MCID: HRD007
MIFTS: 37

Hereditary Lymphedema

Categories: Blood diseases, Cancer diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Neuronal diseases, Oral diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Hereditary Lymphedema

MalaCards integrated aliases for Hereditary Lymphedema:

Name: Hereditary Lymphedema 12 37 15
Nonne-Milroy Lymphedema 12
Milroy's Disease 12
Milroy Disease 73

Classifications:



External Ids:

Disease Ontology 12 DOID:0050580
ICD9CM 35 757.0
SNOMED-CT 68 75127007
KEGG 37 H00535

Summaries for Hereditary Lymphedema

Disease Ontology : 12 A lymphedema commonly located in legs, caused_by congenital abnormalities in the lymphatic system.

MalaCards based summary : Hereditary Lymphedema, also known as nonne-milroy lymphedema, is related to hereditary lymphedema i and lymphedema, hereditary, ii. An important gene associated with Hereditary Lymphedema is FLT4 (Fms Related Tyrosine Kinase 4), and among its related pathways/superpathways are MAPK signaling pathway and Focal adhesion. The drugs Paroxetine and Neurotransmitter Uptake Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include legs and heart, and related phenotypes are cardiovascular system and digestive/alimentary

Wikipedia : 76 Milroy''s disease (MD) is a familial disease characterized by lymphedema, commonly in the legs, caused... more...

Related Diseases for Hereditary Lymphedema

Diseases in the Lymphedema family:

Lymphedema, Hereditary, Ia Lymphedema, Hereditary, Ii
Lymphedema, Congenital Recessive Lymphedema, Hereditary, Ib
Lymphedema, Hereditary, Ic Lymphedema, Hereditary, Id
Lymphedema, Hereditary, Iii Hereditary Lymphedema
Hereditary Lymphedema I Congenital Lymphedema

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

(show all 34)
# Related Disease Score Top Affiliating Genes
1 hereditary lymphedema i 33.0 CHMP1A FLT4 PHF19 SLC25A3 SOX18
2 lymphedema, hereditary, ii 32.8 FOXC1 FOXC2 SOX18
3 lymphedema-distichiasis syndrome 32.3 FOXC2 FOXL1
4 yellow nail syndrome 31.7 FOXC2 SOX18
5 lymphedema 30.5 FLT4 FOXC2 SOX18 VEGFC
6 lymphangiosarcoma 30.0 FLT4 VEGFC
7 distichiasis 29.9 CHMP1A FOXC1 FOXC2 FOXL1
8 lymphedema, hereditary, ia 11.9
9 lymphedema, hereditary, id 11.8
10 lymphedema, hereditary, ic 11.8
11 lymphedema, hereditary, ib 11.7
12 lymphedema, hereditary, iii 11.1
13 chylothorax, congenital 10.1 FLT4 FOXC2
14 syngnathia 10.1 FOXC1 FOXC2
15 gorham's disease 10.0 FLT4 VEGFC
16 congenital hydrocephalus 10.0 FOXC1 FOXL1
17 hennekam syndrome 10.0 FLT4 VEGFC
18 lymphangioma 10.0 FLT4 VEGFC
19 klippel-trenaunay-weber syndrome 10.0 FLT4 FOXC2 SOX18
20 venous malformations, multiple cutaneous and mucosal 10.0 FLT4 FOXC2 SOX18
21 lymphatic system disease 9.9 FLT4 FOXC2 VEGFC
22 breast carcinoma in situ 9.9 FLT4 VEGFC
23 hypoplastic left heart syndrome 9.9 FOXC2 FOXL1
24 cholestasis-lymphedema syndrome 9.8
25 hydrops fetalis, nonimmune, and/or atrial septal defect 9.8
26 diabetes mellitus 9.8
27 cholestasis 9.8
28 obstructive jaundice 9.8
29 elephantiasis 9.8
30 fetal edema 9.8
31 hemangioendothelioma 9.8
32 hydrops fetalis 9.8
33 kaposiform hemangioendothelioma 9.8
34 congenital lymphedema 9.8 FLT4 FOXC2 HNRNPH1 VEGFC

