test for embryo selection would be premature at best, say the authors Adequate, unbiased information on the risks and limitations of this practice should be provided to prospective parents and the public, and a societal debate must take place before any potential application of the technique in embryo selection.  Such a debate should be focused particularly on what would be considered acceptable regarding the selection of individual traits. Without proper public engagement and oversight, the practice of implementing PRS tests for embryo selection could easily lead to discrimination and the stigmatisation of certain conditions.

“It is also vital to provide prospective parents with a clear understanding of the difference between counselling and marketing,” says Professor Maurizio Genuardi, ESHG President. “And at a time when healthcare resources are under strain, it is important that the limited money available should be spent on tests that are known to be effective. Currently, research resources would be better spent on improving knowledge about how PRSs interact with the environment in which we live, rather on the premature application to our future children of an inadequately assessed test with potentially misleading results.”



1A polygenic risk score reflects an individual’s estimated genetic predisposition to a given disorder and can be used in predicting the likelihood of that individual developing the disorder

European Human Genetics Conference 2021

August 28-31, 2021, Virtual Meeting

Identification of the genetic causes of childhood epilepsy shows the way to improved treatment and care

Epilepsy is one of the most common chronic neurological diseases, affecting more than 50 million people worldwide. Although it is believed that a large proportion of childhood-onset epilepsies are caused by genetic changes, it remains unknown precisely how many of these patients suffer from a genetic disorder and how often the treatment can be targeted to their specific genetic alteration. Now, results from research to be presented at the annual conference of the European Society of Human Genetics today [Tuesday] have shown a genetic cause for their condition among half of those studied. This will not only aid in the prescription of appropriate, tailored, treatments, but also preclude the use of unnecessary diagnostic procedures, say the investigators.

Dr Allan Bayat, MD, a consultant in paediatric neurology at the Danish Epilepsy Centre, Dianalund, Denmark, and colleagues studied 290 children with a diagnosis of epilepsy or who presented with seizures accompanied by a high temperature that were either long, or in which consciousness was not regained between events (prolonged and clustering febrile seizures).  The children were born between 2006-2011 and followed at the centre in 2015.  After obtaining informed consent, the children underwent genetic testing. “We found a genetic cause in half of those tested and also that half of those again could receive a tailored treatment. We hope that drug companies and the scientific community will be able to produce new drugs or repurpose existing ones that may be being used to treat entirely unrelated conditions to improve precision treatment possibilities for those for whom this is currently not available,” says Dr Bayat.

In recent years, the number of genes known to be associated with epilepsies has risen to over 500, and gene panel testing and exome sequencing* are now routine analyses in many countries. Such testing is most important in children whose seizures commence when they are under three years of age, or with a family history of seizures, brain malformations, or cognitive comorbidities. However, in many parts of the world genetic testing is not systematically offered to such people, and there is often a long delay between the onset of symptoms and the test. Our results show that genetic testing is crucial in such patients in order that they may receive appropriate counselling and treatment,” Dr Bayat says.

An additional advantage of being able to identify a genetic cause is the avoidance of potentially harmful treatments. Genetic sequencing has shown that the majority of monogenic epilepsies, in which a single genetic change is involved, are caused by changes in ion channels, membrane proteins that are abundant in the central nervous system. While some genetic changes reduce the function of ion channels, others increase them. Most anti-epileptic drugs currently available target and block these ion channels, so treatment with them in patients with symptoms cased by genetic changes that have already suppressed ion channel function would most likely do more harm than good.

The researchers intend to continue their work with further study of those individuals where they were unable to find a genetic explanation for their epilepsy. “We will re-evaluate the dataset obtained from exome sequencing at regular intervals and perform additional genetic testing with a method that can detect genetic changes that may be missed by exome sequencing. And we hope to explore whether these patients have an accumulation of risk variants in genes or pathways associated with epilepsy when compared to those where a genetic cause has been uncovered, and to controls.

“Getting a genetic diagnosis is of great importance for the children and the families. It provides an explanation and certainty, and it enables a more targeted genetic counseling, including knowledge about the prognosis and recurrence risk. Furthermore, it allows the subject and families to enter gene specific networks of families with the same genetic condition,” Dr Bayat concludes.

