The Vascular Anomalies Working Group (VASCA-WG) is one of the five Rare Disease Working Groups (RDWGs) of VASCERN that specialize in a particular type/group of rare vascular disease(s).

The VASCA-WG is chaired by Professors Miikka VIKKULA and Laurence BOON, from the Centre for Vascular Anomalies at Cliniques Universitaires Saint-Luc in Brussels, Belgium, and Co-Chaired by Professor Leo SCHULTZE KOOL from the Expert Center for Hemangioma and Vascular Anomalies (HECOVAN) at Radboudumc in Nijmegen, Netherlands.

The VASCA-WG cooperates with the European Patient Advocacy Group (ePAG), whose representatives participating in the VASCA-WG are ePAG Co-Chair for VASCA, Caroline VAN DEN BOSCH (HEVAS) and ePAG Deputy Co-Chair Maria BAREA (VASCAPA).

The VASCA-WG members are also active in the International Society of the Study of Vascular Anomalies (ISSVA), which is based in the USA. VASCA-WG members are on the ISSVA scientific committee and the ISSVA Board. Thanks to this, they are part of a major international network with clinicians within the EU and the rest of the world and have been implicated in the identification of most of the genes involved in vascular anomalies and are active in research testing new targeted therapies.

The Center for Vascular Anomalies at Cliniques universitaires Saint-Luc in Brussels Belgium (and other HCP members of the VASCA-WG) takes care of a whole variety of pathologies within the field of Vascular anomalies (see: Wassef et al., Revised classification of Vascular Anomalies, 2015 Pediatrics, and ISSVA web-site).

The Rare Diseases included in this ERN Diseases Working Group are (non exhaustive list):

Bases for the estimated incidence and prevalence numbers: 500 Million inhabitants within European union with about 6 million newborns annually.

sub-thematic areas of expertise	Rare or complex disease(s) or condition(s) or highly specialized interventions	Code/ICD/ Orphacode / Group of Codes	Incidence (Number of cases / year) (in the EU)	Prevalence (in the EU)
VASCA	Rare arteriovenous malformation	ORPHA211266	120	10000
VASCA	Blue Rubber Bleb Nevus syndrome	ORPHA1059	6	500
VASCA	Capillary malformation-arteriovenous malformation	ORPHA137667	120	10000
VASCA	Cerebral arteriovenous malformation	ORPHA46724
VASCA	CLAPO syndrome	ORPHA168984
VASCA	CLOVES syndrome	ORPHA140944	60	5000
VASCA	Cutis Marmorata Telangiectatica Congenita	ORPHA1556	12	1000
VASCA	Diffuse neonatal hemangiomatosis	ORPHA2123
VASCA	Facial arteriovenous malformation	ORPHA156230
VASCA	Familial cerebral cavernous malformation	ORPHA221061	600	50000
VASCA	Diffuse lymphatic anomaly	ORPHA141209
VASCA	Glomuvenous malformation	ORPHA83454	30	2500
VASCA	Gorham-Stout syndrome	ORPHA73	6	500
VASCA	Infantile hemangioma of rare localization	ORPHA210589
VASCA	Kaposiform hemangioendothelioma	ORPHA2122
VASCA	Klippel-Trénaunay-Weber syndrome	ORPHA2346	60	5000
VASCA	LUMBAR association	ORPHA83628
VASCA	Rare lymphatic malformation	ORPHA2415	600	50000
VASCA	Megalencephaly-capillary malformation-polymicrogyria syndrome	ORPHA60040	12	1000
VASCA	Macrocystic lymphatic malformation	ORPHA79489
VASCA	Maffucci syndrome	ORPHA163634	6	500
VASCA	Microcystic lymphatic malformation	ORPHA79490
VASCA	Mixed cystic lymphatic malformation	ORPHA458792
VASCA	Mucocutaneous venous malformation	ORPHA2451
VASCA	Non-involuting congenital hemangioma	ORPHA141179	20	500
VASCA	Primary intralymphatic angioendothelioma	ORPHA458768
VASCA	Parkes-Weber syndrome	ORPHA90307	30	2500
VASCA	Partially-involuting congenital hemangioma	ORPHA458785
VASCA	PHACE syndrome	ORPHA42775
VASCA	Proteus syndrome	ORPHA744	6	500
VASCA	PTEN hamartoma tumor syndrome	ORPHA306498	30	2500
VASCA	Pulmonary arteriovenous malformation	ORPHA2038
VASCA	Rapidly involuting congenital hemangioma	ORPHA141184	60	5000
VASCA	Rare capillary malformation	ORPHA211247	60	5000
VASCA	SACRAL association	ORPHA2125
VASCA	Spindle cell hemangioma	ORPHA210584
VASCA	Sturge-Weber syndrome	ORPHA3205	120	10000
VASCA	Tufted angioma	ORPHA1063	3	250
VASCA	Rare venous malformation	ORPHA211252	1200	100000
VASCA	Verrucous hemangioma	ORPHA464318

All HCP in the VASCA-WG are covering this sub-thematic area of expertise.

In this ERN, there is a specific WG for Pediatric and Primary Lymphedemas.