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



Diseases related to Hereditary Lymphedema

Symptoms & Phenotypes for Hereditary Lymphedema

MGI Mouse Phenotypes related to Hereditary Lymphedema:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.5 FLT4 FOXC1 FOXC2 PHF19 SLC25A3 SOX18
2 digestive/alimentary MP:0005381 9.02 FLT4 FOXC1 FOXC2 FOXL1 SOX18

Drugs & Therapeutics for Hereditary Lymphedema

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

(show all 33)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Paroxetine Approved, Investigational Phase 3 61869-08-7 43815
2 Neurotransmitter Uptake Inhibitors Phase 3
3 Psychotropic Drugs Phase 3
4 Antidepressive Agents Phase 3
5 Antidepressive Agents, Second-Generation Phase 3
6 Cytochrome P-450 Enzyme Inhibitors Phase 3
7 Serotonin Uptake Inhibitors Phase 3
8 Serotonin Agents Phase 3
9 Neurotransmitter Agents Phase 3,Phase 2
10 Cytochrome P-450 CYP2D6 Inhibitors Phase 3
11
Serotonin Investigational, Nutraceutical Phase 3 50-67-9 5202
12
Propranolol Approved, Investigational Phase 2 525-66-6 4946
13
Imiquimod Approved, Investigational Phase 2 99011-02-6 57469
14 Vasodilator Agents Phase 2
15 Adrenergic Agents Phase 2
16 Anti-Arrhythmia Agents Phase 2
17 Adrenergic beta-Antagonists Phase 2
18 Antihypertensive Agents Phase 2
19 Adrenergic Antagonists Phase 2
20 interferons Phase 2
21 Adjuvants, Immunologic Phase 2
22 Interferon Inducers Phase 2
23 Immunologic Factors Phase 2
24
Glucosamine Approved, Investigational 3416-24-8 439213
25 Glucuronyl glucosamine glycan sulfate
26 Anticoagulants
27 Lipid Regulating Agents
28 Anesthetics
29 Hypoglycemic Agents
30 Hypolipidemic Agents
31 Fibrinolytic Agents
32 Antimetabolites
33 Complement System Proteins

Interventional clinical trials:

(show all 15)
# Name Status NCT ID Phase Drugs
1 Efficacy/Safety Study of Brisdelle™ (Formerly Known as Mesafem) in the Treatment of Vasomotor Symptoms (VMS) Completed NCT01361308 Phase 3 Brisdelle (paroxetine mesylate);Placebo capsules
2 A Study of Oral VT-1161 for the Treatment of Patients With Recurrent Vaginal Candidiasis (Yeast Infection) Recruiting NCT03561701 Phase 3 VT-1161;Placebo
3 Propranolol Dose Escalation in Lymphedema in Patients Recruiting NCT02595996 Phase 2 Propranolol
4 Evaluation of VGX-3100 and Electroporation Alone or in Combination With Imiquimod for the Treatment of HPV-16 and/or HPV-18 Related Vulvar HSIL (Also Referred as: VIN 2 or VIN 3) Recruiting NCT03180684 Phase 2 Imiquimod 5% cream
5 Out-of Pocket Payments in Patients With Lymphedema Unknown status NCT02988479
6 Out-of Pocket Payments With Lymphedema in France Unknown status NCT02988505
7 Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment Unknown status NCT01273909
8 Validation of Metrological Properties of Lymphoqol Unknown status NCT01922635 Not Applicable
9 Validation of a New Method of Limb Volumetry Unknown status NCT01574911
10 Physical Therapies in the Decongestive Treatment of Lymphedema Completed NCT01748604 Not Applicable
11 Histologic Analysis of the Lymphatic Vessels Used for Supermicrosurgical Lymphatico-venous Anastomoses in Lymphedema Recruiting NCT03465930
12 Oedema Study : Chroedem Recruiting NCT02914808
13 A Pilot Study to Evaluate the Feasibility and Potential Effectiveness of the Flexitouch System Head and Neck Treatment Recruiting NCT03332160 Not Applicable
14 Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced Pneumatic Compression Device (PCD) Recruiting NCT02661646
15 Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders Enrolling by invitation NCT00833599 NIRFLI with ICG

Search NIH Clinical Center for Hereditary Lymphedema

Genetic Tests for Hereditary Lymphedema

Anatomical Context for Hereditary Lymphedema

The Foundational Model of Anatomy Ontology organs/tissues related to Hereditary Lymphedema:

19
Legs

MalaCards organs/tissues related to Hereditary Lymphedema:

41
Heart

Publications for Hereditary Lymphedema

Articles related to Hereditary Lymphedema:

(show all 37)
# Title Authors Year
1
Hereditary Lymphedema of the Leg - A Case Report. ( 28785330 )
2017
2
A novel mutation in CELSR1 is associated with hereditary lymphedema. ( 26855770 )
2016
3
A Novel Missense Mutation in FLT4 Causes Autosomal Recessive Hereditary Lymphedema. ( 26091405 )
2015
4
Antenatal presentation of hereditary lymphedema type I. ( 25896638 )
2015
5
Hereditary Lymphedema, Characteristics, and Variations in 17 Adult Patients with Lymphedema Cholestasis Syndrome 1/Aagenaes Syndrome. ( 25317502 )
2014
6
Excision of Elephantiasis Nostras Verrucosa Lesions in a Patient With Hereditary Lymphedema: Case Report and Review of the Literature. ( 25441846 )
2014
7
Hydrops fetalis and pulmonary lymphangiectasia due to FOXC2 mutation: an autosomal dominant hereditary lymphedema syndrome with variable expression. ( 21918810 )
2012
8
Identification of a novel VEGFR-3 missense mutation in a Chinese family with hereditary lymphedema type I. ( 17945164 )
2007
9
Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations. ( 16965327 )
2006
10
Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3. ( 16924388 )
2006
11
Clinical variability in a Japanese hereditary lymphedema type I family with an FLT4 mutation. ( 15904433 )
2005
12
The establishment of a predictive mutational model of the forkhead domain through the analyses of FOXC2 missense mutations identified in patients with hereditary lymphedema with distichiasis. ( 16081467 )
2005
13
Stewart-Treves syndrome as a rare complication of a hereditary lymphedema. ( 15061047 )
2004
14
A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus. ( 15523639 )
2004
15
Kaposiform hemangioendothelioma associated with Milroy's disease (primary hereditary lymphedema). ( 12861592 )
2003
16
Syndromic classification of hereditary lymphedema. ( 14992570 )
2003
17
Age of onset in hereditary lymphedema. ( 12838201 )
2003
18
Prenatal ultrasonographic diagnosis of atypical Nonne-Milroy lymphedema. ( 12528167 )
2003
19
A model for gene therapy of human hereditary lymphedema. ( 11592985 )
2001
20
Prenatal diagnosis of Nonne-Milroy lymphedema. ( 11547763 )
2001
21
Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. ( 10856194 )
2000
22
Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. ( 11078474 )
2000
23
Hereditary lymphedema: evidence for linkage and genetic heterogeneity. ( 9817924 )
1998
24
Lymphangiosarcoma of the pubic region: a rare complication arising in congenital non-hereditary lymphedema. ( 9854166 )
1998
25
Lymphangiosarcoma in late-onset hereditary lymphedema: case report and nosological implications. ( 7747790 )
1995
26
Hereditary lymphedema and distichiasis. ( 2064580 )
1991
27
Hereditary lymphedema in Hereford cattle. ( 2039787 )
1991
28
Congenital hereditary lymphedema (Nonne/Milroy). ( 2616174 )
1989
29
Scintilymphangiography with 99 mTc-antimony sulfide colloid in hereditary lymphedema (Nonne-Milroy diseases). ( 709985 )
1978
30
Congenital hereditary lymphedema in the pig. ( 642582 )
1978
31
The pathogenesis of congenital hereditary lymphedema in the pig. ( 642583 )
1978
32
Chronic hereditary lymphedema of the legs with congenital conjunctival lymphedema. ( 5020171 )
1972
33
Hereditary lymphedema and obstructive jaundice. ( 5544157 )
1971
34
PLEURAL EFFUSION IN CHRONIC HEREDITARY LYMPHEDEMA (NONNE, MILROY, MEIGE'S DISEASE). REPORT OF TWO CASES. ( 14115303 )
1964
35
Genetic and physiological aspects of a family with chronic hereditary lymphedema (Nonne-Milroy-Meige's disease) and hereditary angioneurotic edema. ( 13533392 )
1958
36
Prednisone in the management of idiopathic hereditary lymphedema (Milroy's disease). ( 13345610 )
1956
37
Chronic hereditary lymphedema (Nonne-Milroy-Meige's Disease). ( 15418956 )
1950

Variations for Hereditary Lymphedema

Cosmic variations for Hereditary Lymphedema:

9
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM52970 GNA11 soft tissue,leg,haemangioma,congenital c.626A>C p.Q209P 19:3118944-3118944 5

Expression for Hereditary Lymphedema

Search GEO for disease gene expression data for Hereditary Lymphedema.