Chair of the ESHG conference, Professor Alexandre Reymond, Director of the Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, said: “The field has made great progress in identifying causative mutations following the introduction of high-throughput sequencing in epilepsy patients. Despite the high occurrence of the disease and its high genetic heterogeneity with hundreds of associated genes, my colleagues can now suggest a tailor treatment to a quarter of their patients and counsel half of the families, a remarkable step forward for precision health.”


*Exome sequencing is a technique for sequencing all of the protein-coding regions of genes in a genome. It is a quicker and cheaper alternative to while genome sequencing.  

Abstract no: C25.6 Genetic testing and its impact on therapeutic decision making in childhood-onset epilepsies - a study in a tertiary referral centre

Researchers develop all-in-one test for the avoidance of de novo genetic disease in embryos

De novo variants (DNVs), genetic mutations that were not previously identifiable in the family history of one of two prospective parents, may cause disease in any children they have. Where a disease-causing DNV is present in one parent, the risk of passing it to a child can be as high as 50% and being able to identify healthy embryos for transfer to avoid an affected pregnancy is clearly a high priority. To achieve this goal, identification of the group of genes inherited from one parent (the haplotype) that is linked with the mutation is necessary to transfer only healthy embryos. Until now this has been a difficult process and can often involve multiple embryo biopsies, which in themselves carry a risk.  But a group of Belgian researchers have developed a new, one-stop method using DNA from the parents of the affected prospective parent (the embryo’s/child’s grandparents). They will present their findings to the annual conference of the European Society of Human Genetics today (Tuesday).

Dr Eftychia Dimitriadou, Head of the Reproductive Genetics Unit at the Centre for Human Genetics, Leuven University Hospital, Leuven, Belgium, and colleagues recruited 22 couples where one of the partners carried a DNV mutation causing a Mendelian disorder. A Mendelian disorder is normally, but not always, caused by alterations in a single gene. Current practice for pre-implantation genetic testing (PGT) embryo selection for such couples is complicated, says Dr Dimitriadou. “It involves targeting a specific gene, and therefore important genome-wide information is missing.”

The researchers decided to try to streamline the process by using long read sequencing (LRS), a technique that can read the sequence of very long fragments of DNA. A major advantage of LRS is that it is much more accurate in detecting copy number variants (CNVs), that is deletions or duplications of DNA fragments, and single nucleotide variants (SNVs), i.e., alterations in the sequence of a single DNA molecule, especially in regions where the same sections of DNA are repeated. Determining the existence of such variants has important implications for the diagnosis or prediction of genetic disease. Specifically, LRS enables the separate sequencing of the two copies of a DNA region or fragment (in the prospective parent carrying the de novo mutation), one inherited from each parent (the ‘grandparents’ of the embryo).

“This allows us to determine whether the disease-causing mutation is located on the maternal or paternal copy of the affected chromosome in patients with DNVs,” says Dr Dimitriadou. “Subsequently, we can perform a comprehensive analysis of embryos in a single test and transfer those that are unaffected - and all this in a single workflow. However, this is the best-case scenario. On the rare occasions when the two grandparents have the same SNP profiles, interpretation is even more challenging.”

In addition to detecting dominantly inherited disease, where a single copy of the disease-associated mutation is sufficient to cause disease, the test is also able to detect embryos with a genome-wide abnormal number of chromosomes (aneuploidies). However, a comprehensive test does not mean that it is possible to detect every single genetic abnormality.

The new test only came into clinical application recently, but of the 23 IVF/PGT cycles that have already taken place, 15 embryos were mutation-free, free of detectable genome-wide genetic abnormalities, and of adequate quality for transfer. Six pregnancies resulted, and three babies have been born.

“Because children born with a genetic disorder often have severe physical manifestation, it is understandable that their parents are frequently concerned by the risk of a child being affected with inherited disease, for example, neurofibromatosis1 or Alport syndrome2. For the parents, the discovery that one of them has the disease has already imposed a huge emotional burden, and so we are proud to have been able to bring new hope to affected families. Our work is a good example of what can be achieved by a patient-oriented, multidisciplinary academic team,” says Dr Dimitriadou.

