The PPL Working Group, is built upon Multidisciplinary Centres of Excellence collaborating and have a long-standing expertise in the diagnosis and management of adults and children with lymphatic problems


The PPL-WG is chaired by Dr. Robert Damstra, Dermatologist at the Expert center for lympho-vascular medicine, Nij Smellinghe hospital, Drachten, Netherlands. This WG is co-chaired by Prof. Sahar Mansour, and Prof. Peter Mortimer, Paediatric and Primary Lymphoedema Clinic, St George’s University Hospitals NHS Foundation Trust, London, UK. These chairs, and the Working Group, have a long-standing expertise in the diagnosis and management of adults and children with lymphatic problems. The PPL-WG cooperates with the Patient-WG.

The lymphatic system is arguably the most neglected bodily system, and as a result, its contribution to human health and disease is not well understood. Lymphatic impairment can be either due to an overload of the lymphatic system (high preload) or a failure / lowered transport capacity (low afterload) (primary lymphedema). Primary lymphedema is highly heterogeneous. In-depth phenotyping has led to the identification of several new conditions and genetic causes. Our group have published a classification and diagnostic algorithm (Connell et al, 2013) to assist in making an accurate diagnosis.
Accurate diagnosis and a multi-disciplinary approach to management are mandatory for this chronic condition with a high morbidity.
Secondary lymphedema is relatively common (as a complication of malignancy, surgery or infection). Many guidelines do not specifically discriminate between primary and secondary lymphedema or the dedicated treatment of children with primary lymphedema.
A dedicated approach towards primary lymphedema, and any lymphoedema in a child, needs specialized centers of expertise.
The PPL-WG will interact with all the other WGs within this ERN, especially the Vascular Anomalies WG (VASCA-WG), particularly with regard to some lymphovascular disorders, which may present with lymphedema of the extremities.

The treatment of lymphedema needs an interdisciplinary, holistic approach. As a chronic condition, the patient should be educated in self-management and awareness.

In 2001, the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) was introduced. It can be used to assess the benefits of the management and treatments for all chronic diseases. It provides an appropriate framework that allows systematic categorization of clinical observations based on an integrated bio-psycho-social model. This model focuses, not just on physical and medical aspects, but takes also social functioning, personal and environmental aspects into account. The ICF framework consists of the following components:
– Body structures and functions
– Activities and participations
– Personal and environmental factors
By using the ICF method for evaluation of the results of treatment, the focus is not just on volume of the limb but includes a more holistic approach and takes the whole patient and daily practice functioning into account. Special core set for lymphedema have been developed(4) and needs further implementation.

The International Lymphedema Framework (ILF) camp for children presents two videos:

– Highlights of the children camps, which is going to be replicated this year in Italy
– Children explaining what it means living with Lymphoedema 

Main Thematic Group: primary lymphedemas including syndromic lymphedema in children and adults, and lymphovascular disorders. Secondary lymphedema in children up to 18 years of age.

Related Rare Or Complex Disease(s):
Lymphedema (ORPHA79383)

Congenital Lymphedema
– Milroy syndrome (ORPHA79452)

Late onset lymphedema
– Meige syndrome (ORPHA90186)
– Lymphedema distichiasis syndrome (ORPHA33001)
– Emberger syndrome (ORPHA3226)

Lymphedema with systemic involvement
– Hennekam syndrome (ORPHA2136)
– PIEZO1 related lymphatic dysplasia
– Generalised lymphatic dysplasia
– Multi-systemic lymphedema with systemic involvement

Syndromes associated with lymphedema
– Noonan/CFC syndrome (RASOpathies) (ORPHA648)
– Turner syndrome (ORPHA881)
– 22q13 microdeletion (ORPHA48652)
– Microcephaly with or without Chorioretinopathy, Lymphedema and Mental Retardation (MCLMR)(ORPHA2526)

