Accessibility, availability and common practices regarding genetic testing for epilepsy across Europe: A survey of the European Reference Network EpiCARE

Abstract

Objective

The increasingly rapid pace of advancement in genetic testing may lead to inequalities in technical and human resources with a negative impact on optimal epilepsy clinical practice. In this view, the European Reference Network (ERN) for Rare and Complex Epilepsies EpiCARE conducted a survey addressing several aspects of accessibility, availability, costs, and standard practices on genetic testing across ERN EpiCARE centers.

Methods

An online Google form was sent to 70 representatives of ERN EpiCARE centers. Descriptive statistics and qualitative analysis were used for data presentation.

Results

We received 45 responses (1/center) representing 23 European countries with a better representation of Western Europe. Forty‐five percent of the centers did not have access to all available types of genetic testing, mainly reflecting the limited availability of whole‐genome sequencing (WGS). Thirty‐five percent of centers report cost coverage only for some of the available tests, while costs per test varied significantly (interquartile range IQR ranging from 150 to 1173 euros per test across centers). Urgent genetic testing is available in 71.7% of countries (time‐to‐urgent result: 2 day to 2 months). The average time‐to‐result of specific tests in case of non‐urgent prescription has a significant variance across centers, with the biggest range observed for whole‐exome sequencing (6–128 weeks, IQR: 27 weeks). The percentage of agreement among the experts regarding the choice of genetic test at first intention in specific clinical situations was in all cases less than 50 percent (34.9% to 47% according to the proposed scenarios).

Significance

Costs, time to deliver the results to the clinician, and type of first‐line genetic testing vary widely across Europe, even in countries where ERN EpiCARE centers are present. Increased availability of genetic tests and guidance for optimal test choices in epilepsy remains essential to avoid diagnostic delays and excess health costs.

Plain Language Summary

The survey of the ERN EpiCARE highlights disparities in genetic testing for epilepsy across 45 ERN EpiCARE centers in 23 European countries. The findings reveal variable access to certain genetic tests, with lowest access to WGS. Costs and time‐to‐results vary widely. Urgent genetic testing is available in 71.7% of countries. Agreement among experts on first‐line genetic tests for specific patient scenarios is below 50%. The study emphasizes the need for improved test availability and guidance to avoid diagnostic delays and unnecessary costs. EpiCARE has the mission to contribute in homogenizing best practices across Europe.

Key points.

• Urgent genetic testing accessibility could be improved, as it is not available in around 1/3 of the centers.

• Costs and time to deliver the results to the clinician are highly heterogeneous.

• There is a fundamental need for harmonization of the availability and the common practices of genetic testing for epilepsy in Europe.

• The European Reference Networks (ERNs) and the national authorities should continue to collaborate toward standardization and optimal care of persons with epilepsy of genetic etiology.

• Access to genetic testing for epilepsy across Europe is variable with the lowest access to whole‐genome sequencing (available in only 60% of ERN EpiCARE centers).

1. INTRODUCTION

Epilepsy represents an important part of the global burden of neurological disorders. ¹ The 73rd World Health Assembly of Word Health Organization (November 2020) ² recognized that “epilepsy and other neurological disorders are the leading cause of disability‐adjusted life years and the second leading cause of death worldwide” and “that epilepsy is one of the most common neurological disorders globally affecting an estimated 50 million people worldwide.” Genetic alterations are a major cause of epilepsies, with recent data on their epidemiology suggesting that monogenic epilepsies may account for one per 9970 to one per 24 300 live births. ³ Many of these genetic etiologies remained undiagnosed or were diagnosed with a delay of several years. ⁴ The advances in epilepsy genetics and next‐generation sequencing (NGS) over the past two decades have led to the discovery of hundreds of new genes and pathogenic variants and to the emerging of targeted therapies. ⁵ , ⁶

This new genomic era in epilepsy and other neurological disorders comes along with an increased interest in an earlier identification of genetic etiologies and several challenges to the clinicians. ⁷ For example, the clinicians need to stay updated regarding the continuously expanding phenotypical spectrum of specific monogenic epilepsies on the one hand and the overlapping of similar phenotypes related to different genes on the other. ⁸ , ⁹ A UK study has shown that, in patients with early‐onset seizures and severe developmental delay diagnosed by a gene panel, the clinician had sufficient certainty of specifying a causative gene in only 15% of cases before the genetic testing was performed. ¹⁰ In case of a suspected genetic etiology in epilepsy, an accurate phenotype–genotype correlation is very important and can significantly increase the diagnostic yield of the performed test. ¹¹

