MCID: PRM327
MIFTS: 38

Primary Lymphedema

Categories: Blood diseases, Cancer diseases, Cardiovascular diseases, Fetal diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases

Aliases & Classifications for Primary Lymphedema

MalaCards integrated aliases for Primary Lymphedema:

Name: Primary Lymphedema 58
Lymphedema Primary 54

Characteristics:

Orphanet epidemiological data:

58
primary lymphedema
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-5/10000 (Europe); Age of onset: All ages; Age of death: any age;

Classifications:

Orphanet: 58  
Rare circulatory system diseases
Rare skin diseases
Developmental anomalies during embryogenesis


External Ids:

ICD10 via Orphanet 33 I89.0
Orphanet 58 ORPHA77240

Summaries for Primary Lymphedema

MalaCards based summary : Primary Lymphedema, also known as lymphedema primary, is related to lymphatic malformation 1 and hereditary lymphedema ii. An important gene associated with Primary Lymphedema is FLT4 (Fms Related Receptor Tyrosine Kinase 4), and among its related pathways/superpathways are Activation of cAMP-Dependent PKA and TGF-Beta Pathway. The drugs Propranolol and Neurotransmitter Agents have been mentioned in the context of this disorder. Affiliated tissues include skin, lymph node and myeloid, and related phenotypes are Decreased focal adhesion (FA) area, decreased FA length, decreased FA mean intensity, increased number of small and round FAs, increased FA abundance and cardiovascular system

Related Diseases for Primary Lymphedema

Diseases in the Lymphedema family:

Hereditary Lymphedema Hereditary Lymphedema Ic
Hereditary Lymphedema Id Hereditary Lymphedema Ia
Hereditary Lymphedema Ib Hereditary Lymphedema I
Hereditary Lymphedema Ii Congenital Lymphedema
Primary Lymphedema Celsr1-Related Late-Onset Primary Lymphedema
Gjc2-Related Late-Onset Primary Lymphedema

Diseases related to Primary Lymphedema via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 115)
# Related Disease Score Top Affiliating Genes
1 lymphatic malformation 1 32.6 VEGFC GJC2 FLT4
2 hereditary lymphedema ii 30.8 GJC2 FOXC2 FLT4
3 lymphedema 30.6 VEGFC FOXC2 FLT4
4 lymphangioma 29.9 VEGFC FLT4
5 hereditary lymphedema 29.6 VEGFC FOXC2 FLT4
6 klippel-trenaunay-weber syndrome 29.3 FOXC2 FLT4
7 congenital lymphedema 29.2 VEGFD VEGFC FOXC2 FLT4
8 varicose veins 28.9 FOXC2 EPHB4
9 lymphatic system disease 28.9 VEGFC FOXC2 FLT4
10 hennekam syndrome 28.2 VEGFC GJC2 FOXC2 FLT4
11 congenital primary lymphedema of gordon 12.3
12 congenital primary lymphedema without systemic or visceral involvement 12.2
13 late-onset primary lymphedema without systemic or visceral involvement 12.2
14 genetic primary lymphedema 12.2
15 obsolete: primary lymphedema with associated anomalies 12.2
16 primary lymphedema without systemic or visceral involvement 12.2
17 celsr1-related late-onset primary lymphedema 12.2
18 disorder with multisystemic involvement and primary lymphedema 12.2
19 primary lymphedema with systemic or visceral involvement 12.2
20 gjc2-related late-onset primary lymphedema 12.2
21 lymphatic malformation 5 11.6
22 lymphatic malformation 3 11.6
23 warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome 11.5
24 yellow nail syndrome 11.5
25 lymphatic malformation 2 11.5
26 lymphatic malformation 4 11.5
27 hereditary lymphedema i 11.2
28 lymphatic malformation 6 11.2
29 lymphatic malformation 7 11.2
30 cellulitis 10.3
31 hydrops, lactic acidosis, and sideroblastic anemia 10.2
32 lymphedema-distichiasis syndrome 10.1
33 lymphangiosarcoma 10.1
34 distichiasis 10.1
35 gorham's disease 10.1 VEGFC FLT4
36 hydrops fetalis, nonimmune 10.0 FLT4 EPHB4
37 lymphedema, primary, with myelodysplasia 10.0
38 angiosarcoma 10.0
39 erysipelas 10.0
40 lymphangiectasis 10.0
41 kuhnt-junius degeneration 10.0 VEGFD VEGFC
42 hereditary lymphedema ia 10.0 GJC2 FLT4
43 twin-to-twin transfusion syndrome 10.0 VEGFD VEGFC
44 neovascular glaucoma 10.0 VEGFD VEGFC
45 hereditary lymphedema ic 9.9 GJC2 FLT4
46 leukemia, acute myeloid 9.9
47 ptosis 9.9
48 nephrotic syndrome 9.9
49 elephantiasis 9.9
50 cleft lip 9.9

