Multicenter clinical trials

Effectiveness of Somatostatin Analogues in Patients with hereditary hemorrhagic telangiectasia and symptomatic gastrointestinal bleeding, the SAIPAN-trial: a multicenter, randomized, open-label, parallelgroup, superiority trial: Danish, French, Italian and Netherlands HCPs participating

• Year 1 Collaborative Publications

Executive summary of the 12th HHT international scientific conference.Andrejecsk JW, Hosman AE, Botella LM, Shovlin CL, Arthur HM, Dupuis-Girod S, Buscarini E, Hughes CCW, Lebrin F, Mummery CL, Post MC, Mager JJ. Angiogenesis.2017 Nov 16.doi: 10.1007/s10456-017-9585-2. [Epub ahead of print] PMID: 29147802

Long-term outcomes of patients with pulmonary arteriovenous malformations considered for lung transplantation, compared with similarly hypoxaemic cohorts. Shovlin CL, Buscarini E, Hughes JMB, Allison DJ, Jackson JE. BMJ Open Respir Res. 2017 Oct 13;4(1):e000198. doi: 10.1136/bmjresp-2017-000198. eCollection 2017.PMID: 29071074

*The Lung in Hereditary Hemorrhagic Telangiectasia. Dupuis-Girod S, Cottin V, Shovlin CL. Respiration. 2017;94(4):315-330. doi: 10.1159/000479632. Epub 2017 Aug 30. PMID: 28850955

Response to Bevacizumab for the treatment of Rendu-Osler disease-A note of caution.Dupuis-Girod S, Buscarini E.Liver Int. 2017 Jun;37(6):928. doi: 10.1111/liv.13385. No abstract available. PMID: 28544692

• Year 2 Collaborative Publications

*Safety of thalidomide and bevacizumab in patients with hereditary hemorrhagic telangiectasia. Buscarini E, Botella LM, Geisthoff U, Kjeldsen AD, Mager HJ, Pagella F, Suppressa P, Zarrabeitia R, Dupuis-Girod S, Shovlin CL; VASCERN-HHT. Orphanet J Rare Dis. 2019 Feb 4;14(1):28. doi: 10.1186/s13023-018-0982-4. PMID: 30717761 Orphanet J Rare Dis. 2018 Aug 15;13(1):136. doi: 10.1186/s13023-018-0850-2.

*European Reference Network For Rare Vascular Diseases (VASCERN) Outcome Measures For Hereditary Haemorrhagic Telangiectasia (HHT). Shovlin CL1,2, Buscarini E3, Kjeldsen AD4, Mager HJ5, Sabba C6, Droege F7, Geisthoff U7,8, Ugolini S9, Dupuis-Girod S10,11. Haematologica. 2019 Feb;104(2):e85-e86. doi: 10.3324/haematol.2018.209791.

*Prevention of serious infections in hereditary hemorrhagic telangiectasia: roles for prophylactic antibiotics, the pulmonary capillaries-but not vaccination. Shovlin C1, Bamford K2, Sabbà C3, Mager HJ4, Kjeldsen A5, Droege F6, Buscarini E7, Dupuis-Girod S8; VASCERN HHT. Haematologica. 2019 Feb;104(2):e85-e86. doi: 10.3324/haematol.2018.209791. No abstract available.

• Year 3-5 Collaborative Publications

*Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia. Shovlin CL, Millar CM, Droege F, Kjeldsen A, Manfredi G, Suppressa P, Ugolini S, Coote N, Fialla AD, Geisthoff U, Lenato GM, Mager HJ, Pagella F, Post MC, Sabbà C, Sure U, Torring PM, Dupuis-Girod S, Buscarini E; VASCERN-HHT. Orphanet J Rare Dis. 2019 Aug 28;14(1):210. doi: 10.1186/s13023-019-1179-1.

*European Reference Network for Rare Vascular Diseases (VASCERN) position statement on cerebral screening in adults and children with hereditary haemorrhagic telangiectasia (HHT). Eker OF, Boccardi E, Sure U, Patel MC, Alicante S, Alsafi A, Coote N, Droege F, Dupuis O, Fialla AD, Jones B, Kariholu U, Kjeldsen AD, Lefroy D, Lenato GM, Mager HJ, Manfredi G, Nielsen TH, Pagella F, Post MC, Rennie C, Sabbà C, Suppressa P, Toerring PM, Ugolini S, Buscarini E, Dupuis-Girod S, Shovlin CL. Orphanet J Rare Dis. 2020 Jun 29;15(1):165. doi: 10.1186/s13023-020-01386-9. PMID: 32600364

Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Faughnan ME, Mager JJ, Hetts SW, Palda VA, Lang-Robertson K, Buscarini E, Deslandres E, Kasthuri RS, Lausman A, Poetker D, Ratjen F, Chesnutt MS, Clancy M, Whitehead KJ, Al-Samkari H, Chakinala M, Conrad M, Cortes D, Crocione C, Darling J, de Gussem E, Derksen C, Dupuis-Girod S, Foy P, Geisthoff U, Gossage JR, Hammill A, Heimdal K, Henderson K, Iyer VN, Kjeldsen AD, Komiyama M, Korenblatt K, McDonald J, McMahon J, McWilliams J, Meek ME, Mei, Zahav M, Olitsky S, Palmer S, Pantalone R, Piccirillo JF, Plahn B, Porteous MEM, Post MC, Radovanovic I, Rochon PJ, Rodriguez-Lopez J,– Sabba C, Serra M, Shovlin C, Sprecher D, White AJ, Winship I, Zarrabeitia R. Ann Intern Med. 2020 Dec 15;173(12):989-1001. doi: 10.7326/M20-1443. Epub 2020 Sep 8. PMID: 32894695.

*The European rare disease network for HHT frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care. Shovlin CL, Buscarini E, Sabbà C, Mager HJ, Kjeldsen AD, Pagella F, Sure U, Ugolini S, Toerring PM, Suppressa P, Rennie C, Post MC, Patel MC, Nielsen TH, Manfredi G, Lenato GM, Lefroy D, Kariholu U, Jones B, Fialla AD, Eker OF, Dupuis O, Droege F, Coote N, Boccardi E, Alsafi A, Alicante S, Dupuis-Girod S. Eur J Med Genet. 2021 Nov 1:104370. doi: 10.1016/j.ejmg.2021.104370. Online ahead of print.
PMID: 34737116

*European Reference Network for Rare Vascular Diseases (VASCERN): When and how to use intravenous bevacizumab in Hereditary Haemorrhagic Telangiectasia (HHT)? Dupuis-Girod S, Shovlin CL, Kjeldsen AD, Mager HJ, Sabba C, Droege F, Fargeton AE, Fialla AD, Gandolfi S, Hermann R, Lenato GM, Manfredi G, Post MC, Rennie C, Suppressa P, Sure U; ePag group, Buscarini E. Eur J Med Genet. 2022 Aug 5;65(10):104575. doi: 10.1016/j.ejmg.2022.104575. Epub ahead of print. PMID: 35940549.

*=VASCERN acknowledged

Current collaborative research studies ongoing 

• F101 Genomes study: Paris, Ghent and Antwerp HCPs involved
• Arrhythmias and cardiac function in heritable thoracic aortic diseases: Barcelona, Malta, Paris, Ghent, and Hamburg HCPs involved

Year 1: Collaborative Publications

Arterial tortuosity syndrome: 40 new families and literature review.Beyens A, Albuisson J, Boel A, Al-Essa M, Al-Manea W, Bonnet D, Bostan O, Boute O, Busa T, Canham N, Cil E, Coucke PJ, Cousin MA, Dasouki M, De Backer J, De Paepe A, De Schepper S, De Silva D, Devriendt K, De Wandele I, Deyle DR, Dietz H, Dupuis-Girod S, Fontenot E, Fischer-Zirnsak B, Gezdirici A, Ghoumid J, Giuliano F, Diéz NB, Haider MZ, Hardin JS, Jeunemaitre X, Klee EW, Kornak U, Landecho MF, Legrand A, Loeys B, Lyonnet S, Michael H, Moceri P, Mohammed S, Muiño-Mosquera L, Nampoothiri S, Pichler K, Prescott K, Rajeb A, Ramos-Arroyo M, Rossi M, Salih M, Seidahmed MZ, Schaefer E, Steichen-Gersdorf E, Temel S, Uysal F, Vanhomwegen M, Van Laer L, Van Maldergem L, Warner D, Willaert A, Collins TR, Taylor A, Davis EC, Zarate Y, CallewaertB.Genet Med. 2018 Jan 11. doi: 10.1038/gim.2017.253. [Epub ahead of print] PMID: 29323665

Pregnancy in Women With SMAD3 Mutation.van Hagen IM, van der Linde D, van de Laar IM, MuiñoMosquera L, De Backer J, Roos-Hesselink JW. J Am CollCardiol. 2017 Mar 14;69(10):1356-1358. doi: 10.1016/j.jacc.2016.12.029. No abstract available. PMID: 28279300