Hereditary hemorrhagic telangiectasia (HHT, orphanet: 774, ICD‐10: I78.0) is also a vascular anomaly, but for historical reasons specialised centers have been build up for that single diseases on the past. HHT is included as a separate WG within the ERN (see HHT WG).

Pills of Knowledge (PoK)

Pills of Knowledge (PoK) are the deliverable for VASCERN Work Package 4 on Pills of Knowledge, defined as short single video lessons (of approximately 3-5 minutes long) in which an expert talks about a specific topic that has been selected and validated by the Rare Disease Working Groups (RDWGs).

Link to the playlist for the VASCA-WG on our YouTube Channel is here

Classification of Vascular Anomalies

Created by Prof. Laurence Boon (Plastic Surgeon, Coordinator of the Center for Vascular Anomalies, Cliniques Universitaires St Luc, Brussels, Belgium).

This Pill of Knowledge (PoK) gives a brief overview of the classification of vascular anomalies. It is intended for the medical community who is not familiar with these anomalies as it introduces the main types of vascular anomalies and their characteristics.

Video in English. Subtitles available in 8 European languages (English, Dutch, Finnish, French, German, Italian, Spanish and Swedish).

Diagnostic Approaches for Vascular Anomalies

Created by Dr. Friedrich Kapp (Physician Scientist, University Medical Center, Freiburg, Germany).

This Pill of Knowledge (PoK) talks about the diagnostic approaches for vascular anomalies. The various types of examination and tests involved in reaching an appropriate diagnosis are described. This PoK is a valuable tool for healthcare professionals and patients wanting to learn more about how vascular anomalies are diagnosed.

Video in English. Subtitles available in 8 European languages (English, Dutch, Finnish, French, German, Italian, Spanish and Swedish).

Multi-disciplinary Expertise Teams for Vascular Anomalies

Created by Prof. Leo Schultze Kool (Interventional Radiologist, Radboud University Medical Center, Nijmegen, Netherlands).

This Pill of knowledge (PoK) gives a brief summary of why multi-disciplinary expert teams are so necessary for the management and treatment of vascular anomalies. It is intended for the general public.

Video in English. Subtitles available in 8 European languages (English, Dutch, Finnish, French, German, Italian, Spanish and Swedish).

Management of Vascular Anomalies

Created by Dr. Kristiina Kyrklund (Pediatric Surgeon, Helsinki University Hospital, Helsinki, Finland)

In this Pill of Knowledge (PoK) Dr. Kristiina Kyrklund gives an introduction on the individualized management of vascular anomalies and how the chosen treatment is based on the characteristic symptoms and location of the anomaly. Suitable for both healthcare professsionals and patients.

Video in English. Subtitles available in 8 European languages (English, Dutch, Finnish, French, German, Italian, Spanish and Swedish).

The lymphatic system & lymphatic malformations (Lymfestelsel en lymfatische malformaties) – video in Dutch

This video, produced by the patient organisation HEVAS and validated by the VASCA-WG, talks about the lymphatic system and lymphatic malformations. This video has been made for patients and introduces the patient organisation HEVAS and their work.

View this video here

This video is now available in English (see below).

Treatments for lymphatic malformations (Behandelingen voor lymfatische malformaties) – video in Dutch

This video, produced by the patient organisation HEVAS and validated by the VASCA-WG, describes the treatments currently available for lymphatic malformations in a clear and understandable manner suited for patients.

View this video here

This video is now available in English (see below).

The lymphatic system & lymphatic malformations

This PoK video (produced by the patient organisation HEVAS and revised and validated by the VASCA-WG) gives an introduction on the lymphatic system and lymphatic malformations. It is intended for patients and the general public and uses simple language to explain the various medical terms discussed.

Video in English. Subtitles are currently available in 7 European languages (English, Dutch, French, German, Italian, Spanish and Swedish).

View this video here

Treatment of lymphatic malformations

This PoK video (produced by the patient organisation HEVAS and revised and validated by the VASCA-WG) presents the various treatment options for lymphatic malformations. It is intended for patients and the general public and uses simple language to explain the various medical terms and procedures discussed.

Video in English. Subtitles are currently available in 7 European languages (English, Dutch, French, German, Italian, Spanish and Swedish).

View this video here

Klippel-Trenaunay syndrome (KTS)

This PoK video, produced by the patient organisation HEVAS and validated by the VASCA-WG, gives an introduction to Klippel-Trenaunay syndrome (KTS), a congenital vascular bone syndrome. It is intended for patients and the general public and uses simple language to explain the clinical characteristics of this rare disease.

Video in English. Subtitles are currently available in 7 European languages (English, Dutch, French, German, Italian, Spanish and Swedish).

View this video here

The PIK3CA gene and related vascular malformations

This short PoK video explains how an error in the PIK3CA gene can be the cause of congenital vascular malformations, such as lymphatic and venous malformations, which can be isolated or occur in overgrowth syndromes. Diagnosis and treatment are also briefly covered.

It is intended for patients and the general public and uses simple language to introduce PIK3CA related vascular abnormalities, which includes the complex group of disorders known as PROS (PIK3CA-Related Overgrowth Spectrum).