Another challenge of the genomic era lies on the criteria for selection of patients and appropriate genetic testing as well as on the interpretation of the genetic results. The availability of several new (whole‐genome sequencing [WGS], whole‐exome sequencing [WES], clinical exome sequencing [CES], customized gene panel—differences between the aforementioned tests detailed in Appendix S1) and older genetic tests (karyotype, fluorescence in situ hybridization [FISH], array—comparative genomic hybridization [CGH]) and the growing numbers of variants of unknown significance, along with the great phenotypic and genetic heterogeneity in epilepsy, further complicates this process. ¹² In specialized centers, the genetic issues mentioned above may be addressed with specific protocols (national or local) or discussion in multidisciplinary meetings, involving geneticists, adult and/or child neurologists, epileptologists, neurophysiologists, neuropsychologists, neuroradiologists, and others. ⁸ , ¹³ The lack of decision support tools for clinicians may result in varied practices not only between countries, but also within the same country, and in significant diagnostic delays and inappropriate management strategies. The practices regarding genetic testing could further be influenced by test availability, accessibility, and related costs. The former hypotheses were further supported by experience sharing within the working groups of the European reference network (ERN) for rare and complex epilepsies, EpiCARE.

According to the Directive 2011/24/EU on the application of patient's rights in cross‐border healthcare, ¹⁴ two of the main objectives of the ERNs are: “to facilitate improvements in diagnosis and the delivery of high‐quality, accessible and cost‐effective healthcare for all patients with a medical condition requiring a particular concentration of expertise in medical domains where expertise is rare” and “to maximize the cost‐effective use of resources by concentrating them where appropriate.”

In this view, the EpiCARE network has created a survey regarding the provision of genetic tests for epilepsy across Europe. The survey's secondary aim was to investigate prevalent practices of physicians related to the decision of whether to perform genetic testing and the choice of the genetic tests based on the epileptic phenotype.

2. METHODS

2.1. The EpiCARE network

The ERN EpiCARE for rare and complex epilepsies was launched in 2017 as part of the 24 ERNs labeled by the European Commission. One of the network's main objectives is to facilitate the accessibility of detailed diagnostics to individuals of all ages with rare and complex epilepsies across Europe with the ultimate goal of improving interventions and outcomes. Today, the ERN EpiCARE is composed by 60 medical teams accredited by the European Commission as centers of the network and 10 collaborating EpiCARE partners, all highly specialized epilepsy health centers, located in 29 European countries. The core program of the network involves several clinical, research, and educational projects organized and developed under the umbrella of 20 different work groups (WGs) (https://epi‐care.eu) and a close collaboration with a patient advocates group.

2.2. The survey

This survey was conceived and initiated by members of ‘WG14 Education and training’ funded under the “Development of a simplified interactive decision‐making process tool regarding genetic epilepsies” project (CEF 2020). During the development of the tool, the literature review and the discussion among the group members have led to the hypothesis that there are considerable variations in common practices and significant inequalities in the provision of genetic testing across European countries. Therefore, we created a survey for distribution to the network centers to better address the needs and expectations of the target audience.

The survey items were discussed and decided upon by the members of the multidisciplinary working group, including child and adult neurologists, epileptologists, and geneticists. A consensus on the final form of the survey was achieved during an online meeting after an initial round of review. The final version is available in Appendix S2. The survey was then implemented into a Google Survey form, and electronic invitations to complete the online forms were sent to 70 participants, all representatives of the accredited ERN EpiCARE centers and the collaborating partners of EpiCARE, present in 29 European countries. The survey could be filled out by the representatives themselves or by any other experienced member of the tertiary reference EpiCARE center. The list of participating centers is available in Appendix S3.

The invitations with the survey link included a text regarding the aim of the survey, the usage of the results, and the confidentiality of the respondents' individual information. The survey was open for approximately 1 month, with regular reminders for completion.