Organisation of care for pregnancy in patients with congenital heart disease. Roos-Hesselink JW1, Budts W2, Walker F3, De Backer JFA4, Swan L5, Stones W6,7, Kranke P8,9, Sliwa-Hahnle K10,11, Johnson MR12. Heart. 2017 Dec;103(23):1854-1859. doi: 10.1136/heartjnl-2017-311758. Epub 2017 Jul 24. PMID: 28739807

Homozygous and compound heterozygous mutations in the FBN1 gene: unexpected findings in molecular diagnosis of Marfan syndrome.Arnaud P, Hanna N, Aubart M, Leheup B, Dupuis-Girod S, Naudion S, Lacombe D, Milleron O, Odent S, Faivre L, Bal L, Edouard T, Collod-Beroud G, Langeois M, Spentchian M, Gouya L, Jondeau G, Boileau C.J Med Genet. 2017 Feb;54(2):100-103. doi: 10.1136/jmedgenet-2016-103996. Epub 2016 Aug 31. PMID: 27582083

Impaired Central Pulsatile Hemodynamics in Children and Adolescents With Marfan Syndrome. Grillo A, Salvi P, Marelli S, Gao L, Salvi L, Faini A, Trifirò G, Carretta R, Pini A, Parati G. J Am Heart Assoc. 2017 Nov 7;6(11):e006815. doi: 10.1161/JAHA.117.006815. PMID: 29114001; PMCID: PMC5721771.

A mutation update on the LDS associated genes TGFB2/3 and SMAD2/3. Schepers D, Tortora G, Morisaki H, MacCarrick G, Lindsay M, Liang D, Mehta SG, Hague J, Verhagen J, van de Laar I, Wessels M, Detisch Y, van Haelst M, Baas A, Lichtenbelt K, Braun K, van der Linde D, Roos-Hesselink J, McGillivray G, Meester J, Maystadt I, Coucke P, El-Khoury E, Parkash S, Diness B, Risom L, Scurr I, Hilhorst-Hofstee Y, Morisaki T, Richer J, Désir J, Kempers M, Rideout AL, Horne G, Bennett C, Rahikkala E, Vandeweyer G, Alaerts M, Verstraeten A, Dietz H, Van Laer L, Loeys B. Hum Mutat. 2018 Feb 1. doi: 10.1002/humu.23407. [Epub ahead of print]

Year 2 : Collaboarative  Publications

SMAD3 pathogenic variants: risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium. Hostetler EM, Regalado ES, Guo DC, Hanna N, Arnaud P, Muiño-Mosquera L, Callewaert BL, Lee K, Leal SM, Wallace SE, Rideout AL, Dyack S, Aatre RD, Boileau C, De Backer J, Jondeau G, Milewicz DM.J Med Genet. 2019 Jan 19. pii: jmedgenet-2018-105583. doi: 10.1136/jmedgenet-2018-105583. [Epub ahead of print] PMID: 30661052

Hungarian Marfan family with large FBN1 deletion calls attention to copy number variation detection in the current NGS era. Benke K, Ágg B, Meienberg J, Kopps AM, Fattorini N, Stengl R, Daradics N, Pólos M, Bors A, Radovits T, Merkely B, De Backer J, Szabolcs Z, Mátyás G.J Thorac Dis. 2018 Apr;10(4):2456-2460. doi: 10.21037/jtd.2018.04.40. PMID: 29850152

Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection.Renard M, Francis C, Ghosh R, Scott AF, Witmer PD, Adès LC, Andelfinger GU, Arnaud P, Boileau C, Callewaert BL, Guo D, Hanna N, Lindsay ME, Morisaki H, Morisaki T, Pachter N, Robert L, Van Laer L, Dietz HC, Loeys BL, Milewicz DM, De Backer J. J Am Coll Cardiol. 2018 Aug 7;72(6):605-615. doi: 10.1016/j.jacc.2018.04.089.PMID: 30071989

Expert consensus recommendations on the cardiogenetic care for patients with thoracic aortic disease and their first-degree relatives.Verhagen JMA, Kempers M, Cozijnsen L, Bouma BJ, Duijnhouwer AL, Post JG, Hilhorst-Hofstee Y, Bekkers SCAM, Kerstjens-Frederikse WS, van Brakel TJ, Lambermon E, Wessels MW, Loeys BL, Roos-Hesselink JW, van de Laar IMBH; National Working Group on BAV & TAA. Int J Cardiol. 2018 May 1;258:243-248. doi: 10.1016/j.ijcard.2018.01.145. Epub 2018 Feb 7. Review. PMID: 29452988

Results of next-generation sequencing gene panel diagnostics including copy-number variation analysis in 810 patients suspected of heritable thoracic aortic disorders. Overwater E, Marsili L, Baars MJH, Baas AF, van de Beek I, Dulfer E, van Hagen JM, Hilhorst-Hofstee Y, Kempers M, Krapels IP, Menke LA, Verhagen JMA, Yeung KK, Zwijnenburg PJG, Groenink M, van Rijn P, Weiss MM, Voorhoeve E, van Tintelen JP, Houweling AC, Maugeri A.Hum Mutat. 2018 Sep;39(9):1173-1192. doi: 10.1002/humu.23565. Epub 2018 Jul 12.

Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype.Cannaerts E, Kempers M, Maugeri A, Marcelis C, Gardeitchik T, Richer J, Micha D, Beauchesne L, Timmermans J, Vermeersch P, Meyten N, Chénier S, van de Beek G, Peeters N, Alaerts M, Schepers D, Van Laer L, Verstraeten A, Loeys B.J Med Genet. 2018 Jul 2. pii: jmedgenet-2018-105304. doi: 10.1136/jmedgenet-2018-105304. [Epub ahead of print]PMID: 29967133

A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3.Schepers D, Tortora G, Morisaki H, MacCarrick G, Lindsay M, Liang D, Mehta SG, Hague J, Verhagen J, van de Laar I, Wessels M, Detisch Y, van Haelst M, Baas A, Lichtenbelt K, Braun K, van der Linde D, Roos-Hesselink J, McGillivray G, Meester J, Maystadt I, Coucke P, El-Khoury E, Parkash S, Diness B, Risom L, Scurr I, Hilhorst-Hofstee Y, Morisaki T, Richer J, Désir J, Kempers M, Rideout AL, Horne G, Bennett C, Rahikkala E, Vandeweyer G, Alaerts M, Verstraeten A, Dietz H, Van Laer L, Loeys B. Hum Mutat. 2018 May;39(5):621-634. doi: 10.1002/humu.23407. Epub 2018 Mar 6. PMID: 29392890

Year 3-5 Collaborative Publications

athogenic variants in THSD4, encoding the ADAMTS-like 6 protein, predispose to inherited thoracic aortic aneurysm. Elbitar S, Renard M, Arnaud P, Hanna N, Jacob MP, Guo DC, Tsutsui K, Gross MS, Kessler K, Tosolini L, Dattilo V, Dupont S, Jonquet J, Langeois M, Benarroch L, Aubart M, Ghaleb Y, Abou Khalil Y, Varret M, El Khoury P, Ho-Tin-Noé B, Alembik Y, Gaertner S, Isidor B, Gouya L, Milleron O, Sekiguchi K, Milewicz D, De Backer J, Le Goff C, Michel JB, Jondeau G, Sakai LY, Boileau C, Abifadel M.Genet Med. 2020 Aug 28. doi: 10.1038/s41436-020-00947-4. Online ahead of print.PMID: 32855533

*Features of Marfan syndrome not listed in the Ghent nosology – The Dark Side of the Disease.von Kodolitsch Y, Demolder A, Girdauskas E, Kaemmerer H, Kornhuber K, Muino Mosquera L, Morris S, Neptune E, Pyeritz R, Rand-Hendriksen S, Rahman A, Riise N, Robert L, Staufenbiel I, Szöcs K, Vanem TT, Linke SJ, Vogler M, Yetman A, De Backer J.Expert Rev Cardiovasc Ther. 2019 Dec 12. doi: 10.1080/14779072.2019.1704625. [Epub ahead of print]PMID: 31829751

*J Clin Med. 2019 Nov 29;8(12). pii: E2079. doi: 10.3390/jcm8122079. Case-matched Comparison of Cardiovascular Outcome in Loeys-Dietz Syndrome versus Marfan Syndrome. Mühlstädt K1, De Backer J2,3, von Kodolitsch Y1, Kutsche K4, Muiño Mosquera L2, Brickwedel J1, Girdauskas E1, Mir TS1, Mahlmann A5, Tsilimparis N1, Staebler A6, Schoof L1, Seidel H7, Berger J8, Bernhardt AM1, Blankenberg S1, Kölbel T1, Detter C1, Szöcs K1, Kaemmerer H9.

