Research Publications

This article offers comprehensive guidelines for improving genetic testing in vascular malformations. Despite advancements, access to genetic testing is limited, and inconsistent methods impact test accuracy. This study, involving experts from 11 European centers, reviews genes linked to non-hereditary vascular malformations, evaluates gene-disease associations, and provides recommendations for identifying mosaicism and interpreting variants. A core list of 24 genes was selected, with 45 gene-phenotype associations evaluated. The findings emphasize the importance of understanding gene-phenotype relationships to improve diagnostics and patient care.

De Bortoli M, Ivars M, Revencu N, Nassogne MC, Lavarino C, Paco S, Lammens M, Renders A, Dumitriu D, Helaers R, Boon LM, Baselga E, Vikkula M. Epilepsy with faint capillary malformation or reticulated telangiectasia associated with mosaic AKT3 pathogenic variants. Am J Med Genet A. 2024 Feb 6:e63551. doi: 10.1002/ajmg.a.63551. Epub ahead of print. PMID: 38321651.

Seront E, Van Damme A, Legrand C, Bisdorff-Bresson A, Orcel P, Funck-Brentano T, Sevestre MA, Dompmartin A, Quere I, Brouillard P, Revencu N, De Bortoli M, Hammer F, Clapuyt P, Dumitriu D, Vikkula M, Boon LM. Preliminary results of the European multicentric phase III trial regarding sirolimus in slow-flow vascular malformations. JCI Insight. 2023 Nov 8;8(21):e173095. doi: 10.1172/jci.insight.173095. PMID: 37937645.

Bouwman FCM, Verhaak C, de Blaauw I, Kool LJS, Loo DMWMT, van Rooij IALM, van der Vleuten CJM, Botden SMBI, Verhoeven BH. Health-related quality of life in children with congenital vascular malformations. Eur J Pediatr. 2023 Nov;182(11):5067-5077. doi: 10.1007/s00431-023-05166-y. Epub 2023 Sep 4. PMID: 37665335; PMCID: PMC10640403.

Gasparella P, Senica SO, Singer G, Banfi C, Flucher C, Beqo BP, Till H, Haxhija EQ. Pediatric vascular anomalies in Austria. Where are we at? A survey among primary care pediatricians. Front Pediatr. 2023 Aug 17;11:1216460. doi: 10.3389/fped.2023.1216460. PMID: 37664549; PMCID: PMC10473968.

Seront E, Biard J.M, Van Damme A, Revencu N, Lengelé B, Schmitz S, de Toeuf C, Clapuyt P, Veyckemans F, Prégardien C, Vikkula M, Bernard P, Boon Laurence M. A case report of sirolimus use in early fetal management of lymphatic malformation. Nat Cardiovasc Res (2023). https://doi.org/10.1038/s44161-023-00280-4

Harbers VEM, Bouwman FCM, van Rijnsoever IMP, Verhoeven BH, van der Vleuten CJM, Schultze Kool LJ, de Laat PCJ, van der Horst CMAM, Kievit W, Te Loo DMWM. Magnitude and relevance of change in health-related quality of life in patients with vascular malformations treated with sirolimus. Front Med (Lausanne). 2023 Apr 20;10:1155476. doi: 10.3389/fmed.2023.1155476. PMID: 37153086; PMCID: PMC10157393.

Tuleja A, Bernhard S, Hamvas G, Andreoti TA, Rössler J, Boon L, Vikkula M, Kammer R, Haupt F, Döring Y, Baumgartner I. Clinical phenotype of adolescent and adult patients with extracranial vascular malformation. J Vasc Surg Venous Lymphat Disord. 2023 Sep;11(5):1034-1044.e3. doi: 10.1016/j.jvsv.2023.03.012. Epub 2023 Apr 6. PMID: 37030445.

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. RASA1 mosaic mutations in patients with capillary malformation-arteriovenous malformation. J Med Genet. 2020 Jan;57(1):48-52. doi: 10.1136/jmedgenet-2019-106024. Epub 2019 Jul 12. PMID: 31300548.

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. Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling. Circulation. 2017 Sep 12;136(11):1037-1048. doi: 10.1161/CIRCULATIONAHA.116.026886. Epub 2017 Jul 7. PMID: 28687708.