2.3. Data analysis

Data were exported directly in a Microsoft Excel file from the Google survey editing platform.

The countries that responded to the survey were further categorized into four regions (Western, Southern, Eastern, and Central Europe) according to the grouping used by the European Study on the Burden and Care of Epilepsy (ESBACE, www.esbace.eu) and relevant publications ¹⁵ (Table 1).

TABLE 1.

Number of centers (N = 45) that responded to the survey per country and per European region (according to the division of regions used by the European Study on the Burden and Care of Epilepsy, ESBACE, www.esbace.eu ¹⁵ ).

Western Europe country, no. of centers per country	Southern Europe country, no. of centers per country	Central Europe country, no. of centers per country	Eastern Europe country, no. of centers per country
Austria (N = 2)	Greece (N = 2)	Czech Republic (N = 1)	Croatia (N = 2)
Belgium (N = 2)	Italy (N = 8)	Hungary (N = 1)	Estonia (N = 2)
Denmark (N = 1)	Portugal (N = 2)	Poland (N = 1)	Latvia (N = 1)
Finland (N = 1)	Spain (N = 3)	Slovenia (N = 1)	Romania (N = 1)
France (N = 5)
Germany (N = 4)
Ireland (N = 1)
Netherlands (N = 1)
Norway (N = 1)
Sweden (N = 1)
United Kingdom (N = 1)
Total: 20	15	4	6

We further analyzed the results using SPSS 21.0. Descriptive statistics with the presentation of the percentages were used for the single‐choice answers, while frequencies of each response were presented for the multiple‐choice answers of the questionnaire. Chi‐square Pearson test for independence (with Monte Carlo correction when appropriate) was performed to test correlations between the respondent's answers and the main country/region of practice, when appropriate.

The data of specific open questions regarding time‐to‐result and to costs of genetic testing were sometimes provided by the respondents as a range instead of an approximate estimation. In that case, the upper limit was considered with regard to the time‐to‐result for urgent genetic testing. The median and the interquartile range (IQR) were calculated for the costs and the time‐to‐result of other genetic tests.

Finally, qualitative data analysis was used to present the respondent's answers to open questions and additional comments at the end of the questionnaire.

3. RESULTS

We received 45 responses (one per center) present in 23 European countries. Most of the countries (N = 13) were represented by a single center; six countries were represented by two centers and only four countries were represented by more than two centers (Table 1). The most represented area was Western Europe (11/23).

The majority of the respondents were pediatric neurologists (44.4%), followed by child/adult epileptologists (26.7%), geneticists (13.3%), and adult neurologists (8.9%).

3.1. Accessibility

Fifty‐five percent of the centers had access to all available types of genetic testing from a list of older and more recent genetic tests (karyotype, molecular karyotype/array‐CGH, single‐gene sequencing, epilepsy gene panel, CES, WES, WGS, and other specific tests such as methylation‐sensitive multiplex ligation‐dependent probe analysis/MS‐MLPA, Fluorescence In Situ Hybridization/FISH, etc.). Forty percent of the centers did not have access to WGS; a few centers (8/45) did not perform CES, but almost all of them (7/8) had access to other next‐generation sequencing tests instead (WES/WGS/gene panels).

3.2. Availability

3.2.1. Trio‐sequencing

Trio‐sequencing was available when considered essential for genetic diagnosis in 80% of the centers. It was usually performed in the case of WES/WGS/CES, but almost 45% of the centers (16/36) would also offer trio‐sequencing for gene panel testing. Respondents' further comments referred to the fact that the segregation analysis was usually performed instead of trio‐WES or that the trio‐WES was used as a second step in order to interpret the genetic results of the index patient.

3.2.2. Genetic testing prescription

We have asked the clinicians who could officially prescribe genetic testing for an epileptic disorder in their countries of practice. The responses were distributed as follows: in 71.1% (32/45) of responses, any practitioner (geneticist, neurologist, pediatrician, epileptologist, neonatologist, etc.) involved in epilepsy care could prescribe genetic testing; in 8.9% (4/45) any practitioner, as long as specific clinical requirements (as specified by a data set/prescription sheet for each testing) were met; and in 6.7% (3/45) of responses, prescription was possible only by a geneticist or only upon official confirmation of the indication by a geneticist. Other (6/45) answers included prescription only by geneticists or pediatric/adult neurologists and variability of prescription requirements according to the test, the area of practice even within the same country, and the health insurance coverage.