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

sub-thematic areas of expertiseRare or complex disease(s) or condition(s) or highly specialized interventionsCode/ICD/ Orphacode / Group of CodesIncidence (Number of cases / year)Prevalence (in the EU)
PPLAnhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndromeORPHA69088  
PPLCholestasis-lymphedema syndromeORPHA1414  
PPLDahlberg-Borer-Newcomer syndromeORPHA1563  
PPLDeafness-lymphedema-leukemia syndromeORPHA3226 
PPLGenetic primary lymphedemaORPHA459530
PPLHennekam syndromeORPHA2136
PPLHypotrichosis-lymphedema-telangiectasia-renal defect syndromeORPHA69735
600prevalence of primary lymphedema is unknown, but is approximately 50 000
PPLLymphedema-atrial septal defects-facial changes syndrome ORPHA86915
PPLLymphedema-cerebral arteriovenous anomaly syndrome ORPHA86914
PPLLymphedema-distichiasis syndrome ORPHA33001
PPLLymphedema-posterior choanal atresia syndromeORPHA99141
PPLMacrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndromeORPHA487796
PPLMeige diseaseORPHA90186
PPLMicrocephaly-lymphedema-chorioretinopathy syndromeORPHA2526
PPLMilroy diseaseORPHA79452 
PPLMonosomy 22q13ORPHA48652 
PPLNon-hereditary late-onset primary lymphedemaORPHA90185 
PPLNoonan syndromeORPHA648 
PPLNoonan syndrome and Noonan-related syndromeORPHA98733
PPLNoonan syndrome with multiple lentiginesORPHA500
PPLNoonan syndrome-like disorder with juvenile myelomonocytic leukemiaORPHA363972
PPLNoonan syndrome-like disorder with loose anagen hairORPHA2701  
PPLPrimary lymphedemaORPHA77240 
PPLPrimary lymphedema with associated anomaliesORPHA458841  
PPLSegmental progressive overgrowth syndrome with fibroadipose hyperplasiaORPHA314662 
PPLSyndromic lymphedemaORPHA89832
PPLTurner syndrome ORPHA881 
PPLTurner syndrome due to structural X chromosome anomaliesORPHA99413  
PPLYellow nail syndromeORPHA662  
All HCP in the PPL-WG are covering this sub-thematic area of expertise.




Nij Smellinghe hospital, Drachten, The Netherlands

VASCERN PPL European Reference Centre, Expert Center for lymphovascular medecine


Dr. Robert J. DAMSTRA


Dr. Kirsten VAN DUINEN





 St George’s University Hospitals, London, UK

VASCERN PPL European Reference Centre, Primary and Paediatric lymphedema clinic, Dermatology and Clinical Genetics


Prof. Sahar MANSOUR
Consultant and Honorary Professor in Clinical Genetics


Dr. Kristiana GORDON
Consultant in Dermatology & Lymphovascular Medicine



Derby Teaching Hospitals NHSF Trust, Derby, UK

VASCERN PPL European Reference Centre, Paediatric and Primary Lymphedema Department


Dr. Vaughan KEELEY
Lymphoedema Consultant


Senior Research Nurse
Lymphoedema and Palliative Medicine






AZ Sint-Maarten , Mechelen, Belgium

VASCERN PPL European Reference Centre, Lymphedema Centre


Vascular Surgeon


Dr. Florence BELVA
Vascular Surgeon




University Hospitals Leuven, Leuven, Belgium

VASCERN PPL European Reference Centre, Lymphovenous Center


Dr. Sarah THOMIS
Vascular Surgeon








ePAG Co-Chair




Helsinki University Hospital, Helsinki, Finland

VASCERN PPL European Reference Centre, Department of Plastic Surgery


Pr. Sinikka SUOMINEN 
Plastic Surgeon


Plastic Surgeon






Consortium: AP-HP, HEGP Hôpital européen Georges Pompidou, Paris, France

VASCERN PPL European Reference Centre, French Reference Center rare vascular diseases, Primary Lymphedema Unit, Hôpital Cognacq-Jay


Dr. Stéphane VIGNES
Specialist in Internal Medecine Lymphology







Consortium: University Medical Center Freiburg and Földi Clinic, Merzhausen, Germany

VASCERN PPL European Reference Centre, European Centre for Lymphology


Dr. Michael OBERLIN
Specialist in internal medicine
Wound Management / Lymphology


Prof. Jochen RÖßLER
Pediatric Hematology/Oncology






ePAG Deputy Co-Chair




There are 2 types of affiliated partners:

  1. Associated National Centres (mainly healthcare providers) for those ERNs where an EU Member State is not yet represented by a full member in the respective ERN. It establishes a link with one specific ERN.
  2. A National Coordination Hub which establishes at once a link with more than one Network in which a given Member State is neither represented by a full member nor by an Associated National Centre. National Coordination Hubs may especially represent a useful solution for those Member States with very small populations that need to establish such links with many ERNs at once.

