MCID: HRD007
MIFTS: 39

Hereditary Lymphedema

Categories: Blood diseases, Cancer diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Hereditary Lymphedema

MalaCards integrated aliases for Hereditary Lymphedema:

Name: Hereditary Lymphedema 12 38 15
Milroy Disease 74

Classifications:



External Ids:

Disease Ontology 12 DOID:0050580
KEGG 38 H00535
ICD9CM 36 757.0
SNOMED-CT 69 75127007

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 milroy disease, is related to hereditary lymphedema i and lymphedema-distichiasis syndrome. 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 Cytochrome P-450 Enzyme Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include legs and breast, and related phenotypes are cardiovascular system and digestive/alimentary

Wikipedia : 77 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:

Hereditary Lymphedema Hereditary Lymphedema Ic
Hereditary Lymphedema Id Hereditary Lymphedema Ia
Hereditary Lymphedema Ib Hereditary Lymphedema I
Hereditary Lymphedema Ii Congenital Lymphedema

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

(show all 37)
# Related Disease Score Top Affiliating Genes
1 hereditary lymphedema i 33.2 CHMP1A FLT4 PHF19 SOX18
2 lymphedema-distichiasis syndrome 32.4 FOXC2 FOXL1
3 yellow nail syndrome 31.8 FOXC2 SOX18
4 lymphedema 30.3 FLT4 FOXC2 SOX18 VEGFC
5 lymphangiosarcoma 30.0 FLT4 VEGFC
6 distichiasis 29.7 CHMP1A FOXC1 FOXC2 FOXL1
7 hereditary lymphedema ii 12.4
8 hereditary lymphedema ic 12.3
9 hereditary lymphedema id 12.3
10 hereditary lymphedema ia 12.3
11 hereditary lymphedema ib 12.3
12 lymphatic malformation 1 11.5
13 lymphatic malformation 5 11.1
14 lymphatic malformation 4 11.1
15 chylothorax, congenital 10.2 FLT4 FOXC2
16 syngnathia 10.1 FOXC1 FOXC2
17 gorham's disease 10.1 FLT4 VEGFC
18 congenital hydrocephalus 10.0 FOXC1 FOXL1
19 hennekam syndrome 10.0 FLT4 VEGFC
20 lymphangioma 10.0 FLT4 VEGFC
21 klippel-trenaunay-weber syndrome 9.9 FLT4 FOXC2 SOX18
22 venous malformations, multiple cutaneous and mucosal 9.9 FLT4 FOXC2 SOX18
23 lymphatic system disease 9.9 FLT4 FOXC2 VEGFC
24 breast carcinoma in situ 9.9 FLT4 VEGFC
25 hypoplastic left heart syndrome 9.8 FOXC2 FOXL1
26 angioedema, hereditary, type i 9.8
27 cholestasis-lymphedema syndrome 9.8
28 lymphatic malformation 7 9.8
29 diabetes mellitus 9.8
30 cholestasis 9.8
31 obstructive jaundice 9.8
32 elephantiasis 9.8
33 fetal edema 9.8
34 hemangioendothelioma 9.8
35 hydrops fetalis 9.8
36 kaposiform hemangioendothelioma 9.8
37 congenital lymphedema 9.7 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:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.5 CAMTA2 FLT4 FOXC1 FOXC2 PHF19 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 25)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Paroxetine Approved, Investigational Phase 3 61869-08-7 43815
2 Cytochrome P-450 Enzyme Inhibitors Phase 3
3 Antidepressive Agents Phase 3
4 Neurotransmitter Uptake Inhibitors Phase 3
5 Antidepressive Agents, Second-Generation Phase 3
6 Psychotropic Drugs Phase 3
7 Neurotransmitter Agents Phase 3,Phase 2
8 Serotonin Agents Phase 3
9 Serotonin Uptake Inhibitors Phase 3
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 Adrenergic Agents Phase 2
15 Antihypertensive Agents Phase 2
16 Anti-Arrhythmia Agents Phase 2
17 Adrenergic beta-Antagonists Phase 2
18 Vasodilator Agents Phase 2
19 Adrenergic Antagonists Phase 2
20 interferons Phase 2
21 Interferon Inducers Phase 2
22 Adjuvants, Immunologic Phase 2
23 Immunologic Factors Phase 2
24 Anesthetics
25 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 Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment Unknown status NCT01273909
6 Validation of Metrological Properties of Lymphoqol Unknown status NCT01922635 Not Applicable
7 Validation of a New Method of Limb Volumetry Unknown status NCT01574911
8 Out-of Pocket Payments in Patients With Lymphedema Completed NCT02988479
9 Out-of Pocket Payments With Lymphedema in France Completed NCT02988505
10 Physical Therapies in the Decongestive Treatment of Lymphedema Completed NCT01748604 Not Applicable
11 Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders Enrolling by invitation NCT00833599 NIRFLI with ICG
12 Histologic Analysis of the Lymphatic Vessels Used for Supermicrosurgical Lymphatico-venous Anastomoses in Lymphedema Recruiting NCT03465930
13 Oedema Study : Chroedem Recruiting NCT02914808
14 A Pilot Study to Evaluate the Feasibility and Potential Effectiveness of the Flexitouch System Head and Neck Treatment Recruiting NCT03332160 Not Applicable
15 Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced Pneumatic Compression Device (PCD) Recruiting NCT02661646