3.2.3. Costs

Full insurance cost coverage was available in 64.4% of the responding centers.

Thirty‐five percent of centers (in 16/45 centers; 11/23 countries) reported cost coverage only for some of the available tests. Among the answers regarding the type of test not (fully) reimbursed (N = 14), the most common answers were WES (9/14), WGS (9/14), and gene panel (3/14). The two Greek centers have reported insurance coverage only for the karyotype and single‐gene testing (MECP2, SCN1A, 15q deletion, etc.), while the Hungarian center reported seldom case‐by‐case coverage of gene panel following a specific application to the insurance. In some cases, the cost coverage was different even within the same country, with full genetic cost coverage in some regions and only partial in others (full coverage in 1/4 centers in Germany, 1/3 centers in Spain, 7/8 centers in Italy, and ½ centers in Austria). Some centers (4/14) covered (part of) the costs via research or hospital funding. Figure 1A provides further details on genetic cost coverage across countries.

FIGURE 1.

Map representing the availability of (A) cost coverage of genetic testing and (B) urgent genetic testing across European centers.

We have also investigated the average cost per test across centers, in case the families had to cover the costs of genetic testing without being reimbursed. The costs were higher for the most recently developed tests, but there is a big variance of costs across countries. For example, the median cost of a gene panel is 800 euros with a minimum cost of 300 euros and a maximum cost of 3000 euros. The median cost (in euros), the variance, and the IQR of costs per test are presented in Table 2.

TABLE 2.

Representation of median costs and time‐to‐result for the most common genetic tests.

Test (N1, N2)	Cost; median (min‐max, IQR)	Time‐to‐result; median (min‐max, IQR)
	Euros	Weeks
Karyotype (8, 39)	163 (80–1200, 155)	4 (1–14, 2.5)
Array‐CGH (10, 43)	550 (150–1200, 605)	8 (2–14, 6)
Single mutation (10, 35)	153 (50–300, 150)	4 (1–34, 5.5)
Single‐gene NGS (9, 34)	400 (180–1625, 560)	8 (2–72, 10)
Gene panel (13, 41)	800 (300–3000, 325)	12 (4–52, 18)
CES (10, 34)	1225 (500–4500, 1173)	18 (4–65, 18.5)
WES (14, 40)	1312 (800–5250, 775)	24 (6–128, 27)
WGS (5, 22)	2000 (1500–2000, 250)	26 (5.7–76, 23.5)

Note: N1 = number of valid answers regarding costs; N2 = number of valid answers regarding time‐to‐result.

Abbreviations: CGH, comparative genomic hybridization; CES, clinical exome sequencing; IQR, interquartile range; NGS, next‐generation sequencing; WES, whole‐exome sequencing; WGS, whole‐genome sequencing.

3.2.4. Urgent genetic testing

The participants were asked whether in their countries of practice, any kind of genetic testing was available “urgently,” as per clinical evaluation. In case of positive answer, the type, the indication, and the time‐to‐result of the urgent genetic testing were further requested as a free text. The responses indicated availability of urgent genetic testing in 71.7% of the centers (not yet available in 1/5 centers in France, ¼ centers in Germany, 2/2 centers in Greece, 5/8 centers in Italy, 1/3 centers in Spain, 1/2 centers in Portugal, and 1/1 center in Romania) (Figure 1B).

The type of urgent genetic test differed among centers, with gene panels being the most frequently available (N = 31, 32.3%), followed by all types of genetic testing except WGS (12.9%). The respondents' comments indicated the possibility of an urgent test only in specific situations such as prenatal confirmation of a genetic disease, treatable conditions, critically ill patients, or in some cases of developmental and epileptic encephalopathies. Two respondents commented that genetic counseling or discussion of the treating physician with the geneticist regarding urgent testing is usually needed before prescription. The median time‐to‐result of the urgent genetic was 3 weeks (N = 17, variance: 2 days to 8 weeks).