Pathways for Hereditary Lymphedema

Pathways related to Hereditary Lymphedema according to KEGG:

37
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 Focal adhesion hsa04510
3 PI3K-Akt signaling pathway hsa04151
4 Rap1 signaling pathway hsa04015

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

# Super pathways Score Top Affiliating Genes
1 10.52 FLT4 VEGFC
2 10.46 FOXC1 FOXC2 VEGFC
3
Show member pathways
10.16 FLT4 VEGFC

GO Terms for Hereditary Lymphedema

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

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.9 FOXC1 FOXC2 PHF19 SOX18
2 cell differentiation GO:0030154 9.88 FLT4 FOXC1 FOXC2 FOXL1 SOX18 VEGFC
3 heart development GO:0007507 9.78 FOXC1 FOXC2 FOXL1 SOX18
4 angiogenesis GO:0001525 9.76 FLT4 FOXC1 SOX18 VEGFC
5 anatomical structure morphogenesis GO:0009653 9.7 FOXC1 FOXC2 FOXL1
6 somitogenesis GO:0001756 9.64 FOXC1 FOXC2
7 positive regulation of endothelial cell migration GO:0010595 9.63 FLT4 FOXC2
8 heart morphogenesis GO:0003007 9.63 FOXC1 FOXC2
9 collagen fibril organization GO:0030199 9.62 FOXC1 FOXC2
10 ureteric bud development GO:0001657 9.61 FOXC1 FOXC2
11 blood vessel remodeling GO:0001974 9.61 FOXC1 FOXC2
12 blood vessel development GO:0001568 9.61 FOXC1 FOXC2 SOX18
13 sprouting angiogenesis GO:0002040 9.59 FLT4 VEGFC
14 vasculature development GO:0001944 9.58 FLT4 SOX18
15 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.58 FOXC1 FOXC2
16 artery morphogenesis GO:0048844 9.57 FOXC1 FOXC2
17 neural crest cell development GO:0014032 9.56 FOXC1 FOXC2
18 regulation of blood vessel size GO:0050880 9.55 FOXC1 FOXC2
19 cardiac muscle cell proliferation GO:0060038 9.54 FOXC1 FOXC2
20 regulation of organ growth GO:0046620 9.51 FOXC1 FOXC2
21 embryonic heart tube development GO:0035050 9.5 FOXC1 FOXC2 SOX18
22 paraxial mesoderm formation GO:0048341 9.49 FOXC1 FOXC2
23 vascular endothelial growth factor signaling pathway GO:0038084 9.43 FLT4 FOXC1 VEGFC
24 negative regulation of apoptotic process involved in outflow tract morphogenesis GO:1902257 9.37 FOXC1 FOXC2
25 lymphangiogenesis GO:0001946 9.33 FLT4 FOXC2 SOX18
26 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.26 FLT4 FOXC1 FOXC2 VEGFC
27 lymph vessel development GO:0001945 8.92 FLT4 FOXC1 FOXC2 SOX18
28 regulation of transcription, DNA-templated GO:0006355 10.02 FOXC1 FOXC2 FOXL1 PHF19 SOX18

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

# Name GO ID Score Top Affiliating Genes
1 transcription regulatory region DNA binding GO:0044212 9.43 FOXC1 FOXC2 SOX18
2 DNA-binding transcription factor activity GO:0003700 9.35 FOXC1 FOXC2 FOXL1 PHF19 SOX18
3 promoter-specific chromatin binding GO:1990841 9.32 FOXC1 FOXC2
4 DNA binding, bending GO:0008301 9.16 FOXC1 FOXL1
5 sequence-specific DNA binding GO:0043565 9.02 FOXC1 FOXC2 FOXL1 PHF19 SOX18

Sources for Hereditary Lymphedema

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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