“However, there is a cloud on the horizon. New, innovative, tests such as ours, ‘home-grown’ in our hospital, may be outlawed by the EU’s In Vitro Device Regulation (IVDR) due to come into force in May 2022. The IVDR threatens the development and use of in-house, laboratory-developed tests by banning their use if there is a commercially produced ‘equivalent’ on the market. But often the test deemed to be equivalent is not sufficiently precise. Prohibiting the usage of tests for rare diseases, or those that are performed infrequently and hence of little importance to the commercial sector, threatens the facility of laboratories to develop the new, specialised diagnostic tests that are required if we are to continue to best serve the interests of patients,” she will conclude.

Chair of the ESHG conference, Professor Alexandre Reymond, Director of the Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, said: “Reproductive medicine started out with the goal of allowing infertile couples to have children. Progress has been rapid in the 43 years since the birth of the first IVF baby, leading to many advances, including in prenatal diagnosis. Now, through long-read sequencing, it can take yet another step forward and help “genetically at risk” families in their desire to have unaffected offspring.”


1Neurofibromatosis is a genetic disorder affecting the formation and growth of nerve cells, that causes tumours to grow on nerves.

2Alport syndrome is a genetic condition involving kidney disease, hearing loss, and eye abnormalities. Affected patients lose kidney function progressively.

Abstract no: C26.2 Comprehensive PGT for patients with de novo pathogenic variants following single-molecule long read amplicon sequencing based haplotyping

Finish the course: new genetic understanding of lack of adherence to medication will aid in the identification of patients at risk

How strictly patients follow a prescribed drug treatment (drug adherence) is clearly important if the therapy is to have maximum effect. A number of things can affect adherence, including behavioural and socioeconomic factors, but to date there have been few investigations into the role played by genetics. Now, research to be presented at the annual conference of the European Society of Human Genetics today has thrown new light on the potential biological mechanisms that can affect adherence to treatment.

Mattia Cordioli, MSc, a PhD student at FIMM, the Institute for Molecular Medicine Finland, Helsinki, Finland, and colleagues examined data from the FinnGen1 study, from Finnish nationwide health registries, and the national drug purchase registry to try to uncover determinants of adherence across different medication groups. Using information on the date that the individual purchase was made, and the quantity purchased, they were able to define adherence by dividing the initial quantity by the number of days, with reference to the prescribed daily dose.

The researchers then carried out a genome-wide association study (GWAS)2 to see if genetic variants might help explain variation in adherence. “We used these results to see whether we could find a correlation between adherence and other traits that are controlled by multiple genes, rather than just one (polygenic traits). We found that a positive genetic correlation between adherence and other traits, for example, educational achievement, meant that individuals with a genetic predisposition for higher educational achievement tended to be more adherent. On the other hand, those with a genetic predisposition for risk-taking were less adherent to the medication schedule,’ says Mr Cordioli.

The researchers also found that, while a genetic predisposition for higher systolic blood pressure was correlated with increased adherence to blood pressure medication, there was no such association in patients with such a predisposition for higher LDL (bad) cholesterol and statin adherence. “This is interesting and may reflect the need for better feedback on the action and efficacy of a particular medication in order to improve adherence,” says Mr Cordioli. Drug adherence was also positively correlated in patients with a genetic predisposition for type 2 diabetes and higher body mass index, suggesting that patients in higher risk categories tend to be more adherent.

Demographic and socioeconomic factors remain important, though they are probably rather more related to access to treatment than compliance with a drug regime. But studying individual genetics can unveil possible biological mechanisms affecting adherence. Their sample size to date has not been large enough for them to look at medications that are less commonly prescribed to see whether specific biological factors are involved in adherence there, too, but the researchers suggest that it would be worthwhile to do so.

“Our research has shown that adherence pertains more to an individual’s predisposition to a particular behaviour rather than to underlying biological factors such as the adverse effects of a particular drug. We are hopeful that the identification of those patients who are less likely to adhere to drug therapy may encourage and facilitate the design of effective information campaigns directed at them,” Mr Cordioli says. 

“Along with the advances in genetic testing that can show how an individual responds to drugs and therefore allow the prescription of tailored treatment, we believe that further biological investigations into individual adherence may make a valuable contribution to the design of new standard clinical practice in the future”, he will conclude.