3.2.5. Time‐to‐result

The average time needed for results to be returned to the clinician had a significant variance per test and country, ranging from a few weeks to more than a year. As expected, the results of WES and WGS are the most time‐consuming, with a median time‐to‐result across centers that was estimated at six (variance: 1.5 to 32 months) and six and a half months, respectively (variance: 1.5 to 19 months). The median time‐to‐result (in weeks) and the variance per test across centers, as reported by the clinicians, are explicitly presented in Table 2.

3.3. Common practices regarding genetic testing

The clinicians were asked to indicate whether and which test(s) and in which order they would prescribe in specific clinical situations based on the phenotype.

The tests selected most frequently were as follows: WES (36.8%) for neurodevelopmental encephalopathy with epilepsy as a secondary feature; epilepsy gene panel for neonatal/infantile developmental and epileptic encephalopathy (DEE) (36%), non‐lesional focal epilepsy (38%), electroclinical phenotype suggestive of a specific diagnosis (43%), epilepsy related to structural/cortical malformations (34.9%), and epilepsy syndromes with an established genetic heterogeneity (47.8%); no genetic testing (35.5%) for idiopathic generalized epilepsies. Figure 2 illustrates the distribution of choices for two of the above scenarios, and more specifically in the case of an epilepsy related to structural/cortical malformations and in the case of a neurodevelopmental encephalopathy with epilepsy as a secondary feature.

FIGURE 2.

Distribution of answers regarding the genetic test choice in case of (A) epilepsy related to structural/cortical malformations and (B) neurodevelopmental encephalopathy with epilepsy as a secondary feature. N ^A = times that this specific test appeared among the clinician's choices for scenario A (N = 43 answers); N ^B = times that this specific test appeared among the clinician's choices for scenario B (N = 44 answers); MS‐MLPA, methylation‐sensitive multiplex ligation‐dependent probe analysis.

There was no correlation between the country of practice and the first genetic test the practitioner chooses in the above scenarios.

4. DISCUSSION

The ongoing revolution in epilepsy genetics offers the possibility of early diagnosis and application of precision medicine and personalized treatments that may have a critical impact on the evolution of patients suffering from rare epilepsies. ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ In this era, optimizing the accessibility and availability of genetic testing to all patients suffering from epilepsies is essential. This survey has brought to light several discrepancies in the provision of genetic testing for epilepsy across Europe.

Although most of the routinely used genetic tests are widely accessible, WGS is unavailable in almost half of the reference centers. Yet, a recent systematic review and meta‐analysis comparing the diagnostic yield of most commonly used genetic tests in patients with epilepsy supports that the diagnostic yield of genome sequencing is as high as 48%, followed by exome sequencing (24%), gene panels (19%), and array‐CGH/chromosomal micro‐array (9%). ¹⁶ Although the authors recognize as a limitation the high heterogeneity of the studies included in the meta‐analysis, especially regarding the reporting of the epilepsy, subsequent international cohort studies further support the accuracy of the estimated WGS diagnostic yield. ¹⁷

In detail, D′ Gamma at al recently reported results from the application of rapid genome sequencing (median time to genetic result from seizure onset: 37 days) in the context of an international, multicenter, pilot, cohort study in 100 infants with new‐onset epilepsy. The diagnostic yield was calculated at 43%, while immediate therapeutic utility of the positive result was recognized in more than half of the cases (56%), further underlying the interest of accessibility to urgent genetic testing. ¹⁷ Although promising in a research setting of highly specialized centers of four high resource countries (Australia, Canada, UK, and USA), the feasibility, cost‐effectiveness, and implementation in clinical practice of such a model at a European level seem very distant, given the pronounced differences across countries.

In fact, regarding costs and time to deliver the results to the clinician for different genetic tests across ERN EpiCARE centers, the availability is highly heterogeneous according to our survey (Table 2), even in the setting of a clinical situation estimated as urgent. Nevertheless, the high diagnostic and therapeutic yield (>50%) of genetic testing, especially for specific indications (i.e., neonatal/early infantile onset focal epilepsy or DEE) ¹⁷ , ²⁰ urges the need for timely genetic results, especially in the context of critically ill patients. Urgent genetic testing is still unavailable in around 1/3 of the interviewed EpiCARE centers. Another interesting finding is that some EpiCARE centers (i.e., in France) have reported no access to urgent testing, although there are newly established national protocols for access to genetic testing in collaboration with specific national epilepsy reference centers. This rather surprising finding suggests that the scientific societies and the (inter)national health authorities have to further invest in educating/informing the clinicians on the genetic testing possibilities in a regional, national, and international scale.