Graphical network of the top 20 diseases related to Primary Lymphedema:



Diseases related to Primary Lymphedema

Symptoms & Phenotypes for Primary Lymphedema

GenomeRNAi Phenotypes related to Primary Lymphedema according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased focal adhesion (FA) area, decreased FA length, decreased FA mean intensity, increased number of small and round FAs, increased FA abundance GR00210-A 8.8 EPHB4 VEGFC VEGFD

MGI Mouse Phenotypes related to Primary Lymphedema:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.55 EPHB4 FLT4 FOXC2 VEGFC VEGFD
2 immune system MP:0005387 9.43 EPHB4 FLT4 FOXC2 GJC2 VEGFC VEGFD
3 mortality/aging MP:0010768 9.1 EPHB4 FLT4 FOXC2 GJC2 VEGFC VEGFD

Drugs & Therapeutics for Primary Lymphedema

Drugs for Primary Lymphedema (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 14)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Propranolol Approved, Investigational Phase 2 525-66-6 4946
2 Neurotransmitter Agents Phase 2
3 Antihypertensive Agents Phase 2
4 Anti-Arrhythmia Agents Phase 2
5 Adrenergic beta-Antagonists Phase 2
6 Adrenergic Antagonists Phase 2
7 Vasodilator Agents Phase 2
8 Adrenergic Agents Phase 2
9 insulin
10 Insulin, Globin Zinc
11 Hypoglycemic Agents
12 Anesthetics
13 Complement System Proteins
14 Vitamins

Interventional clinical trials:

(show all 17)
# Name Status NCT ID Phase Drugs
1 A Prospective Randomized Single Blind Phase III Trial Comparing Flexitouch Home Maintenance Therapy to Standard Home Maintenance Therapy for Lower Extremity Lymphedema Resulting From Treatment of Gynecologic Malignancy Terminated NCT00577317 Phase 3
2 Assessment of Lymphatic Structure and Function Pre- and Post- Treatment and During Recovery in Head and Neck Cancer Patients Using NIR Fluorescence Lymphatic Imaging Completed NCT02946021 Phase 1, Phase 2 NIRFLI with ICG
3 An Intra-patient Dose Escalation Study of Propranolol in Patients With Lymphedema Recruiting NCT02595996 Phase 2 Propranolol
4 Reducing Extremity Lymphedema Through Axillary Lymphatic Preservation Surgery Terminated NCT00932035 Phase 1, Phase 2 isosulfan blue based lymphatic mapping
5 Validation of Metrological Properties of Questionnaire of Quality of Life LYMPHOQOL Unknown status NCT01922635
6 The LymphEdema and Gynecologic Cancer (LEG) Study: Incidence, Risk Factors, and Impact in Newly Diagnosed Patients Unknown status NCT00956670
7 Out-of Pocket Payments in Patients With Primary Lymphedema in France and Inequities of Access to Healthcare Completed NCT02988479
8 Out-of Pocket Payments in Patients With Lymphedema in France and Inequities of Access ti Healthcare Completed NCT02988505
9 Breast Cancer Lymphedema: Role of Insulin Resistance/FOXC2 Completed NCT00383604
10 Physical Therapies in the Decongestive Treatment of Lymphedema: A Multicenter, Randomized, Controlled Study. Completed NCT01748604
11 Assessment of Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced Pneumatic Compression Device at Home Recruiting NCT02661646
12 Histologic Analysis of the Lymphatic Collecting Vessels Used for Minimally Invasive Supermicrosurgical Lymphatico-venous Anastomoses in the Treatment of Lymphedema Recruiting NCT03465930
13 Low-Level Laser in Treatment of Head and Neck Lymphedema: A Pilot Study Recruiting NCT03738332
14 Assessment of Tissue and Biomolecular Complements of Lower Limb Chronic Oedema Recruiting NCT02914808
15 Ketogenic Diet: a Novel Metabolic Strategy to Treat Lymphedema Patients? Recruiting NCT03991897
16 A Pilot Study to Evaluate the Feasibility and Potential Effectiveness of the Flexitouch System Head and Neck Treatment Active, not recruiting NCT03332160
17 An Observational Registry Evaluating the Flexitouch® Plus in Vascular Clinic Patients With Lower Extremity Lymphedema Not yet recruiting NCT04116099

