MCID: PRM327
MIFTS: 38

Primary Lymphedema

Categories: 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 i. 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 Adrenergic beta-Antagonists have been mentioned in the context of this disorder. Affiliated tissues include lymph node, skin and endothelial, and related phenotypes are cardiovascular system and immune system

Related Diseases for Primary Lymphedema

Diseases in the Primary Lymphedema family:

Hereditary Lymphedema Hereditary Lymphedema Ic
Hereditary Lymphedema Id Hereditary Lymphedema Ia
Hereditary Lymphedema Ib Hereditary Lymphedema I
Hereditary Lymphedema Ii Congenital 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 111)
# Related Disease Score Top Affiliating Genes
1 lymphatic malformation 1 32.6 VEGFC GJC2 FLT4
2 hereditary lymphedema i 31.8 VEGFC FOXC2 FLT4
3 hereditary lymphedema ii 30.8 GJC2 FOXC2 FLT4
4 lymphangiosarcoma 30.3 VEGFC FLT4
5 lymphangioma 29.8 VEGFC FLT4
6 hereditary lymphedema 29.6 VEGFC FOXC2 FLT4
7 klippel-trenaunay-weber syndrome 29.3 FOXC2 FLT4
8 lymphangitis 29.2 VEGFD VEGFC FLT4
9 congenital lymphedema 29.2 VEGFD VEGFC FOXC2 FLT4
10 lymphedema-distichiasis syndrome 28.7 VEGFC GJC2 FOXC2 FLT4
11 hennekam syndrome 27.6 VEGFC GJC2 FOXC2 FLT4 EPHB4
12 congenital primary lymphedema of gordon 12.3
13 congenital primary lymphedema without systemic or visceral involvement 12.2
14 late-onset primary lymphedema without systemic or visceral involvement 12.2
15 primary lymphedema without systemic or visceral involvement 12.2
16 celsr1-related late-onset primary lymphedema 12.2
17 disorder with multisystemic involvement and primary lymphedema 12.2
18 primary lymphedema with systemic or visceral involvement 12.2
19 gjc2-related late-onset primary lymphedema 12.2
20 lymphatic malformation 5 11.6
21 lymphatic malformation 3 11.6
22 warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome 11.6
23 yellow nail syndrome 11.5
24 lymphatic malformation 2 11.5
25 lymphatic malformation 4 11.5
26 lymphatic malformation 6 11.2
27 lymphatic malformation 7 11.2
28 lymphatic malformation 8 11.2
29 cellulitis 10.3
30 distichiasis 10.1
31 gorham's disease 10.1 VEGFC FLT4
32 skin angiosarcoma 10.0 FLT4 EPHB4
33 lymphedema, primary, with myelodysplasia 10.0
34 angiosarcoma 10.0
35 erysipelas 10.0
36 lymphangiectasis 10.0
37 hydrops fetalis, nonimmune 10.0 FLT4 EPHB4
38 corneal neovascularization 10.0 VEGFC FLT4
39 twin-to-twin transfusion syndrome 10.0 VEGFD VEGFC
40 kuhnt-junius degeneration 9.9 VEGFD VEGFC
41 leukemia, acute myeloid 9.9
42 ptosis 9.9
43 nephrotic syndrome 9.9
44 elephantiasis 9.9
45 myeloid leukemia 9.9
46 cleft lip 9.9
47 cleft lip/palate 9.9
48 rare lymphatic malformation 9.9
49 overgrowth syndrome 9.9
50 breast carcinoma in situ 9.9 VEGFC FLT4