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. Development of an international core outcome set for peripheral vascular malformations: the OVAMA project. Br J Dermatol. 2018 Feb;178(2):473-481. doi: 10.1111/bjd.16029. Epub 2018 Jan 19. PMID: 28986976.

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. Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations. J Invest Dermatol. 2017 Jan;137(1):207-216. doi: 10.1016/j.jid.2016.07.034. Epub 2016 Aug 9. PMID: 27519652.

Dompmartin, A., Baselga, E., Boon, L. M., Diociaiuti, A., Dvorakova, V., El Hachem, M., Gasparella, P., Haxhija, E., Ghaffarpour, N., Kyrklund, K., Irvine, A. D., Kapp, F. G., Rößler, J., Salminen, P., van den Bosch, C., van der Vleuten, C., Schultze Kool, L., & Vikkula, M. (2023). The VASCERN-VASCA Working Group Diagnostic and Management Pathways for Venous Malformations. Journal of vascular anomalies, 4(2), e064. https://doi.org/10.1097/JOVA.0000000000000064

Gasparella P, Flucher C, Beqo BP, Schmidt B, Spendel S, Arneitz C, Till H, Haxhija EQ, Singer G. Outcome after surgical treatment of venous malformations of the hand in childhood. J Vasc Surg Venous Lymphat Disord. 2023 Jul;11(4):793-800. doi: 10.1016/j.jvsv.2023.02.004. Epub 2023 Mar 10. PMID: 36906103.

Harbers VEM, Zwerink LGJM, Rongen GA, Klein WM, van der Vleuten CJM, van Rijnsoever IMP, Gerdsen-Drury L, Flucke UE, Verhoeven BH, de Laat PCJ, van der Horst CMAM, Schultze Kool LJ, Te Loo DMWM. Clinical differences in sirolimus treatment with low target levels between children and adults with vascular malformations – A nationwide trial. Clin Transl Sci. 2023 May;16(5):781-796. doi: 10.1111/cts.13488. Epub 2023 Feb 23. PMID: 36824030; PMCID: PMC10176016.

Andreoti TA, Berg S, Holm A, Angerer M, Oberlin M, Foeldi E, Baumgartner I, Niemeyer CM, Rössler J, Kapp FG. Complex Lymphatic Anomalies: Report on a Patient Registry Using the Latest Diagnostic Guidelines. Lymphat Res Biol. 2023 Jun;21(3):230-243. doi: 10.1089/lrb.2022.0041. Epub 2023 Jan 27. PMID: 36706428.

Ghaffarpour, N., Baselga, E., Boon, L. M., Diociaiuti, A., Dompmartin, A., Dvorakova, V., El Hachem, M., Gasparella, P., Haxhija, E., Kyrklund, K., Irvine, A. D., Kapp, F. G., Rößler, J., Salminen, P., van den Bosch, C., van der Vleuten, C., Kool, L. S., & Vikkula, M. (2022). The VASCERN-VASCA working group diagnostic and management pathways for lymphatic malformations. European journal of medical genetics, 65(12), 104637. https://doi.org/10.1016/j.ejmg.2022.104637

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

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. The VASCERN-VASCA working group diagnostic and management pathways for severe and/or rare infantile hemangiomas. Eur J Med Genet. 2022 Jun;65(6):104517. doi: 10.1016/j.ejmg.2022.104517. Epub 2022 Apr 27. PMID: 35487416.

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. Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network. Front Pediatr. 2021 Sep 30;9:697960. doi: 10.3389/fped.2021.697960. PMID: 34660476; PMCID: PMC8515018.

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. Severe adverse events during sirolimus “off-label” therapy for vascular anomalies. Pediatr Blood Cancer. 2021 Aug;68(8):e28936. doi: 10.1002/pbc.28936. Epub 2021 Feb 13. PMID: 33580918.

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

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

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, Schultze Kool LJ, Rijpkema M. A Clinical Feasibility Study to Image Angiogenesis in Patients with Arteriovenous Malformations Using ⁶⁸Ga-RGD PET/CT. J Nucl Med. 2020 Feb;61(2):270-275. doi: 10.2967/jnumed.119.231167. Epub 2019 Sep 13. PMID: 31519800; PMCID: PMC7100027.