Genetic testing was not part of the factors measured in the previous European epilepsy care provision study ESBACE. ¹⁵ However, genetic testing has emerged as an indispensable tool in epilepsy care. ⁴ , ⁵ , ⁶ We have thus attempted to use some common representation methods in order to provide an insight on the topic, as illustrated in the maps created for the needs of this project. In fact, according to our survey, the Western countries seem to be better provided in terms of genetic testing, as they were better provided for the indication factors of epilepsy care measured for the ESBACE study. Another consistent result between the two surveys is the underrepresentation of Central and Eastern European countries, reflecting that there are less EpiCARE centers in these areas. ERNs facilitate data/information sharing. The organization of epilepsy care, the access to specialized epilepsy centers, and the availability of genetic testing in these areas need further investigation.

Access to specialized epilepsy centers fulfilling specific criteria is essential for optimal diagnostic and therapeutic management, especially for patients with drug‐resistant or rare epilepsies. ²¹ The US National Association of Epilepsy Centers has recently published consensus‐based recommendations on specialized epilepsy centers. They included recommendations on utilization of genetic testing as part of the diagnostic work‐up based on specific protocols and access to a certified genetic counselor either within the center or by referral. ²² Efforts to collect and compare data and adopt/develop specific recommendations for European centers should continue, also considering differences in healthcare systems.

The differences regarding epilepsy genetic testing across Europe may be related to a variety of factors, including government policies, healthcare systems, and differences in economic resources. Each European country has its own policies and regulatory frameworks regarding genetic testing, which can impact the availability and accessibility of testing. Some countries may have more restrictive policies, while others may be more permissive. In some countries, genetic testing may be fully covered by national healthcare programs, while in others, patients may have to pay for testing out of pocket. In our survey, in almost 2/3 of cases, genetic testing was fully reimbursed; however, there were remarkable differences in pricing even within the same country. We have not asked the practitioners whether the prices provided for the genetic testing refer to private/public settings. However, the differences, that may raise up to nine times the price for the same genetic test in one center compared to another, raise reasonable concerns regarding equal access to genetic testing of all European patients.

Economic resources also play a role in the availability and accessibility of genetic testing. Countries with higher levels of economic development may have more resources to invest in genetic testing, while countries with fewer resources may have more limited access to testing. Notably, access to genetic testing in low‐income countries, especially to the most modern techniques, can be limited due to various factors, such as lack of infrastructure, funding, trained personnel, and awareness about the benefits of genetic testing. Nevertheless, a positive finding of our survey was that all but one centers had access to at least one NGS technique. NGS is indicated in the vast majority of epilepsy syndromes according to the update on clinical genetic testing of the Genetics Commission of the International League Against Epilepsy (ILAE). ²⁰

Regarding choice and prioritization of available genetic tests in common clinical scenarios of everyday practice, there is a considerable variance even among experts, with a maximum of 47.8% agreement rate per test and scenario, irrespective of the country of practice. This finding probably implies the presence of genetic prescription preferences that may interfere with care standardization processes. ²³ However, the most frequently chosen answers of the experts are quite in line with what is proposed by the Genetics Commission of the ILAE. ²⁰ Most clinicians indicate gene panel, followed by WES, as the first‐intention genetic test to be prescribed for the specific clinical scenarios included in the survey. According to the ILAE's paper, WES/WGS, when available, should be prescribed at first intention for these scenarios, but the authors propose that an epilepsy panel including all relevant genes could be considered alternatively. ²⁰

Regardless of the perspective approach of the differences mentioned above, a critical concept that emerges from our study is the need to harmonize genetic testing protocols; this need has previously also been underscored for the harmonization of clinical practice in specific rare and complex epilepsies. ²⁴ Fortunately, the situation across Europe is changing, with many countries adopting new policies, regulations, and technologies to provide better access to genetic testing. There are also several initiatives that can be pursued to foster knowledge on this topic.