*European reference network for rare vascular diseases (VASCERN) consensus statement for the screening and management of patients with pathogenic ACTA2 variants. van de Laar IMBH, Arbustini E, Loeys B, Björck E, Murphy L, Groenink M, Kempers M, Timmermans J, Roos-Hesselink J, Benke K, Pepe G, Mulder B, Szabolcs Z, Teixidó-Turà G, Robert L, Emmanuel Y, Evangelista A, Pini A, von Kodolitsch Y, Jondeau G, De Backer J.Orphanet J Rare Dis. 2019 Nov 21;14(1):264. doi: 10.1186/s13023-019-1186-2.PMID: 31752940 Free PMC Article

*Genetic counselling and testing in adults with congenital heart disease: A consensus document of the ESC Working Group of Grown-Up Congenital Heart Disease, the ESC Working Group on Aorta and Peripheral Vascular Disease and the European Society of Human Genetics.De Backer J, Bondue A, Budts W, Evangelista A, Gallego P, Jondeau G, Loeys B, Peña ML, Teixido-Tura G, van de Laar I, Verstraeten A, Roos Hesselink J.Eur J Prev Cardiol. 2019 Jun 11:2047487319854552. doi: 10.1177/2047487319854552. [Epub ahead of print]PMID: 31184212

*Curr Opin Cardiol. 2019 Aug 7. doi: 10.1097/HCO.0000000000000669. [Epub ahead of print]Genetic testing for aortopathies: primer for the nongeneticist. De Backer J1,2, Jondeau G3,2, Boileau C3,4,5.

Eur Heart J. 2019 Mar 25. pii: ehz136. doi: 10.1093/eurheartj/ehz136. [Epub ahead of print] Pregnancy outcomes in women with cardiovascular disease: evolving trends over 10 years in the ESC Registry Of Pregnancy And Cardiac disease (ROPAC).Roos-Hesselink J1,2, Baris L1, Johnson M3, De Backer J4, Otto C5, Marelli A6, Jondeau G7, Budts W8, Grewal J9, Sliwa K10, Parsonage W11, Maggioni AP2,12, van Hagen I1, Vahanian A2,7, Tavazzi L13, Elkayam U14, Boersma E1, Hall R15.

Myocardial Function, Heart Failure and Arrhythmia in Marfan Syndrome: A Systematic Literature Review. Demolder A, von Kodolitsch Y, Muiño-Mosquera L, De Backer J. Diagnostics (Basel). 2020 Sep 25;10(10):751. doi: 10.3390/diagnostics10100751. PMID: 32992882; PMCID: PMC7599866.

*Pregnancy outcome in thoracic aortic disease data from the Registry Of Pregnancy And Cardiac disease. Campens L, Baris L, Scott NS, Broberg CS, Bondue A, Jondeau G, Grewal J, Johnson MR, Hall R, De Backer J, Roos-Hesselink JW; ROPAC investigators group.Heart. 2021 Jan 19:heartjnl-2020-318183. doi: 10.1136/heartjnl-2020-318183. Online ahead of print.PMID: 33468574

Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO.de la Fuente-Alonso A, Toral M, Alfayate A, Ruiz-Rodríguez MJ, Bonzón-Kulichenko E, Teixido-Tura G, Martínez-Martínez S, Méndez-Olivares MJ, López-Maderuelo D, González-Valdés I, Garcia-Izquierdo E, Mingo S, Martín CE, Muiño-Mosquera L, De Backer J, Nistal JF, Forteza A, Evangelista A, Vázquez J, Campanero MR, Redondo JM.Nat Commun. 2021 May 11;12(1):2628. doi: 10.1038/s41467-021-22933-3.PMID: 33976159

Comparability of different Z-score equations for aortic root dimensions in children with Marfan syndrome. Rutten DWE, Aarts-Janssen IJH, Kempers MJE, Reimer AG, Udink Ten Cate FEA, Loeys BL, Slieker MG. Cardiol Young. 2021 Dec;31(12):1962-1968. doi: 10.1017/S1047951121001311. Epub 2021 Apr 12. PMID: 33843540.

Pregnancy outcome in thoracic aortic disease data from the Registry Of Pregnancy And Cardiac disease. Campens L, Baris L, Scott NS, Broberg CS, Bondue A, Jondeau G, Grewal J, Johnson MR, Hall R, De Backer J, Roos-Hesselink JW; ROPAC investigators group. Heart. 2021 Nov;107(21):1704-1709. doi: 10.1136/heartjnl-2020-318183. Epub 2021 Jan 19. PMID: 33468574; PMCID: PMC8522458.

A human importin-β-related disorder: Syndromic thoracic aortic aneurysm caused by bi-allelic loss-of-function variants in IPO8. Van Gucht I, Meester JAN, Bento JR, Bastiaansen M, Bastianen J, Luyckx I, Van Den Heuvel L, Neutel CHG, Guns PJ, Vermont M, Fransen E, Perik MHAM, Velchev JD, Alaerts M, Schepers D, Peeters S, Pintelon I, Almesned A, Ferla MP, Taylor JC, Dallosso AR, Williams M, Evans J; Genomics England Research Consortium, Rosenfeld JA, Sluysmans T, Rodrigues D, Chikermane A, Bharmappanavara G, Vijayakumar K, Mottaghi Moghaddam Shahri H, Hashemi N, Torbati PN, Toosi MB, Al-Hassnan ZN, Vogt J, Revencu N, Maystadt I, Miller EM, Weaver KN, Begtrup A, Houlden H, Murphy D, Maroofian R, Pagnamenta AT, Van Laer L, Loeys BL, Verstraeten A. Am J Hum Genet. 2021 Jun 3;108(6):1115-1125. doi: 10.1016/j.ajhg.2021.04.019. Epub 2021 May 18. PMID: 34010605; PMCID: PMC8206384.