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:

20
Legs

MalaCards organs/tissues related to Hereditary Lymphedema:

42
Breast

Publications for Hereditary Lymphedema

Articles related to Hereditary Lymphedema:

(show all 40)
# 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
Prenatal diagnosis of Milroy disease. ( 22021048 )
2011
9
Lymphatic dysfunction, not aplasia, underlies Milroy disease. ( 20536741 )
2010
10
Puffy feet in an 11-month-old infant: a quiz. Milroy disease. ( 19997714 )
2009
11
Identification of a novel VEGFR-3 missense mutation in a Chinese family with hereditary lymphedema type I. ( 17945164 )
2007
12
Three children with Milroy disease and de novo mutations in VEGFR3. ( 17250670 )
2007
13
Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations. ( 16965327 )
2006
14
Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3. ( 16924388 )
2006
15
Clinical variability in a Japanese hereditary lymphedema type I family with an FLT4 mutation. ( 15904433 )
2005
16
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
17
Stewart-Treves syndrome as a rare complication of a hereditary lymphedema. ( 15061047 )
2004
18
A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus. ( 15523639 )
2004
19
Kaposiform hemangioendothelioma associated with Milroy's disease (primary hereditary lymphedema). ( 12861592 )
2003
20
Syndromic classification of hereditary lymphedema. ( 14992570 )
2003
21
Age of onset in hereditary lymphedema. ( 12838201 )
2003
22
Verruciform xanthoma in association with milroy disease and leaky capillary syndrome. ( 12558846 )
2003
23
A model for gene therapy of human hereditary lymphedema. ( 11592985 )
2001
24
Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. ( 10856194 )
2000
25
Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. ( 11078474 )
2000
26
Hereditary lymphedema: evidence for linkage and genetic heterogeneity. ( 9817924 )
1998
27
Lymphangiosarcoma of the pubic region: a rare complication arising in congenital non-hereditary lymphedema. ( 9854166 )
1998
28
Lymphangiosarcoma in late-onset hereditary lymphedema: case report and nosological implications. ( 7747790 )
1995
29
Hereditary lymphedema and distichiasis. ( 2064580 )
1991
30
Hereditary lymphedema in Hereford cattle. ( 2039787 )
1991
31
Congenital hereditary lymphedema (Nonne/Milroy). ( 2616174 )
1989
32
Scintilymphangiography with 99 mTc-antimony sulfide colloid in hereditary lymphedema (Nonne-Milroy diseases). ( 709985 )
1978
33
Congenital hereditary lymphedema in the pig. ( 642582 )
1978
34
The pathogenesis of congenital hereditary lymphedema in the pig. ( 642583 )
1978
35
Chronic hereditary lymphedema of the legs with congenital conjunctival lymphedema. ( 5020171 )
1972
36
Hereditary lymphedema and obstructive jaundice. ( 5544157 )
1971
37
PLEURAL EFFUSION IN CHRONIC HEREDITARY LYMPHEDEMA (NONNE, MILROY, MEIGE'S DISEASE). REPORT OF TWO CASES. ( 14115303 )
1964
38
Genetic and physiological aspects of a family with chronic hereditary lymphedema (Nonne-Milroy-Meige's disease) and hereditary angioneurotic edema. ( 13533392 )
1958
39
Prednisone in the management of idiopathic hereditary lymphedema (Milroy's disease). ( 13345610 )
1956
40
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 0

