MCID: PRM327
MIFTS: 35

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 lymphatic malformation 5. An important gene associated with Primary Lymphedema is FLT4 (Fms Related Receptor Tyrosine Kinase 4), and among its related pathways/superpathways are Focal Adhesion and Pathways in cancer. The drugs Propranolol and Anti-Arrhythmia Agents have been mentioned in the context of this disorder. Affiliated tissues include endothelial, lymph node and myeloid, and related phenotypes are cardiovascular system and homeostasis/metabolism

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 102)
# Related Disease Score Top Affiliating Genes
1 lymphatic malformation 1 32.2 VEGFC FLT4
2 lymphatic malformation 5 31.7 FOXC2 FLT4
3 hereditary lymphedema ii 31.7 FOXC2 FLT4
4 hereditary lymphedema i 31.6 VEGFC FOXC2 FLT4
5 elephantiasis 30.1 VEGFC FLT4
6 hereditary lymphedema 30.0 VEGFC FOXC2 FLT4
7 lymphangioma 30.0 VEGFC FLT4
8 congenital lymphedema 29.8 VEGFD VEGFC FOXC2 FLT4
9 lymphedema-distichiasis syndrome 29.8 VEGFC FOXC2 FLT4
10 klippel-trenaunay-weber syndrome 29.6 FOXC2 FLT4
11 hennekam syndrome 28.9 VEGFC GATA2 FOXC2 FLT4
12 congenital primary lymphedema of gordon 11.2
13 lymphatic malformation 3 11.1
14 warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome 11.1
15 congenital primary lymphedema without systemic or visceral involvement 11.0
16 late-onset primary lymphedema without systemic or visceral involvement 11.0
17 primary lymphedema without systemic or visceral involvement 11.0
18 celsr1-related late-onset primary lymphedema 11.0
19 disorder with multisystemic involvement and primary lymphedema 11.0
20 primary lymphedema with systemic or visceral involvement 11.0
21 gjc2-related late-onset primary lymphedema 11.0
22 yellow nail syndrome 11.0
23 lymphatic malformation 2 11.0
24 lymphatic malformation 4 11.0
25 lymphatic malformation 6 11.0
26 lymphatic malformation 7 11.0
27 lymphatic malformation 8 11.0
28 cellulitis 10.3
29 erysipelas 10.1
30 lymphangiosarcoma 10.1
31 distichiasis 10.1
32 lymphedema, primary, with myelodysplasia 10.1
33 hereditary lymphedema ia 10.1
34 lymphangiectasis 10.1
35 gorham's disease 10.1 VEGFC FLT4
36 pyriform sinus cancer 10.0 VEGFC FLT4
37 angiosarcoma 10.0
38 twin-to-twin transfusion syndrome 10.0 VEGFD VEGFC
39 kuhnt-junius degeneration 10.0 VEGFD VEGFC
40 hypotrichosis-lymphedema-telangiectasia syndrome 10.0 FOXC2 FLT4
41 leukemia, acute myeloid 9.9
42 lipedema 9.9
43 immunodeficiency 21 9.9
44 ptosis 9.9
45 nephrotic syndrome 9.9
46 myeloid leukemia 9.9
47 cleft lip 9.9
48 cleft lip/palate 9.9
49 rare lymphatic malformation 9.9
50 overgrowth syndrome 9.9

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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.63 CALCRL FLT4 FOXC2 GATA2 VEGFC VEGFD
2 homeostasis/metabolism MP:0005376 9.43 CALCRL FLT4 FOXC2 GATA2 VEGFC VEGFD
3 mortality/aging MP:0010768 9.1 CALCRL FLT4 FOXC2 GATA2 VEGFC VEGFD

Drugs & Therapeutics for Primary Lymphedema

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

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Propranolol Approved, Investigational Phase 2 525-66-6 4946
2 Anti-Arrhythmia Agents Phase 2
3 Vasodilator Agents Phase 2
4 Adrenergic Antagonists Phase 2
5 Adrenergic beta-Antagonists Phase 2
6 Antihypertensive Agents Phase 2
7 Neurotransmitter Agents Phase 2
8 Adrenergic Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 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
2 An Intra-patient Dose Escalation Study of Propranolol in Patients With Lymphedema Terminated NCT02595996 Phase 2 Propranolol
3 A Pilot Study to Evaluate the Feasibility and Potential Effectiveness of the Flexitouch System Head and Neck Treatment Completed NCT03332160
4 Out-of Pocket Payments in Patients With Lymphedema in France and Inequities of Access ti Healthcare Completed NCT02988505
5 Out-of Pocket Payments in Patients With Primary Lymphedema in France and Inequities of Access to Healthcare Completed NCT02988479
6 Physical Therapies in the Decongestive Treatment of Lymphedema: A Multicenter, Randomized, Controlled Study. Completed NCT01748604