Marfan syndrome. Milewicz DM, Braverman AC, De Backer J, Morris SA, Boileau C, Maumenee IH, Jondeau G, Evangelista A, Pyeritz RE. Nat Rev Dis Primers. 2021 Sep 2;7(1):64. doi: 10.1038/s41572-021-00298-7. Erratum in: Nat Rev Dis Primers. 2022 Jan 17;8(1):3. PMID: 34475413; PMCID: PMC9261969.

*Arrhythmia and impaired myocardial function in heritable thoracic aortic disease: An international retrospective cohort study. Demolder A, Bianco L, Caruana M, Cervi E, Evangelista A, Jondeau G, Buttigieg LL, López-Sainz Á, Delmás EM, Pini A, Sabaté-Rotés A, Szöcs K, Tchitchinadze M, Teixidó-Tura G, von Kodolitsch Y, Muiño-Mosquera L, De Backer J. Eur J Med Genet. 2022 Jun;65(6):104503. doi: 10.1016/j.ejmg.2022.104503. Epub 2022 Apr 12. PMID: 35427808.

* = VASCERN acknowledged

• Year 1: Collaborative Publications

Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome.Byers PH, Belmont J, Black J, De Backer J, Frank M, Jeunemaitre X, Johnson D, Pepin M, Robert L, Sanders L, Wheeldon N.Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):40-47. doi: 10.1002/ajmg.c.31553. Review. PMID: 28306228

The 2017 international classification of the Ehlers-Danlos syndromes.Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, De Backer J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B.Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):8-26. doi: 10.1002/ajmg.c.31552.PMID: 28306229

Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients.Demirdas S, Dulfer E, Robert L, Kempers M, van Beek D, Micha D, van Engelen BG, Hamel B, Schalkwijk J, Loeys B, Maugeri A, Voermans NC.Clin Genet. 2017 Mar;91(3):411-425. doi: 10.1111/cge.12853. Epub 2016 Nov 4.PMID: 27582382

• Year 2 : Collaborative Publications 

Frequency of de novo variants and parental mosaicism in vascular Ehlers-Danlos syndrome. Legrand A, Devriese M, Dupuis-Girod S, Simian C, Venisse A, Mazzella JM, Auribault K, Adham S, Frank M, Albuisson J, Jeunemaitre X. Genet Med. 2018 Nov 26. doi: 10.1038/s41436-018-0356-2. [Epub ahead of print] PMID: 30474650

• Year 3-5 : Collaborative Publications 

Vascular Ehlers-Danlos Syndrome: Long-Term Observational Study. Frank M, Adham S, Seigle S, Legrand A, Mirault T, Henneton P, Albuisson J, Denarié N, Mazzella JM, Mousseaux E, Messas E, Boutouyrie P, Jeunemaitre X. J Am Coll Cardiol. 2019 Apr 23;73(15):1948-1957. doi: 10.1016/j.jacc.2019.01.058. PMID: 30999998.

*Surveillance and monitoring in vascular Ehlers-Danlos syndrome in European Reference Network For Rare Vascular Diseases (VASCERN). van de Laar IMBH, Baas AF, De Backer J, Blankenstein JD, Dulfer E, Helderman-van den Enden ATJM, Houweling AC, Kempers MJ, Loeys B, Malfait F, Robert L, Tanteles G, Frank M. Eur J Med Genet. 2022 Sep;65(9):104557. doi: 10.1016/j.ejmg.2022.104557. Epub 2022 Jun 30. PMID: 35779834.

*Phenotype of COL3A1/COL5A2 deletion patients. Kempers MJ, Wessels M, Van Berendoncks A, van de Laar IM, de Leeuw N, Loeys B. Eur J Med Genet. 2022 Aug 11;65(10):104593. doi: 10.1016/j.ejmg.2022.104593. Epub ahead of print. PMID: 35964930.

* = VASCERN acknowledged

Coming soon!!!

• Year 1: Collaborative Publications 

No collaborative publications from the PPL-WG between March 2017-February 2018.

• Year 2: Collaborative Publications 

No collaborative publications from the PPL-WG between March 2018-February 2019.