Chair of the ESHG conference, Professor Alexandre Reymond, Director of the Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, said: “Adherence to a prescribed treatment has not previously been looked at from a genetic point of view and finding that this is potentially more linked to behavior than to adverse effects gives us clues on where the health system should put its efforts to gets the best results.”


1The FinnGen project was launched in 2017 with the aim of producing a data resource with genome data of 500,000 biobank sample donors in Finland (about 10% of the population) over six years with the aim of improving health through genetic research.

2GWAS are observational studies of a genome-wide set of genetics variants in individuals to see if any variant is associated with a trait. Such studies compare the DNA of participants with varying phenotypes (observable characteristics) for a particular trait or disease.

Abstract no: C17.5 Genetic and environmental determinants of drug adherence and drug purchasing behaviour.

Genetic data privacy, the GDPR, and research needs: a delicate balance

The EU’s General Data Protection Regulation (GDPR) has created a great deal of uncertainty about how key requirements should be interpreted. This means that collaborators in international genetic research projects do not always agree on fundamental issues such as whether they are processing personal data, consent requirements under the GDPR and on what basis genetic data can be transferred outside the EU/EEA, if at all.  These results from a study carried out by Colin Mitchell, Senior Policy Analyst in Law, Regulation and Digital Health, and colleagues from the PHG Foundation, University of Cambridge, UK will be presented to the annual conference of the European Society of Human Genetics today (Monday).

The investigators carried out legal research, interviews, and held an expert meeting to investigate the subject. They were supported by the UK Information Commissioner’s Office, responsible for national data protection. “This topic is of great concern to scientists and people working in genetic medicine because of the way that the GDPR made significant changes to the way that personal data from patients or research participants may be used,” says Dr Mitchell. “These changes are not specific to genetic data, but because such data are highly sensitive, their impact on the genetics field is considerable.”

Their analysis demonstrates that a range of legal interpretations are possible, and that other parts of the regulation, like those setting out ‘data subject rights’, are also potentially ambiguous in the genetic context. For example, interpreting the ‘right to access’ data in the genomic context will be complicated because multiple individuals or family members might be able to claim the data as their own.

Another problem is how to characterise ‘personal data’ (those data that can be used to identify an individual), as opposed to data that cannot be used in this way. The GDPR requires that a risk assessment be undertaken to see what sources of information could lead to identification. In the genomic context, finding agreement on this can be particularly challenging. And now, recent developments such as the growth of ancestry websites can complicate things further.

In the UK, Brexit is another new difficulty. The UK is a leader in genomic healthcare and research, and it is vital that collaboration with individuals and institutions in the EU/EEA should continue, say the researchers. “The UK is now a ‘third country’ and therefore subject to strict rules about receiving data from the EU. Now, the UK’s rules are almost identical to the GDPR. But should they diverge in the future due to changes on either side, this will pose a major problem,” says Dr. Mitchell.

Having identified the challenges associated with the GDPR and its impacts, the researchers looked into measures that could reduce these. “We believe that it will be possible to pursue a more genetics-sensitive approach with the regulators,” Dr Mitchell says. “And the GDPR also contains some mechanisms that could allow the genomics community to develop best practice for compliance with the regulation and set this out incodes of conduct or certification schemes to demonstrate compliance with the law. Developing such a system will not be easy, but it is crucial if confusion about data protection law is not to act as an unwarranted barrier to data sharing and scientific progress in genetics.”

Because of the high potential sensitivity and identifiability of genomic data, it is crucial that the correct balance between individual privacy and genomic science and medicine is struck. Getting this right is essential to avoid a breakdown in trust between the public and professionals that could lead to considerable, long-lasting harm to healthcare and scientific research.

The GDPR may have brought this issue into sharper focus, but it is not a new problem. “We were surprised to find that some of the major challenges and uncertainties related to legal standards that already existed in previous EU law. What has changed, though, is how these may need to be interpreted and how that interpretation now should be uniform across the whole EU/EEA. True coordination of the interpretation of the GDPR for genetic data across all the Member States will take time, and may be very difficult in practice”, says Dr Mitchell. “Though to some this may appear to be a somewhat technical and esoteric issue, it is absolutely essential to get it right if we are to continue to exploit the enormous potential of genetic medicine to the best of our ability.”