Created by the patient organisation HEVAS (the Dutch Patient organisation for hemangioma and vascular malformations), this PoK was then revised and validated by VASCERN’s Vascular Anomalies Working Group (VASCA-WG).

Video in English with subtitles in English.

View this video here.

Webinars

VASCERN Webinar: Classification of vascular anomalies

This webinar consists of a scientific presentation followed by a Q&A session.

Featuring Vascular Anomalies Working Group (VASCA-WG) members: Prof. Miikka Vikkula, Prof. Emir Haxhija and Dr. Paolo Gasparella.

Video in English.

VASCERN Webinar: Diagnostic and Management Pathway for Severe and/or Rare Infantile Hemangiomas.

This webinar consists of a scientific presentation followed by a Q&A session.

Featuring Vascular Anomalies Working Group (VASCA-WG) member: Prof Andrea Diociaiuti.

Video in English.

VASCERN Webinar: Diagnostic and Management Pathway for Venous Malformations.

This webinar consists of a scientific presentation followed by a Q&A session.

Featuring Vascular Anomalies Working Group (VASCA-WG) member: Prof. Laurence Boon.

Video in English.

VASCERN Webinar: Diagnostic and Management Pathway for Lymphatic Malformations.

This webinar consists of a scientific presentation followed by a Q&A session.

Featuring Vascular Anomalies Working Group (VASCA-WG) member: Dr Nader Ghaffarpour.

Video in English.

Patient Pathways aim to improve the care and management of patients with a rare disease. They include the “red flags” that may lead to the suspicion of the disease, how to reach a definite diagnosis and the management and follow-up recommendations. They are a very important tool used in defining the best patient care and will be further validated and updated when needed.

 

The first Patient Pathway by the VASCA-WG on Severe/Rare Infantile Hemangioma (issued 20/03/2019) can be found here

 

 

 

 

German translation here

Italian translation here

Spanish translation here

Swedish translation here

 

The Capillary Malformation Patient Pathway (issued 29/04/2020) can be found here

 

 

 

 

 

 

The Venous Malformation Patient Pathway (issued 29/04/2020) can be found here

 

 

 

 

 

 

 

The Lymphatic Malformation Patient Pathway (issued 29/04/2020) can be found here

 

 

1. Wassef M, Blei F, Adams D, Alomari A, Baselga E, Berenstein A, Burrows P, Frieden IJ, Garzon MC, Lopez-Gutierrez JC, Lord DJ, Mitchel S, Powell J, Prendiville J, Vikkula M; ISSVA Board and Scientific Committee. Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies. Pediatrics. 2015 Jul;136(1):e203-14. doi: 10.1542/peds.2014-3673. Epub 2015 Jun 8. Review.
2. On the ISSVA web-site, the classification is available with more detailed genetic data: here
3. Stillo et al. Vascular Anomalies Guidelines by the Italian Society for the Study of Vascular Anomalies (SISAV). Angiology, volume 34. April 2015, Suppl 1 to issue No. 2. (These guidelines will be discussed within the VASCA-WG for further development so as to establish first European guidelines).
4. A. Elajmi, P. Clapuyt, F. Hammer, A.-C. Bataille, B. Lengele, L.M. Boon. Prise en charge des anomalies vasculaires chez l’enfant. Management of vascular anomalies in children. Annales de chirurgie plastique esthétique (2016). (These guidelines will be discussed within the VASCA-WG for further development so as to establish first European guidelines).

The VASCA-WG will also be working in tight collaboration with ISSVA, which is setting up working groups for establishment of best practice guidelines for various vascular anomalies.

VASCERN Vascular Anomalies (VASCA) Working Group COVID-19 Statement (March 20, 2020)– initiated by the patient advocacy groups in Europe and the United States and their medical advisory teams and approved by the VASCA WG.

This statement can equally be found in:

French: Information COVID-19 pour les patients porteurs d’ Anomalies Vasculaires et/ou Lymphatiques

Finnish: VASCERN Suonipoikkeavuuksien (VASCA) työryhmä – Tietoa koronaviruksesta (COVID-19) potilaille, joilla on vaikea suonipoikkeavuus

 VASCERN Vascular Anomalies (VASCA) Working Group – Statement concerning SARS-CoV-2 Vaccination for Patients with Vascular Malformations

The VASCA-WG is currently working on creating other expert consensus statement documents on various rare vascular anomalies.

The VASCA-WG is currently working on defining their clinical outcome measures. They are involved in/actively following the ongoing OVAMA (Outcome Measures for Vascular Malformations) project.

The VASCA-WG is currently working on their Do’s and Don’ts Factsheets.

The VASCA Registry project consists of the creation of a FAIR registry dedicated to the diseases covered by the VASCA-WG. It has been designed to include the European core dataset as well as set of data specific to the rare diseases of VASCA.

More information on the Registry WG page here.

The VASCA-WG equally endorses the SECURE-VA registry, which aims to report the COVID-19 cases in Vascular Anomalies (VA) patients globally, in both children and adults.

 

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