Search NIH Clinical Center for Primary Lymphedema

Genetic Tests for Primary Lymphedema

Anatomical Context for Primary Lymphedema

MalaCards organs/tissues related to Primary Lymphedema:

40
Skin, Lymph Node, Myeloid, Breast, Endothelial, B Cells, Testes

Publications for Primary Lymphedema

Articles related to Primary Lymphedema:

(show top 50) (show all 364)
# Title Authors PMID Year
1
Novel missense mutations in the FOXC2 gene alter transcriptional activity. 54 61
19760751 2009
2
Lymphedema-distichiasis syndrome: a distinct type of primary lymphedema caused by mutations in the FOXC2 gene. 54 61
18986489 2008
3
HGF and MET mutations in primary and secondary lymphedema. 54 61
18564920 2008
4
Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. 54 61
17372167 2007
5
Serum level of VEGF-D in patients with primary lymphedema. 54 61
15693535 2004
6
A novel 5q35.3 subtelomeric deletion syndrome. 54 61
12900893 2003
7
Surgical treatment of Milroy disease. 61
31165487 2020
8
Intra-abdominal chylovenous bypass treats retroperitoneal lymphangiomatosis. 61
31273800 2020
9
The clinical characteristics of lower extremity lymphedema in 440 patients. 61
31992537 2020
10
Clinical and Scintigraphic Predictors of Primary Lower Limb Lymphedema-Volume Reduction During Complete Decongestive Physical Therapy. 61
31944248 2020
11
Volumetric analysis of Non-contrast Magnetic Resonance Lymphangiography in patients affected by lower extremities primary lymphedema. 61
31848805 2019
12
Adult-Onset Primary Lymphedema: A Clinical-Lymphoscintigraphic Study of 26 Patients. 61
30916606 2019
13
Lymphoscintigraphic Abnormalities Associated with Milroy Disease and Lymphedema-Distichiasis Syndrome. 61
31721633 2019
14
Pharmacotherapy Agents in Lymphedema Treatment: A Systematic Review. 61
31815082 2019
15
Functional classification of secondary lymphedema. 61
31737264 2019
16
Characteristics and outcomes of lymphaticovenular anastomosis in older patients with bilateral involvement versus younger patients with unilateral involvement in lower extremity lymphedema. 61
31843479 2019
17
Effects of mobilized peripheral blood stem cells on treatment of primary lower extremity lymphedema. 61
31859244 2019
18
Preliminary Report: The Relevance of Tumor Necrosis Factor-α in Acquired Primary Lymphedema-A Histopathological Investigation. 61
31750769 2019
19
Pregnancy and feto-neonatal outcome in primary lymphedema affected woman. 61
31287250 2019
20
Indocyanine Green Lymphography, Lymphoscintigraphy, and Genetic Analysis in Nonsyndromic Primary Lymphedema: The Distal Dermal Backflow Grading System and the Print Sign. 61
31652480 2019
21
Resource Overutilization in the Diagnosis of Lymphedema Praecox. 61
31706604 2019
22
Lipoaspiration for the Treatment of Lower Limb Lymphedema: A Comprehensive Systematic Review. 61
31754590 2019
23
Comparisons in long-term clinical outcomes among patients with upper or lower extremity lymphedema treated with diverse vascularized lymph node transfer. 61