Chair of the ESHG conference, Professor Alexandre Reymond, Director of the Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, said: “Choosing between an individual’s privacy and the responsibility of a nation regarding the health of its citizens that can only progress with the exchange of increasing amounts of data has become more and more difficult. Legal standards are not adapted to the fast pace of technological change in genetics. Society as a whole will need to decide where the balance should be.”


The research was funded by the UK Information Commissioner’s Office as part of their innovation grant scheme.

Abstract no: PL2.6 The impact of the GDPR on genomic medicine and research

Genetic risk scores can aid accurate diagnosis of epilepsy

Although epilepsy is a relatively common condition, affecting approximately 1% of individuals worldwide, it is often difficult to diagnose in clinical practice, and it is estimated that up to a quarter of all cases may be misdiagnosed initially. Epilepsy is often inherited, and recent research has shown that sufferers have elevated polygenic risk scores1 (PRSs) for the condition. Now, investigators from Finland have proposed that PRSs could be used as a tool to help diagnose epilepsy in those individuals who have had a single seizure and distinguish them from those where the seizure has another cause. The results will be presented at the annual conference of the European Society of Human Genetics today [Sunday].

Together with other colleagues at the Institute for Molecular Medicine (FIMM), Helsinki, Finland, Henrike Heyne, MD (now working at the Hasso Plattner Institute, Potsdam, Germany) extracted data on 9660 individuals with epilepsy-related diagnoses from the over 269K people included in the FinnGen2 project and looked at their polygenic risk scores as compared to those of health controls. As expected, the individuals with epilepsy had a higher polygenic risk for the condition.

“In FinnGen we could also investigate the health records of participants who had suffered convulsions where the cause was unclear. Although some of them had later received a specific diagnosis of epilepsy, the majority had not. And we found that the genetic risk for epilepsy was significantly higher in individuals who received a specific epilepsy diagnosis than in those with only one seizure where the case was unclear,” says Dr Heyne.

Participants in the study ranged in age from a few months to over 90. In those under 40, the researchers found that the influence of the genetic factors was larger than in older individuals. This genetic influence was particularly high in those with adolescent myoclonic epilepsy, the type that made up the largest proportion of cases in the international epilepsy consortium used to identify which genetic variants convey highest risk to epilepsy. Although the sample size was relatively small, the results clearly showed the potential for the use of PRSs in the diagnosis of epilepsy, and the researchers hope to see them replicated in further studies with the larger sample sizes that are more usual in other common diseases such as high blood pressure or diabetes.

“Genetic risk could serve in future as a biomarker for epilepsy,” says Dr Heyne. “This could prove to be a very useful addition to existing methods, such as electroencephalograms. PRSs have been shown to be useful in many other diseases and it is likely that in the future their use may become standard practice, meaning that genetic data could help to make an epilepsy diagnosis immediately after a seizure.

Chair of the ESHG conference, Professor Alexandre Reymond, Director of the Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, said: “Genetic information often tells us whether a person is at increased risk to develop a disorder or not. In this study, the authors have pioneered the use of a genetic risk score to identify people at risk for epilepsy. Combining genetic data with other more traditional methods such as electroencephalograms could help identification of epileptic individuals, potentially allowing early treatment. Of note is that about 25% of epilepsy patients are under an effective regimen.”


1A polygenic risk score reflects an individual’s estimated genetic predisposition to a given trait or disorder and can be used as a predictive tool.

2The FinnGen project was launched in 2017 with the aim of collecting biological samples from 500,000 participants in Finland (about 10% of the population) over six years with the aim of improving health through genetic research.

Abstract no: PL2.6 Epilepsy polygenic risk scores in > 269k individuals with and without epilepsy

Dried blood spots from newborn screening can help identify the cause of sudden cardiac death in the young

The underlying cause of sudden cardiac death (SCD) in a young person is often difficult to identify. A genetic analysis could provide more information in many cases, but blood samples are not collected routinely at the time of death, and DNA extracted from the tissues collected at autopsy is damaged because of the way they are fixed in formalin and paraffin-embedded. But finding the cause is vital if relatives who may carry the same genetic variant as the victim are to be screened. Now, for the first time, researchers in Sweden have been able to carry out molecular autopsies for SCD nationwide, using dried blood spots (DBS) collected up to 40 years ago as part of the routine screening of newborn babies. Their findings will be presented at the annual conference of the European Society of Human Genetics today (Saturday).