Associated National Centers



University Medical Centre Ljubljana, Ljubljana, Slovenia

Dermatovenereological clinic



Our PPL-WG Goals are to:

  • implement a data privacy compliant registry to collect data on Paediatric and Primary lymphedema
  • provide highly specialised healthcare for this rare and complex group of disorders
  • establish clear patient pathways
  • evaluate and implement solutions to use information and communication technology (ICT) to provide patient-centered treatment and care
  • establish clinical guidelines for the disorders within our workgroup
  • implement quality improvement programs
  • collaborative research on the diseases within our workgroup


Damstra RJ, Halk A-B. The Dutch lymphedema guidelines based on the International Classification of Functioning, Disability, and Health and the chronic care model, Journal of Vascular Surgery, 5 (2017) 756-765. doi:10.1016/j.jvsv.2017.04.012 (contains condensed summary from Dutch 2015 Lymphedema Guidelines)


German guidline “Diagnostis and therapy of lymphedema“: Jörg Wilting, Rolf Bartkowski, Rüdiger Baumeister, Etelka Földi, Susanna Stöhr, Gerson Strubel, Klaus Schrader, Jürg Traber, S2k Leitlinie – Diagnostik und Therapie der Lymphödeme AWMF Reg.-Nr. 058-001, May 2017

English version of German Guidelines “Diagnostics and therapy of lymphedema” available here

Report of German Guidelines with all the collaborating members from Germany, Austria and Switzerland

The German guidelines are published here (organised by by 32 different groups in Germany, Austria and Switzerland).


The Children’s Lymphoedema Special Interest Group (CLSIG) has produced a Children’s Charter.

Charter of Care for Children and Young People with Lymphoedema

CLSIG Childhood Lymphoedema Diagnostic and Assessment pathways

St. George’s Paediatric Investigation Tool for patients with primary lymphoedema

Classification and Diagnostic Algorithm for Primary Lymphatic Dysplasia

Supporting documents and clinic information are available here


The PNDS (French National Protocol for care in Rare Disease) for PPL

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 General Patient Pathway for Pediatric and Primary Lymphedema (PPL) ( issued 08/11/2019) can be found here






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).

All Pills of Knowledge by the Pediatric and Primary Lymphedema Working Group (PPL-WG) can be found in the PPL-WG Playlist here

An Overview of Pediatric and Primary Lymphedema

The video introduces the lymphatic system and gives a brief summary on what exactly is lymphedema. Diagnosis, treatment, and complications are all explained in a clear and understandeable manner, making this video accessible to patients and the general public.

Video in English. Subtitles available in 5 European languages (English, French, Dutch, German and Finnish).

View this video here

Compression in Pediatric and Primary Lymphedema

Created by Dr. Kirsten F. van Duinen (Dermatologist, Nij Smellinghe Hospital Drachten, Netherlands)

This Pill of Knowledge (PoK) introduces the therapeutic process involved in the treatment of Pediatric and Primary Lymphedema (PPL) and how compression therapy is the cornerstone of management and treatment in PPL. It is intended for healthcare professionals and patients who would like to know more about the different types of compression therapy used to manage PPL.

Video in English. Subtitles available in 4 European languages (Dutch, English, French and German).

Cellulitis / Erysipelas in Pediatric and Primary Lymphedema

Created by Dr. Vaughan Keeley (Lymphedema Consultant, Derby Teaching Hospitals NHSF Trust, Derby, UK)

In this Pill of Knowledge (PoK), Dr. Vaughan Keeley gives an overview of cellulitis/erysipelas, which is a bacterial infection and a common complication in patients with Pediatric and Primary Lymphedema (PPL). He reviews the clinical presentation, diagnosis and treatment for cellulitis. This PoK is suitable for both patients and healthcare professionals.

Video in English. Subtitles available in 4 European languages (English, French, Dutch and German).

Lymphedema from a child’s perspective

Created by andLINFA (The National Association of Sufferers of Lymphatic Disorders – Portugal) and validated by members of the Pediatric and Primary Lymphedema Working Group (PPL WG).

In this Pill of Knowledge (PoK), Leonor, a Portuguese girl with lymphedema gives her testimonial of what it is like to live with this rare disease. It is suitable for both children and adults and a great resource for raising awareness of PPL.

Video is in Portuguese but subtitles are available in 9 European languages (Portuguese, English, Danish, Swedish, Dutch, Italian, Spanish, German and French).

The PPL WG Registry project will consist of the creation of a FAIR registry dedicated to the diseases covered by the PPL WG, with the same aims, organisation and steps as the VASCA Registry. In addition, the PPL working group will benefit from the progress made by the VASCA working group, as PPL will use the same server, program, and development strategy as VASCA.

More information on the Registry WG page here.