31489971 2019
24
Genetics of lipedema: new perspectives on genetic research and molecular diagnoses. 61
31298310 2019
25
Indocyanine green lymphography findings in older patients with lower limb lymphedema. 61
31231056 2019
26
LIMPRINT in Specialist Lymphedema Services in United Kingdom, France, Italy, and Turkey. 61
30995195 2019
27
Lymphedema Impact and Prevalence International Study: The Canadian Data. 61
30995190 2019
28
Lymphoscintigraphic Evaluation of Systemic Tracer Uptake in Patients With Primary Lymphedema. 61
30730319 2019
29
Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem. 61
30871556 2019
30
Primary Lymphedema of the Upper Extremities: Clinical and Lymphoscintigraphic Features in 23 Patients. 61
30280960 2019
31
Giant and Extensive Localized Xanthoma Associated with Primary Lymphedema. 61
30745639 2019
32
Skin Grafting Applications in Urology. 61
31239824 2019
33
Comparison of a novel algorithm quantitatively estimating epifascial fibrosis in three-dimensional computed tomography images to other clinical lymphedema grading methods. 61
31821335 2019
34
Outcomes of Vascularized Lymph Node Transfer and Lymphovenous Anastomosis for Treatment of Primary Lymphedema. 61
30656125 2018
35
Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis. 61
30244526 2018
36
Angiosarcoma arising from congenital primary lymphedema. 61
30216524 2018
37
Probing the effect of morphology on lymphatic valve dynamic function. 61
29804152 2018
38
Extraosseous Ewing sarcoma arising in a chronically lymphedematous limb. 61
30148241 2018
39
Unilateral Primary Congenital Lymphedema of the Upper Limb in an 11-Month-Old Infant: A Clinical and Pharmacological Perspective. 61
30337988 2018
40
A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon. 61
30071673 2018
41
Site Specific Evaluation of Lymphatic Vessel Sclerosis in Lower Limb Lymphedema Patients. 61
29338554 2018
42
Primary lymphedema and other lymphatic anomalies are associated with 22q11.2 deletion syndrome. 61
29447908 2018
43
Primary Congenital Lymphedema. 61
29762243 2018
44
Splice-site mutations in VEGFC cause loss of function and Nonne-Milroy-like primary lymphedema. 61
29542815 2018
45
Incidence of Cellulitis among Children with Primary Lymphedema. 61
29791815 2018
46
Use of lymphoscintigraphy to differentiate primary versus secondary lower extremity lymphedema after surgical lymphadenectomy: a retrospective analysis. 61
29631609 2018
47
Lymphatic Drainage of Legs Reduces Edema of the Arms in Children with Lymphedema. 61
29527377 2018
48
[Lymphedema complicated with verrucous papillomatosis]. 61
31448007 2018
49
Modified enteromesenteric bridging operation for primary lymphedema. 61
30337509 2018
50
Mobilization of Fluids in the Intensive Treatment of Primary and Secondary Lymphedemas. 61
29861666 2018

Variations for Primary Lymphedema

Expression for Primary Lymphedema

Search GEO for disease gene expression data for Primary Lymphedema.