Dr Angelica Delgado-Vega, MD, a specialist in Clinical Genetics at Uppsala University Hospital, Uppsala, Sweden, and colleagues from Uppsala and Gothemburg, identified all 22 Swedish cases of SCD between 2000 and 2010 in people aged under 35 with a post-mortem diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), an inherited disease of the heart muscle that affects approximately 1 in 1000 to 1 in 5000 individuals. Using whole exome sequencing1, they extracted DNA from DBS, post-mortem formalin-fixed paraffin-embedded (FFPE) heart tissue, and frozen blood samples of victims, where they existed.

Although the researchers found a lower yield of DNA from DBS compared with FFPE, all of the DBS samples passed quality control, compared to 62.5% of the FFPE samples. The quality of the results from DBS were similar to those from the frozen blood samples, and analysis showed clinically relevant genetic variants in 12 out of 19 families. “Four were located in ARVC genes and six in another gene known for causing an arrhythmic syndrome,” says Dr Delgado-Vega. “Additionally, we identified one case with hemochromatosis, an iron overload disorder, and one with myotonic dystrophy, a disorder of muscle function. Not only did this show us that molecular autopsy of DBS gave a reliable result in ARVC, but also allowed us to identify relatives who might be at risk of other disorders. We were pleased to find that the quality of the sequence data from such small amounts of DNA was better than we expected.”

The researchers now intend to offer carrier testing to these relatives and follow them clinically. They will also apply the DBS molecular autopsy technique in a larger group of 903 SCD victims from SUDDY, the Swedish Sudden Cardiac Death of the Young cohort. Even though their first results are impressive, this has not been a simple task, they say.

“It has been difficult to obtain the samples from the biobanks even though we have ethical permissions and consent from the relatives, due to logistic and internal regulations specific to each of them. The Swedish Board of Forensic Medicine, for example, has not provided any sample due to legal regulations,” says Dr Delgado-Vega. “Even though the results from FFPE samples had lower quality than those from DBS it still works in them. The acquisition of FFPE samples is also important because DBS are only available from 1976, when newborn screening started in Sweden.”

The sudden and often unexplained death of a young person is a devastating event for their families.

Through the identification of disease-causing variants, health systems can offer them an explanation. “And the identification of relatives who are carriers and thus at risk of sudden cardiac death means that we can offer them treatment and other preventive measures, because this is a preventable outcome. Tragically, however, many of our families have already lost several members to SCD,” Dr Delgado-Vega says.

“As this is a postmortem study, we cannot be totally sure whether the arrhythmogenic syndromes identified were a contributing cause of death or an alternative diagnosis or an overlapping phenotype. However, our findings provide valuable new knowledge about the biology of cardiomyopathies, where overlapping genes and phenotypes are common. We are evaluating each family individually. In several cases there are relatives diagnosed with the arrhythmogenic syndrome identified without evidence of ARVC. We hope that our findings will enable better risk assessment and care in these cases,” she will conclude.

Chair of the ESHG conference, Professor Alexandre Reymond, Director of the Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, said: “Arrhythmogenic syndromes are “sneaky killers” and it would seem to be common sense to try to identify individuals at risk as early as possible.  This is a typical example where an established practice, i.e. routine screening of newborn babies via dried blood spots, could and should be modernised in the years to come to assess more genes for the greater good.”


The research was funded by grants from Marcus Borgström, the Swedish Society of Medicine, Uppsala University Hospital, and Uppsala University Hospital, and Uppsala University, Sweden.

1Exome sequencing is a technique for sequencing all of the protein-coding regions of genes in a genome. It is a quicker and cheaper alternative to whole genome sequencing

Abstract no: C02.1 Sudden cardiac death due to ARVC in the young: molecular autopsy by whole exome sequencing of DNA from dried blood spots (DBS) collected at birth.