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
Endothelial, Lymph Node, Myeloid

Publications for Primary Lymphedema

Articles related to Primary Lymphedema:

(show top 50) (show all 394)
# 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. 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. 61 54
12900893 2003
7
A Case of Elephantiasis Nostras Verrucosa Secondary to Lymphedema Praecox Complicated by Congestive Cardiac Failure. 61
33714971 2021
8
Dysfunction of dermal initial lymphatics of the arm and upper body quadrant causes congenital arm lymphedema. 61
32599305 2021
9
Hennekam lymphangiectasia syndrome: A rare case of primary lymphedema. 61
33769747 2021
10
Surgical Treatment of Primary Penile Scrotal Lymphedema: A Case Report. 61
32861698 2021
11
Analysis of collateral lymphatic circulation in patients with lower limb lymphedema using magnetic resonance lymphangiography. 61
32470617 2021
12
Chubby Infant - Should One Worry? An Infant with Primary lymphedema - Mini Review and Case Report. 61
32659845 2021
13
The St George's Classification Algorithm of Primary Lymphatic Anomalies. 61
33395557 2021
14
Clinical aspects of congenital primary lymphedema. 61
32986626 2021
15
Development and Physiological Functions of the Lymphatic System - Insights from Genetic Studies of Lymphedema. 61
33507128 2021
16
Sex Hormones in Lymphedema. 61
33573286 2021
17
Primary Lymphedema: Update on Genetic Basis and Management. 61
33502936 2021
18
The utility of surgical and conservative combination therapy for advanced stage lymphedema. 61
32470619 2021
19
Microsurgery for management of primary and secondary lymphedema. 61
32446874 2021
20
Primary lymphedema French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins). 61
33407666 2021
21
Evaluation and selection of lower limb lymphedema patients for lymphaticovenular anastomosis: A prospective study. 61
32209243 2020
22
New Insights into the Pathophysiology of Primary and Secondary Lymphedema: Histopathological Studies on Human Lymphatic Collecting Vessels. 61
32716244 2020
23
Study of a supplement and a genetic test for lymphedema management. 61
33170163 2020
24
A dual role for Tbx1 in cardiac lymphangiogenesis through genetic interaction with Vegfr3. 61
32951265 2020
25
Lymphedema microsurgery improved outcomes of pediatric primary extremity lymphedema. 61
32652644 2020
26
Rest/stress intradermal lymphoscintigraphy in diagnosis of lipedema. 61
33623507 2020
27
A systematic review of magnetic resonance lymphography for the evaluation of peripheral lymphedema. 61
32417145 2020
28
Shaving Technique and Compression Therapy for Elephantiasis Nostras Verrucosa (Lymphostatic Verrucosis) of Forefeet and Toes in End-Stage Primary Lymphedema: A 5 Year Follow-Up Study in 28 Patients and a Review of the Literature. 61
32998425 2020
29
Characterization of ANGPT2 mutations associated with primary lymphedema. 61
32908006 2020
30
The clinical characteristics of lower extremity lymphedema in 440 patients. 61
31992537 2020
31
Is the Effect of Complex Decongestive Therapy the Same for Primary and Secondary Lower Lymphedema? 61
32780623 2020
32
Resource overutilization in the diagnosis of lymphedema praecox. 61
31706604 2020
33
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
34
Preliminary Report: The Relevance of Tumor Necrosis Factor-α in Acquired Primary Lymphedema-A Histopathological Investigation. 61
31750769 2020
35
Multilymphosome injection indocyanine green lymphography can detect more lymphatic vessels than lymphoscintigraphy in lymphedematous limbs. 61
32115379 2020
36
Effects of mobilized peripheral blood stem cells on treatment of primary lower extremity lymphedema. 61
31859244 2020
37
A Case of Congenital Lymphedema Complicated by Chronic Chylous Effusions and Recurrent Pericardial Effusion Requiring Pericardial Window. 61
32550076 2020
38
Clinical and Scintigraphic Predictors of Primary Lower Limb Lymphedema-Volume Reduction During Complete Decongestive Physical Therapy. 61
31944248 2020
39
Assessment of primary lymphedema and post-thrombotic lower limb edema patient's pathway. 61
32265015 2020
40
Volumetric analysis of Non-contrast Magnetic Resonance Lymphangiography in patients affected by lower extremities primary lymphedema. 61
31848805 2020
41
Surgical Management of Lymphedema. 61
32308240 2020
42
Indocyanine green lymphography findings in older patients with lower limb lymphedema. 61
31231056 2020
43
Indocyanine Green Lymphography, Lymphoscintigraphy, and Genetic Analysis in Nonsyndromic Primary Lymphedema: The Distal Dermal Backflow Grading System and the Print Sign. 61
31652480 2020
44
Comparisons in long-term clinical outcomes among patients with upper or lower extremity lymphedema treated with diverse vascularized lymph node transfer. 61
31489971 2020
45
Mutations in the ARAP3 Gene in Three Families with Primary Lymphedema Negative for Mutations in Known Lymphedema-Associated Genes. 61
32908855 2020
46
[The morphology of the connective tissue matrix and lymphatic bed of the external genitalia in primary massive localized lymphedema]. 61
33054035 2020
47
Intra-abdominal chylovenous bypass treats retroperitoneal lymphangiomatosis. 61
31273800 2020
48
Surgical treatment of Milroy disease. 61
31165487 2020
49
Lymphoscintigraphic Abnormalities Associated with Milroy Disease and Lymphedema-Distichiasis Syndrome. 61
31721633 2019
50
Functional classification of secondary lymphedema. 61
31737264 2019