The ERN EpiCARE represents a major actor in this process and is already supporting many relevant activities: (i) Patient education programs—developing educational programs that provide patients with accurate and comprehensive information about genetic testing options, the benefits and risks, and how to make informed decisions; (ii) Provider education—Providing healthcare providers with continuing education opportunities to stay up‐to‐date on the latest genetic testing options, guidelines, and best practices so that they can provide accurate and informed recommendations to their patients; (iii) Genetic counseling—Offering, between others, genetic counseling services to medical teams, using a secured case patient management system, funded by the European Commission. A resource helps patients and clinicians to better understand genetic testing implications and to make informed, and possibly cost‐effective, decisions; (iv) Research and evaluation—Fostering research and evaluation of genetic testing options to ensure that the most accurate and reliable tests are available to patients and healthcare providers irrespective of the European Region. For example, EpiCARE is working on developing an algorithm to support education and training for the new classification of epilepsy syndromes with focus on genetic etiologies.

European Patient Advocacy Groups (ePAGs) will also be critical in pursuing equality in genetic testing and other healthcare policies. For example, ePAGS for specific genetic conditions can provide support and resources to raise awareness and advocate for better diagnostic options. These aspects are particularly relevant as genetic testing of individuals with epilepsy may be materially associated with clinical decision‐making and improved patient outcomes. ²⁵ The genetic diagnosis might be relevant for the choice of appropriate antiseizure medications, avoiding drugs which might even worsen seizures, and giving the opportunity to participate in clinical trials for epilepsy due to specific genetic etiologies.

Limitations of the current survey include the following: (i) the recruitment was limited to ERN EpiCARE centers, which do not equally represent all European areas (overrepresentation of Western European countries) and genetic practices, considering that other non‐EpiCARE‐labeled national epilepsy centers, other Health Care Providers, and/or smaller hospitals also care for patients with rare or complex forms of epilepsy with a possible genetic etiology; (ii) the questionnaire did not include items related to the existence of already used genetic testing protocols, to access to genetic counseling before/after genetic testing or to differences between public/private options available in each country; (iii) the questionnaire was mainly based on close‐ended questions, which, while useful for quickly gathering quantitative data, can be limited in providing detailed and nuanced information.

5. CONCLUSIONS

Access to WGS and to urgent genetic testing is not yet widely available across ERN EpiCARE centers, while costs, time to deliver the results to the clinician, and choice of first‐intention genetic testing are highly variable. The harmonization of the availability and administration of genetic tests in Europe and the guidance for optimal test choices remain essential to avoid diagnostic delays and to optimize costs and management of persons with epilepsy of genetic etiology. National healthcare authorities need to collaborate regularly with the ERNs and their respective scientific societies in implementing guidelines and recommendations based on expertise in rare and complex epilepsies.

AUTHOR CONTRIBUTIONS

M.T.P. and A.A. conceived the idea of the survey and the Ddares project. N.S., M.T., A.K., and G.L. have created the questionnaire that was then reviewed by all authors before distribution. M.T.P, T.K., and C.F. have analyzed the data. M.T.P. and L.M. wrote the draft manuscript with support from F.B, A.K., and G.L. All authors discussed the results and contributed to the final manuscript.

FUNDING INFORMATION

This survey was conducted as part of the ERN EpiCARE Ddares project funded by the European Union and the Connecting Europe Facility (CEF Telecom) 2020 grant. Management of the ERN EpiCARE, coordinated by the Hospices Civils de Lyon, is funded by the European Commission.

CONFLICT OF INTEREST STATEMENT

None of the authors has any conflict of interest to disclose. All authors confirm to have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Supporting information

Appendix S1:

Appendix S2:

Appendix S3:

Papadopoulou MT, Muccioli L, Bisulli F, Klotz KA, Fons C, Trivisano M, et al. Accessibility, availability and common practices regarding genetic testing for epilepsy across Europe: A survey of the European Reference Network EpiCARE . Epilepsia Open. 2024;9:996–1006. 10.1002/epi4.12930