• Year 3-4: Collaborative Publications 

Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Fotiou E, Martin-Almedina S, Simpson MA, Lin S, Gordon K, Brice G, Atton G, Jeffery I, Rees DC, Mignot C, Vogt J, Homfray T, Snyder MP, Rockson SG, Jeffery S, Mortimer PS, Mansour S, Ostergaard P. Nat Commun. 2015 Sep 3;6:8085. doi: 10.1038/ncomms9085. Erratum in: Nat Commun. 2019 Apr 26;10(1):1951. PMID: 26333996; PMCID: PMC4568316.

Update and audit of the St George’s classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis. Gordon K, Varney R, Keeley V, Riches K, Jeffery S, Van Zanten M, Mortimer P, Ostergaard P, Mansour S. J Med Genet. 2020 May 14:jmedgenet-2019-106084. doi: 10.1136/jmedgenet-2019-106084. Online ahead of print.PMID: 32409509

Primary lymphoedema. Brouillard P, Witte MH, Erickson RP, Damstra RJ, Becker C, Quéré I, Vikkula M. Nat Rev Dis Primers. 2021 Oct 21;7(1):77. doi: 10.1038/s41572-021-00309-7. PMID: 34675250.

The ICC Compression Questionnaire: A Comprehensive Tool to Evaluate Compression Materials or Devices Applied in Subjects with Lymphedema or Chronic Venous Disease. Devoogdt N, Partsch H, Heroes AK, De Vrieze T, De Groef A, Geraerts I, Damstra RJ, Hafner J, Keeley V, Becker A, Mosti G, Brouwer E, Thomis S. Lymphat Res Biol. 2022 Apr;20(2):191-202. doi: 10.1089/lrb.2020.0125. Epub 2021 Mar 30. PMID: 33781091; PMCID: PMC9081015.

Multicentre clinical trials:

The VASCA-WG currently has one clinical trial underway: The VASE (Vascular Anomaly-Sirolimus Europe) is phase III multicentric study evaluating the efficacy and safety of sirolimus in Vascular Anomalies that are refractory to standard care.

Current Research Studies

• GLA/GSD: Identification of causative genetic mutations. Brussels and Freiburg HCPs involved (started 2016)
• Verrucous Venous Malformation/ Hyperkeratotic Cutaneous Capillary-Venous Malformation (VVM/HCCVM) Genotype to phenotype: Dublin, Freiburg and Brussels HCPs involved (started 2016)
• Identification of novel genes for vascular anomalies: Dublin and Brussels HCPs involved
• VUS characterization using zebrafish: Freiburg and Brussels HCPs involved

Year 1: Collaborative Publications

Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations.Soblet J, Kangas J, Nätynki M, Mendola A, Helaers R, Uebelhoer M, Kaakinen M, Cordisco M, Dompmartin A, Enjolras O, Holden S, Irvine AD, Kangesu L, Léauté-Labrèze C, Lanoel A, Lokmic Z, Maas S, McAleer MA, Penington A, Rieu P, Syed S, van der Vleuten C, Watson R, Fishman SJ, Mulliken JB, Eklund L, Limaye N, Boon LM, Vikkula M. J Invest Dermatol. 2017 Jan;137(1):207-216. doi: 10.1016/j.jid.2016.07.034. Epub 2016 Aug 9. PMID:27519652

Development of an international core outcome set for peripheral vascular malformations: the OVAMA project. Horbach SER, van der Horst CMAM, Blei F, van der Vleuten CJM, Frieden IJ, Richter GT, Tan ST, Muir T, Penington AJ, Boon LM, Spuls PI; OVAMA Consensus Group Br J Dermatol. 2017 Oct 7. doi: 10.1111/bjd.16029. [Epub ahead of print] PMID: 28986976

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling. Amyere M, Revencu N, Helaers R, Pairet E, Baselga E, Cordisco M, Chung W, Dubois J, Lacour JP, Martorell L, Mazereeuw-Hautier J, Pyeritz RE, Amor DJ, Bisdorff A, Blei F, Bombei H, Dompmartin A, Brooks D, Dupont J, González-Enseñat MA, Frieden I, Gérard M, Kvarnung M, Hanson-Kahn AK, Hudgins L, Léauté-Labrèze C, McCuaig C, Metry D, Parent P, Paul C, Petit F, Phan A, Quere I, Salhi A, Turner A, Vabres P, Vicente A, Wargon O, Watanabe S, Weibel L, Wilson A, Willing M, Mulliken JB, Boon LM, Vikkula M. Circulation. 2017 Sep 12;136(11):1037-1048. doi: 10.1161/CIRCULATIONAHA.116.026886. Epub 2017 Jul 7. PMID: 28687708.

Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations. Soblet J, Kangas J, Nätynki M, Mendola A, Helaers R, Uebelhoer M, Kaakinen M, Cordisco M, Dompmartin A, Enjolras O, Holden S, Irvine AD, Kangesu L, Léauté-Labrèze C, Lanoel A, Lokmic Z, Maas S, McAleer MA, Penington A, Rieu P, Syed S, van der Vleuten C, Watson R, Fishman SJ, Mulliken JB, Eklund L, Limaye N, Boon LM, Vikkula M. J Invest Dermatol. 2017 Jan;137(1):207-216. doi: 10.1016/j.jid.2016.07.034. Epub 2016 Aug 9. PMID: 27519652.

Year 2: Collaborative Publications 

No collaborative publications from the VASCA-WG between March 2018-February 2019.

Year 3-5: Collaborative Publications

* RASA1 mosaic mutations in patients with capillary malformation-arteriovenous malformation. Revencu N, Fastre E, Ravoet M, Helaers R, Brouillard P, Bisdorff-Bresson A, Chung CWT, Gerard M, Dvorakova V, Irvine AD, Boon LM, Vikkula M. J Med Genet. 2019 Jul 12. pii: jmedgenet-2019-106024. doi: 10.1136/jmedgenet-2019-106024. [Epub ahead of print] PMID:31300548

*A Clinical Feasibility Study To Image Angiogenesis in Patients With Arteriovenous Malformations Using 68Ga-RGD PET/CT. Lobeek D, Bouwman FCM, Aarntzen EHJG, Molkenboer-Kuenen JDM, Flucke UE, Nguyen HL, Vikkula M, Boon LM, Klein W, Laverman P, Oyen WJG, Boerman OC, Terry SYA, SchultzeKool LJ, Rijpkema M.J Nucl Med. 2019 Sep 13. pii: jnumed.119.231167. doi: 10.2967/jnumed.119.231167. [Epub ahead of print]

The Infantile Hemangioma Referral Score: A Validated Tool for Physicians. Léauté-Labrèze C, Baselga Torres E, Weibel L, Boon LM, El Hachem M, van der Vleuten C, Roessler J, Troilius Rubin A.Pediatrics. 2020 Apr;145(4):e20191628. doi: 10.1542/peds.2019-1628. Epub 2020 Mar 11.PMID: 32161112

New and Emerging Targeted Therapies for Vascular Malformations. Van Damme A, Seront E, Dekeuleneer V, Boon LM, Vikkula M. Am J Clin Dermatol. 2020 Oct;21(5):657-668. doi: 10.1007/s40257-020-00528-w. PMID: 32557381.

*Severe adverse events during sirolimus “off-label” therapy for vascular anomalies.Rössler J, Baselga E, Davila V, Celis V, Diociaiuti A, El Hachem M, Mestre S, Haeberli D, Prokop A, Hanke C, Loichinger W, Quéré I, Baumgartner I, Niemeyer CM, Kapp FG. Pediatr Blood Cancer. 2021 Aug;68(8):e28936. doi: 10.1002/pbc.28936. Epub 2021 Feb 13.PMID: 33580918

*Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network.
Holm A, Te Loo M, Schultze Kool L, Salminen P, Celis V, Baselga E, Duignan S, Dvorakova V, Irvine AD, Boon LM, Vikkula M, Ghaffarpour N, Niemeyer CM, Rössler J, Kapp FG.
Front Pediatr. 2021 Sep 30;9:697960. doi: 10.3389/fped.2021.697960. eCollection 2021.
PMID: 34660476

*Case report study of thalidomide therapy in 18 patients with severe arteriovenous malformations. Boon, L.M., Dekeuleneer, V., Coulie, Marot, L., Bataille, AC., Hammer, F., Clapuyt, P., Jeanjean, A., Dompmartin, A., Vikkula, M. Nat Cardiovasc Res 1, 562–567 (2022). https://doi.org/10.1038/s44161-022-00080-2

*The VASCERN-VASCA working group diagnostic and management pathways for severe and/or rare infantile hemangiomas. Diociaiuti A, Baselga E, Boon LM, Dompmartin A, Dvorakova V, El Hachem M, Gasparella P, Haxhija E, Ghaffarpour N, Kyrklund K, Irvine AD, Kapp FG, Rößler J, Salminen P, van den Bosch C, van der Vleuten C, Kool LS, Vikkula M. Eur J Med Genet. 2022 Jun;65(6):104517. doi: 10.1016/j.ejmg.2022.104517. Epub 2022 Apr 27. PMID: 35487416.

* VASCERN acknowledged