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 19)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.51 VEGFD VEGFC FLT4
2 12.43 VEGFD VEGFC FLT4
3 12.34 VEGFD VEGFC FLT4
4
Show member pathways
12.3 VEGFD VEGFC FLT4
5
Show member pathways
12.25 VEGFD VEGFC FLT4
6
Show member pathways
11.98 VEGFD VEGFC FLT4
7
Show member pathways
11.87 VEGFD VEGFC FLT4
8
Show member pathways
11.81 VEGFD VEGFC FLT4
9
Show member pathways
11.75 VEGFD VEGFC FLT4
10 11.71 VEGFD VEGFC FLT4
11 11.63 VEGFD VEGFC
12 11.58 VEGFD VEGFC
13
Show member pathways
11.52 VEGFC FLT4
14 11.49 VEGFC FLT4
15 11.17 VEGFD VEGFC
16 11.07 VEGFC FOXC2
17 10.63 VEGFD VEGFC FLT4
18 10.49 VEGFD VEGFC FLT4
19
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 19)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.87 VEGFD VEGFC FOXC2 FLT4
2 cell differentiation GO:0030154 9.84 VEGFD VEGFC GATA2 FOXC2
3 positive regulation of cell proliferation GO:0008284 9.71 VEGFD VEGFC FLT4 CALCRL
4 positive regulation of protein phosphorylation GO:0001934 9.69 VEGFD VEGFC FLT4
5 positive regulation of angiogenesis GO:0045766 9.65 VEGFD VEGFC GATA2
6 positive regulation of endothelial cell migration GO:0010595 9.58 FOXC2 FLT4
7 positive regulation of blood vessel endothelial cell migration GO:0043536 9.58 VEGFC GATA2
8 positive regulation of cell division GO:0051781 9.56 VEGFD VEGFC
9 angiogenesis GO:0001525 9.56 VEGFD VEGFC FLT4 CALCRL
10 positive chemotaxis GO:0050918 9.55 VEGFD VEGFC
11 positive regulation of cell migration involved in sprouting angiogenesis GO:0090050 9.52 GATA2 FOXC2
12 positive regulation of endothelial cell proliferation GO:0001938 9.5 VEGFD VEGFC FLT4
13 induction of positive chemotaxis GO:0050930 9.49 VEGFD VEGFC
14 lymphangiogenesis GO:0001946 9.46 FOXC2 FLT4
15 lymph vessel development GO:0001945 9.43 FOXC2 FLT4
16 positive regulation of mast cell chemotaxis GO:0060754 9.37 VEGFD VEGFC
17 sprouting angiogenesis GO:0002040 9.33 VEGFD VEGFC FLT4
18 vascular endothelial growth factor signaling pathway GO:0038084 9.13 VEGFD VEGFC FLT4
19 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 chemoattractant activity GO:0042056 9.16 VEGFD VEGFC
2 vascular endothelial growth factor receptor binding GO:0005172 8.96 VEGFD VEGFC
3 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
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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