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



Diseases related to Primary Lymphedema

Symptoms & Phenotypes for Primary Lymphedema

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 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Propranolol Approved, Investigational Phase 2 525-66-6 4946
2 Adrenergic beta-Antagonists Phase 2
3 Antihypertensive Agents Phase 2
4 Adrenergic Agents Phase 2
5 Adrenergic Antagonists Phase 2
6 Vasodilator Agents Phase 2
7 Anti-Arrhythmia Agents Phase 2
8 Neurotransmitter Agents Phase 2
9 Insulin, Globin Zinc
10 insulin
11 Anesthetics
12 Complement System Proteins
13 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 A Pilot Study to Evaluate the Feasibility and Potential Effectiveness of the Flexitouch System Head and Neck Treatment Completed NCT03332160
9 Out-of Pocket Payments in Patients With Lymphedema in France and Inequities of Access ti Healthcare Completed NCT02988505
10 Breast Cancer Lymphedema: Role of Insulin Resistance/FOXC2 Completed NCT00383604
11 Physical Therapies in the Decongestive Treatment of Lymphedema: A Multicenter, Randomized, Controlled Study. Completed NCT01748604
12 Assessment of Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced Pneumatic Compression Device at Home Recruiting NCT02661646
13 Histologic Analysis of the Lymphatic Collecting Vessels Used for Minimally Invasive Supermicrosurgical Lymphatico-venous Anastomoses in the Treatment of Lymphedema Recruiting NCT03465930
14 Low-Level Laser in Treatment of Head and Neck Lymphedema: A Pilot Study Recruiting NCT03738332
15 An Observational Registry Evaluating the Flexitouch® Plus in Vascular Clinic Patients With Lower Extremity Lymphedema Recruiting NCT04116099
16 Assessment of Tissue and Biomolecular Complements of Lower Limb Chronic Oedema Recruiting NCT02914808
17 Ketogenic Diet: a Novel Metabolic Strategy to Treat Lymphedema Patients? Recruiting NCT03991897

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
Lymph Node, Skin, Endothelial, Breast, Testes, Lung, Myeloid

Publications for Primary Lymphedema

Articles related to Primary Lymphedema:

(show top 50) (show all 373)
# Title Authors PMID Year
1
Novel missense mutations in the FOXC2 gene alter transcriptional activity. 61 54
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. 61 54
18564920 2008
4
Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. 61 54
17372167 2007
5
Serum level of VEGF-D in patients with primary lymphedema. 61 54
15693535 2004
6
A novel 5q35.3 subtelomeric deletion syndrome. 61 54
12900893 2003
7
Characteristics and outcomes of lymphaticovenular anastomosis in older patients with bilateral involvement versus younger patients with unilateral involvement in lower extremity lymphedema. 61
31843479 2020
8
Multilymphosome injection indocyanine green lymphography can detect more lymphatic vessels than lymphoscintigraphy in lymphedematous limbs. 61
32115379 2020
9
Preliminary Report: The Relevance of Tumor Necrosis Factor-α in Acquired Primary Lymphedema-A Histopathological Investigation. 61
31750769 2020
10
Analysis of Collateral Lymphatic Circulation in Patients with Lower Limb Lymphedema Using Magnetic Resonance Lymphangiography. 61
32470617 2020
11
The utility of surgical and conservative combination therapy for advanced stage lymphedema. 61
32470619 2020
12
Microsurgery for management of primary and secondary lymphedema: First experience in Israel. 61
32446874 2020
13
Clinical and Scintigraphic Predictors of Primary Lower Limb Lymphedema-Volume Reduction During Complete Decongestive Physical Therapy. 61
31944248 2020
14
A systematic review of magnetic resonance lymphography for the evaluation of peripheral lymphedema. 61
32417145 2020
15
Effects of mobilized peripheral blood stem cells on treatment of primary lower extremity lymphedema. 61
31859244 2020
16
A Case of Congenital Lymphedema Complicated by Chronic Chylous Effusions and Recurrent Pericardial Effusion Requiring Pericardial Window. 61
32550076 2020
17
Volumetric analysis of Non-contrast Magnetic Resonance Lymphangiography in patients affected by lower extremities primary lymphedema. 61
31848805 2020
18
Assessment of primary lymphedema and post-thrombotic lower limb edema patient's pathway. 61
32265015 2020
19
Indocyanine green lymphography findings in older patients with lower limb lymphedema. 61
31231056 2020
20
Surgical Management of Lymphedema. 61
32308240 2020
21
Indocyanine Green Lymphography, Lymphoscintigraphy, and Genetic Analysis in Nonsyndromic Primary Lymphedema: The Distal Dermal Backflow Grading System and the Print Sign. 61
31652480 2020
22
Comparisons in long-term clinical outcomes among patients with upper or lower extremity lymphedema treated with diverse vascularized lymph node transfer. 61
31489971 2020
23
Evaluation and selection of lower limb lymphedema patients for lymphaticovenular anastomosis: A prospective study. 61
32209243 2020
24
The clinical characteristics of lower extremity lymphedema in 440 patients. 61
31992537 2020
25
Surgical treatment of Milroy disease. 61
31165487 2020
26
Intra-abdominal chylovenous bypass treats retroperitoneal lymphangiomatosis. 61
31273800 2020
27
Lymphoscintigraphic Abnormalities Associated with Milroy Disease and Lymphedema-Distichiasis Syndrome. 61
31721633 2019
28
Functional classification of secondary lymphedema. 61
31737264 2019
29
Adult-Onset Primary Lymphedema: A Clinical-Lymphoscintigraphic Study of 26 Patients. 61
30916606 2019
30
Pharmacotherapy Agents in Lymphedema Treatment: A Systematic Review. 61
31815082 2019
31
Pregnancy and feto-neonatal outcome in primary lymphedema affected woman. 61
31287250 2019
32
Resource Overutilization in the Diagnosis of Lymphedema Praecox. 61
31706604 2019
33
Lipoaspiration for the Treatment of Lower Limb Lymphedema: A Comprehensive Systematic Review. 61
31754590 2019
34
Genetics of lipedema: new perspectives on genetic research and molecular diagnoses. 61
31298310 2019
35
Lymphoscintigraphic Evaluation of Systemic Tracer Uptake in Patients With Primary Lymphedema. 61
30730319 2019
36
LIMPRINT in Specialist Lymphedema Services in United Kingdom, France, Italy, and Turkey. 61
30995195 2019
37
Lymphedema Impact and Prevalence International Study: The Canadian Data. 61
30995190 2019
38
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
39
Primary Lymphedema of the Upper Extremities: Clinical and Lymphoscintigraphic Features in 23 Patients. 61
30280960 2019
40
Giant and Extensive Localized Xanthoma Associated with Primary Lymphedema. 61
30745639 2019
41
Comparison of a novel algorithm quantitatively estimating epifascial fibrosis in three-dimensional computed tomography images to other clinical lymphedema grading methods. 61
31821335 2019
42
Skin Grafting Applications in Urology. 61
31239824 2019
43
Outcomes of Vascularized Lymph Node Transfer and Lymphovenous Anastomosis for Treatment of Primary Lymphedema. 61
30656125 2018
44
Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis. 61
30244526 2018
45
Angiosarcoma arising from congenital primary lymphedema. 61
30216524 2018
46
Probing the effect of morphology on lymphatic valve dynamic function. 61
29804152 2018
47
Unilateral Primary Congenital Lymphedema of the Upper Limb in an 11-Month-Old Infant: A Clinical and Pharmacological Perspective. 61
30337988 2018
48
Extraosseous Ewing sarcoma arising in a chronically lymphedematous limb. 61
30148241 2018
49
A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon. 61
30071673 2018
50
Site Specific Evaluation of Lymphatic Vessel Sclerosis in Lower Limb Lymphedema Patients. 61
29338554 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
13.18 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
12.89 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 11.26 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 9.8 VEGFD VEGFC FOXC2 FLT4 EPHB4
2 positive regulation of cell proliferation GO:0008284 9.74 VEGFD VEGFC FLT4
3 positive regulation of protein phosphorylation GO:0001934 9.67 VEGFD VEGFC FLT4
4 positive regulation of kinase activity GO:0033674 9.56 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 cell division GO:0051781 9.51 VEGFD VEGFC
10 positive regulation of endothelial cell proliferation GO:0001938 9.5 VEGFD VEGFC FLT4
11 induction of positive chemotaxis GO:0050930 9.48 VEGFD VEGFC
12 lymph vessel development GO:0001945 9.46 FOXC2 FLT4
13 lymphangiogenesis GO:0001946 9.43 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
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