Pathways for Primary Lymphedema

Pathways related to Primary Lymphedema according to GeneCards Suite gene sharing:

(show all 25)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.17 VEGFD VEGFC FLT4 EPHB4
2
Show member pathways
13.16 VEGFD VEGFC FLT4 EPHB4
3
Show member pathways
13.02 VEGFD VEGFC FLT4 EPHB4
4
Show member pathways
12.91 VEGFD VEGFC FLT4 EPHB4
5
Show member pathways
12.85 VEGFD VEGFC FLT4 EPHB4
6
Show member pathways
12.55 VEGFD VEGFC FLT4 EPHB4
7
Show member pathways
12.54 VEGFD VEGFC FLT4
8 12.48 VEGFD VEGFC FLT4
9 12.4 VEGFD VEGFC FLT4
10
Show member pathways
12.37 VEGFD VEGFC FLT4
11
Show member pathways
12.33 VEGFD VEGFC FLT4
12
Show member pathways
11.98 VEGFD VEGFC FLT4
13
Show member pathways
11.96 VEGFD VEGFC FLT4
14
Show member pathways
11.84 VEGFD VEGFC FLT4
15
Show member pathways
11.75 VEGFD VEGFC FLT4 EPHB4
16 11.67 VEGFC FLT4 EPHB4
17 11.66 VEGFD VEGFC
18 11.61 VEGFD VEGFC
19
Show member pathways
11.56 VEGFC FLT4
20 11.53 VEGFC FLT4
21 11.24 VEGFD VEGFC
22 11.14 VEGFC FOXC2
23 10.49 VEGFD VEGFC FLT4
24 10.46 VEGFD VEGFC FLT4 EPHB4
25
Show member pathways
10 VEGFD VEGFC FLT4

GO Terms for Primary Lymphedema

Cellular components related to Primary Lymphedema according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 platelet alpha granule lumen GO:0031093 8.62 VEGFD VEGFC

Biological processes related to Primary Lymphedema according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.81 VEGFD VEGFC FOXC2 EPHB4
2 positive regulation of cell proliferation GO:0008284 9.73 VEGFD VEGFC FLT4
3 positive regulation of protein phosphorylation GO:0001934 9.65 VEGFD VEGFC FLT4
4 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007169 9.57 FLT4 EPHB4
5 angiogenesis GO:0001525 9.56 VEGFD VEGFC FLT4 EPHB4
6 positive regulation of endothelial cell migration GO:0010595 9.55 FOXC2 FLT4
7 heart morphogenesis GO:0003007 9.54 FOXC2 EPHB4
8 positive chemotaxis GO:0050918 9.52 VEGFD VEGFC
9 positive regulation of endothelial cell proliferation GO:0001938 9.5 VEGFD VEGFC FLT4
10 positive regulation of cell division GO:0051781 9.49 VEGFD VEGFC
11 induction of positive chemotaxis GO:0050930 9.46 VEGFD VEGFC
12 lymphangiogenesis GO:0001946 9.43 FOXC2 FLT4
13 lymph vessel development GO:0001945 9.4 FOXC2 FLT4
14 positive regulation of mast cell chemotaxis GO:0060754 9.37 VEGFD VEGFC
15 sprouting angiogenesis GO:0002040 9.33 VEGFD VEGFC FLT4
16 vascular endothelial growth factor signaling pathway GO:0038084 9.13 VEGFD VEGFC FLT4
17 vascular endothelial growth factor receptor signaling pathway GO:0048010 8.92 VEGFD VEGFC FOXC2 FLT4

Molecular functions related to Primary Lymphedema according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.26 FLT4 EPHB4
2 chemoattractant activity GO:0042056 9.16 VEGFD VEGFC
3 vascular endothelial growth factor receptor binding GO:0005172 8.96 VEGFD VEGFC
4 vascular endothelial growth factor receptor 3 binding GO:0043185 8.62 VEGFD VEGFC

Sources for Primary Lymphedema

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....