{"id":"0c9acf07cf07","type":"article","url":"https://hartvaat.nl/2026/05/14/eas-fhsc-wereldwijd-onderzoek-toont-grote-variatie-in-genetische-fh-diagnostiek-/","title":"EAS FHSC: wereldwijd onderzoek toont grote variatie in genetische FH-diagnostiek — pleidooi voor standaardisatie","title_en":"Global survey of genetic testing methods for familial hypercholesterolemia. A study and recommendations from the EAS FHSC registry.","category":"cholesterol","category_label":"Cholesterol","professions":["cardioloog","huisarts","internist"],"tags":["familiaire-hypercholesterolemie","familiaire-hypercholesterolemie-screening"],"journal":"European journal of preventive cardiology","doi":"10.1093/eurjpc/zwag198","source_url":"https://doi.org/10.1093/eurjpc/zwag198","authors":["Joana Rita Chora","Irene Karungi","Amany Elshorbagy","Christophe A T Stevens","Antonio J Vallejo-Vaz","Kanika I Dharmayat","Marianne Abifadel","Carlos A Aguilar-Salinas","Khalid F Alhabib","Wael Almahmeed","Fahad Alnouri","Rodrigo Alonso","Khalid Al-Rasadi","Ahmad Al-Sarraf","Marcello Arca","Engy A Ashaat","Tester F Ashavaid","Maurizio Averna","Maciej Banach","Marianne Becker","Christoph J Binder","Liam R Brunham","Alberico L Catapano","Pablo Corral","Olivier S Descamps","Euridiki Drogari","Ronen Durst","Marat Ezhov","Urh Groselj","Mariko Harada-Shiba","Kirsten B Holven","G Kees Hovingh","Weerapan Khovidhunkit","Katarina Lalic","Gustavs Latkovskis","Ulrich Laufs","Evangelos Liberopoulos","Jie Lin","Winfried März","Pedro Mata","Anne Thushara Matthias","André R Miserez","Olena Mitchenko","Hapizah Mohd Nawawi","Børge G Nordestgaard","Andrie G Panayiotou","György Paragh","Zaneta Petrulioniene","Arman Postadzhiyan","Ximena Reyes","Fouzia Sadiq","Amirhossein Sahebkar","Raul D Santos","J P S Sawhney","Heribert Schunkert","Swarup A V Shah","Aleksandr B Shek","Handrean Soran","Ta-Chen Su","Tavintharan Subramaniam","Myra Tilney","Brian Tomlinson","Thanh Huong Truong","Anne Tybjærg-Hansen","Margus Viigimaa","Branislav Vohnout","Gerald F Watts","Shizuya Yamashita","Kausik K Ray","Frederick J Raal","Steve E Humphries","Tomas Freiberger","Mafalda Bourbon"],"significance":7,"published":"2026-06-04","source_date":"2026-05-14","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/genetisch-onderzoek-fh/","https://hartvaat.nl/kennis/lipiden/familiaire-hypercholesterolemie/"],"congress":"","summary_en":"International survey among national lead-investigators of the European Atherosclerosis Society FH-Studies Collaboration from 55 of 68 countries (81% response; Africa 2, Americas 6, Asia 20, Europe 26, Oceania 1). Referral criteria were most often the Dutch Lipid Clinic Network score (adults 72%, children 57%); Simon Broome and MEDPED were used only in high-income countries. For index patients, next-generation sequencing predominated (62%); for relatives, Sanger sequencing (71%). Copy-number variants were assessed by 65% of centres, mostly via NGS platforms. Nearly all centres screened LDLR (100%), APOB (97%), and PCSK9 (95%); pathogenicity was interpreted largely per ACMG guidelines. The authors call for global standardisation: at minimum the three FH genes, ideally also the five associated/phenocopy genes.","created":"2026-07-03T10:32:29Z","updated":"2026-07-03T13:31:26Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Internationale enquête onder national lead-investigators van de European Atherosclerosis Society FH-Studies Collaboration uit 55 van 68 landen (81% respons; Afrika 2, Amerika 6, Azië 20, Europa 26, Oceanië 1). Verwijscriterium was meestal de Dutch Lipid Clinic Network-score (volwassenen 72%, kinderen 57%); Simon Broome en MEDPED werden alleen in hoge-inkomenslanden toegepast. Voor indexpatiënten werd vooral next-generation sequencing (62%) gebruikt; voor familieleden Sanger-sequencing (71%). Copy-number-varianten werden door 65% van de centra meegenomen, vooral via NGS-platforms. Vrijwel alle centra screenden LDLR (100%), APOB (97%) en PCSK9 (95%); pathogeniciteit werd grotendeels volgens ACMG-richtlijnen geïnterpreteerd. De auteurs roepen op tot mondiale standaardisatie: minimaal de drie FH-genen, idealiter ook de vijf geassocieerde/phenocopy-genen.","abstract_original":"BACKGROUND AND AIMS: Familial hypercholesterolemia (FH), primarily caused by pathogenic LDLR, APOB, or PCSK9 variants, results in elevated LDL-C and increased cardiovascular risk. Genetic testing offers the definitive diagnosis, yet global approaches to FH genetic testing remain unstandardized. We investigate current testing practices worldwide and provide relevant recommendations. METHODS: A survey was distributed to national lead-investigators (NLIs) of 68 countries in the FH-Studies Collaboration, assessing referral criteria, assay methodologies, target genes, and pathogenicity interpretation methods. RESULTS: NLIs from centres in 55/68 countries (81%) responded, spanning Africa (N=2), Americas (N=6), Asia (N=20), Europe (N=26), and Oceania (N=1). DLCN scores were the most common reason for referral to genetic testing (adults:72%; children:57%). Simon Broome and MEDPED criteria were reported only by centres from high-income countries (adults: 7% and 2%; children: 12% and 2%). Methods for testing in index versus non-index cases were significantly different (p <0.001). Next-generation sequencing (NGS) was the predominant assay method for index cases (62%), while Sanger sequencing was favoured for non-index (71%). However, these testing techniques did not differ between centres from high- and non-high-income countries for index cases (p=0.74) and non-index cases (p=0.49). Copy-number variants (CNVs) were assessed by 65% of centres, with most integrating CNV analysis into NGS platforms (86%) and others (14%) using multiplex ligation-dependent probe-amplification (MLPA) or microarrays. Screening encompassed LDLR (100%), APOB (97%), PCSK9 (95%), and other genes. Most centres (96%) incorporated pathogenicity interpretation into their reports, adhering largely to American College of Medical Genetics and Genomics guidelines. CONCLUSIONS: FH genetic testing practices vary widely across countries surveyed, emphasizing the need for global standardization to enhance accuracy and comparability of FH diagnoses worldwide. We suggest that genetic testing should include the three FH-causing genes and ideally the five associated/phenocopy genes."}