– 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. Novel mutations in PIEZO1 cause an
autosomal recessive generalized lymphatic dysplasia with non-immune hydrops
fetalis. Nat Commun. 2015 Sep 3;6:8085.

– Joyce S, Gordon K, Brice G, Ostergaard P, Nagaraja R, Short J, Moore S,
Mortimer P, Mansour S. The lymphatic phenotype in Noonan and Cardiofaciocutaneous syndrome. Eur J Hum Genet. 2015 Aug 5.

– Atton G, Gordon K, Brice G, Keeley V, Riches K, Ostergaard P, Mortimer P,
Mansour S. The lymphatic phenotype in Turner syndrome: an evaluation of nineteen
patients and literature review. Eur J Hum Genet. 2015 Dec;23(12):1634-9.

– Hanson HL, Wilson MJ, Short JP, Chioza BA, Crosby AH, Nash RM, Marks KJ,
Mansour S. Germline CBL mutation associated with a noonan-like syndrome with
primary lymphedema and teratoma associated with acquired uniparental isodisomy of chromosome 11q23. Am J Med Genet A. 2014 Jan 23.

– Jones GE, Ostergaard P, Moore AT, Connell FC, Williams D, Quarrell O, Brady
AF, Spier I, Hazan F, Moldovan O, Wieczorek D, Mikat B, Petit F, Coubes C, Saul
RA, Brice G, Gordon K, Jeffery S, Mortimer PS, Vasudevan PC, Mansour S.
Microcephaly with or without chorioretinopathy, lymphoedema, or mental
retardation (MCLMR): review of phenotype associated with KIF11 mutations. Eur J
Hum Genet. 2013 Nov 27.

– Connell FC, Gordon K, Brice G, Keeley V, Jeffery S, Mortimer PS, Mansour S,
Ostergaard P. The classification and diagnostic algorithm for primary lymphatic
dysplasia: an update from 2010 to include molecular findings. Clin Genet. 2013

– Gordon K, Schulte D, Brice G, Simpson MA, Roukens MG, van Impel A, Connell F,
Kalidas K, Jeffery S, Mortimer PS, Mansour S, Schulte-Merker S, Ostergaard P.
Mutation in vascular endothelial growth factor-C, a ligand for vascular
endothelial growth factor receptor-3, is associated with autosomal dominant
milroy-like primary lymphedema. Circ Res. 2013 Mar 15;112(6):956-60.

– Ostergaard P, Simpson MA, Mendola A, Vasudevan P, Connell FC, van Impel A,
Moore AT, Loeys BL, Ghalamkarpour A, Onoufriadis A, Martinez-Corral I, Devery S,
Leroy JG, van Laer L, Singer A, Bialer MG, McEntagart M, Quarrell O, Brice G,
Trembath RC, Schulte-Merker S, Makinen T, Vikkula M, Mortimer PS, Mansour S,
Jeffery S. Mutations in KIF11 cause autosomal-dominant microcephaly variably
associated with congenital lymphedema and chorioretinopathy. Am J Hum Genet. 2012 Feb 10;90(2):356-62.

– Ostergaard P, Simpson MA, Connell FC, Steward CG, Brice G, Woollard WJ, Dafou
D, Kilo T, Smithson S, Lunt P, Murday VA, Hodgson S, Keenan R, Pilz DT,
Martinez-Corral I, Makinen T, Mortimer PS, Jeffery S, Trembath RC, Mansour S.
Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat Genet. 2011 Sep 4;43(10):929-31.

– Ostergaard P, Simpson MA, Brice G, Mansour S, Connell FC, Onoufriadis A, Child AH, Hwang J, Kalidas K, Mortimer PS, Trembath R, Jeffery S. Rapid identification of mutations in GJC2 in primary lymphoedema using whole exome sequencing combined with linkage analysis with delineation of the phenotype. J Med Genet. 2011 Feb 28. .

– Mansour S, Connell F, Steward C, Ostergaard P, Brice G, Smithson S, Lunt P, Jeffery S, Dokal I, Vulliamy T, et al.Gibson B, Hodgson S, Cottrell S, Kiely L, Tinworth L, Kalidas K, Mufti G, Cornish J, Keenan R, Mortimer P, Murday V. Emberger syndrome-primary lymphedema with myelodysplasia: report of seven new cases. Am J Med Genet A 152A(9):2287-2296 Sep 2010

– Connell F, Kalidas K, Ostergaard P, Brice G, Homfray T, Roberts L, Bunyan DJ, Mitton S, Mansour S, Mortimer P, Jeffery S; Lymphoedema Consortium. Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia. Hum Genet. 2010 Feb;127(2):231-41.