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:

38
# 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 10.46 FOXC1 FOXC2 VEGFC
2 10.32 FLT4 VEGFC

GO Terms for Hereditary Lymphedema

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

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.28 CAMTA2 CHMP1A FLT4 FOXC1 FOXC2 FOXL1

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

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.92 FOXC1 FOXC2 FOXL1 SOX18
2 positive regulation of transcription, DNA-templated GO:0045893 9.9 FOXC1 FOXC2 PHF19 SOX18
3 cell differentiation GO:0030154 9.8 FOXC1 FOXC2 FOXL1 SOX18 VEGFC
4 heart development GO:0007507 9.78 FOXC1 FOXC2 FOXL1 SOX18
5 angiogenesis GO:0001525 9.76 FLT4 FOXC1 SOX18 VEGFC
6 anatomical structure morphogenesis GO:0009653 9.7 FOXC1 FOXC2 FOXL1
7 somitogenesis GO:0001756 9.64 FOXC1 FOXC2
8 positive regulation of endothelial cell migration GO:0010595 9.63 FLT4 FOXC2
9 heart morphogenesis GO:0003007 9.63 FOXC1 FOXC2
10 collagen fibril organization GO:0030199 9.62 FOXC1 FOXC2
11 ureteric bud development GO:0001657 9.61 FOXC1 FOXC2
12 blood vessel remodeling GO:0001974 9.61 FOXC1 FOXC2
13 blood vessel development GO:0001568 9.61 FOXC1 FOXC2 SOX18
14 sprouting angiogenesis GO:0002040 9.59 FLT4 VEGFC
15 vasculature development GO:0001944 9.58 FLT4 SOX18
16 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.58 FOXC1 FOXC2
17 artery morphogenesis GO:0048844 9.57 FOXC1 FOXC2
18 neural crest cell development GO:0014032 9.56 FOXC1 FOXC2
19 regulation of blood vessel size GO:0050880 9.55 FOXC1 FOXC2
20 cardiac muscle cell proliferation GO:0060038 9.54 FOXC1 FOXC2
21 regulation of organ growth GO:0046620 9.51 FOXC1 FOXC2
22 embryonic heart tube development GO:0035050 9.5 FOXC1 FOXC2 SOX18
23 paraxial mesoderm formation GO:0048341 9.49 FOXC1 FOXC2
24 vascular endothelial growth factor signaling pathway GO:0038084 9.43 FLT4 FOXC1 VEGFC
25 negative regulation of apoptotic process involved in outflow tract morphogenesis GO:1902257 9.37 FOXC1 FOXC2
26 lymphangiogenesis GO:0001946 9.33 FLT4 FOXC2 SOX18
27 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.26 FLT4 FOXC1 FOXC2 VEGFC
28 lymph vessel development GO:0001945 8.92 FLT4 FOXC1 FOXC2 SOX18

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

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.77 CAMTA2 FOXC1 FOXC2 FOXL1 SOX18
2 transcription regulatory region DNA binding GO:0044212 9.43 FOXC1 FOXC2 SOX18
3 DNA-binding transcription factor activity GO:0003700 9.35 FOXC1 FOXC2 FOXL1 PHF19 SOX18
4 promoter-specific chromatin binding GO:1990841 9.32 FOXC1 FOXC2
5 DNA binding, bending GO:0008301 9.16 FOXC1 FOXL1
6 sequence-specific DNA binding GO:0043565 9.1 CAMTA2 FOXC1 FOXC2 FOXL1 PHF19 SOX18

Sources for Hereditary Lymphedema

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....