– Connell F, Homfray T, Thilaganathan B, Bhide A, Jeffrey I, Hutt R, Mortimer P, Mansour S. Congenital vascular malformations: a series of five prenatally diagnosed cases. Am J Med Genet A. 2008 Oct 15;146A(20):2673-80

– Santo S, Mansour S, Thilaganathan B, Homfray T, Papageorghiou A, Calvert S, Bhide A. Prenatal diagnosis of non-immune hydrops fetalis: what do we tell the parents? Prenat Diagn. 2011 Feb;31(2):186-95.

– Devoogdt N, De Groef A, Hendrickx A, Damstra RJ, Christiaansen A, Geraerts I, Vergote I, Van Kampen M. Lymphoedema Functioning, Disability and Health Questionnaire for lower limb lymphoedema (Lymph-ICF-LL): reliability and validity. Physio Ther.(PTJ) 2014:94(5):705-21

– Viehoff PB, Gielink PDC, Damstra RJ, Heerkens YF, van Ravensberg CD, Neumann HAM. Functioning in lymphedema from the patient perspective using the International Classification of Functioning, Disability and Health (ICF) as a reference. Acta Oncologica 2015;54(3):411-21

– Bellini C, Hennekam RC. Clinical disorders of primary malfunctioning of the lymphatic system. Adv Anat Embryol Cell Biol 2014;214:187-204.

– Alders M, Al-Gazali L, Cordeiro I, Dallapiccola B, Garavelli L, Tuysuz B, Salehi F, Haagmans MA, Mook OR, Majoie CB, Mannens MM, Hennekam RC.
Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. Hum Genet 2014;35:1161-1167.

– Bellini C, Donarini G, Paladini D, Calevo MG, Bellini T, Ramenghi LA, Hennekam RC.
Etiology of non-immune hydrops fetalis: An update. Am J Med Genet 2015;167:1082-1088.

– De Wijn RS, Oduber CE, Breugem CC, Alders M, Hennekam RC, van der Horst CM.
Phenotypic variability in a family with capillary malformations caused by a mutation in the RASA1 gene. Eur J Med Genet 2012;55:191-195.

– Hopman SM, Van Rijn RR, Eng C, Bras J, Alders M, van der Horst CM, Hennekam RC, Merks JH. PTEN hamartoma tumor syndrome and Gorham-Stout phenomenon.  Am J Med Genet 2012;158A:1719-1723.

– Alders M, Mendola A, Adès L, Al Gazali L, Bellini C, Dallapiccola B, Edery P, Frank U, Hornshuh F, Huisman SA, Jagadeesh S, Kayserili H, Keng WT, Lev D, Prada CE, Sampson JR, Schmidtke J, Shashi V, van Bever Y, Van der Aa N, Verhagen JM, Verheij JB, Vikkula M, Hennekam RC. Evaluation of Clinical Manifestations in Patients with Severe Lymphedema with and without CCBE1 Mutations. Mol Syndromol 2013;4:107-113.

– Kiefer J, Koulaxouzidis G, Stark GB, Foeldi E, Torio-Padron N, Penna V. An Integrative Therapeutic Concept for Surgical Treatment of Severe Cases of Lymphedema of the Lower Extremity. Obes Surg. 2015 Nov 26. [Epub ahead of print]

– Torio-Padron N, Stark GB, Földi E, Simunovic F. Treatment of male genital lymphedema: an integrated concept. J Plast Reconstr Aesthet Surg. 2015 Feb;68(2):262-8.

– Földi E. [Therapy of lymphedema]. Hautarzt. 2012 Aug;63(8):627-33. doi: 10.1007/s00105-012-2364-5. German.

– Koulaxouzidis G, Goerke SM, Eisenhardt SU, Lampert F, Stark GB, Foeldi E, Torio-Padron N. An integrated therapy concept for reduction of postoperative complications after resection of a panniculus morbidus. Obes Surg. 2012 Apr;22(4):549-54. doi: 10.1007/s11695-011-0561-4.

– Lohrmann C, Foeldi E, Langer M. Lymphocutaneous fistulas: pre-therapeutic evaluation by magnetic resonance lymphangiography. Br J Radiol. 2011 Aug;84(1004):714-8. doi: 10.1259/bjr/14411627. Epub 2010 Dec 15.

– Mortimer PS, Rockson SG. New developments in clinical aspects of lymphatic disease. J Clin Invest. 2014 Mar 3;124(3):915–21.
– International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. 2013. pp. 1–11.
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