MCID: HRD007
MIFTS: 37

Hereditary Lymphedema

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

Aliases & Classifications for Hereditary Lymphedema

MalaCards integrated aliases for Hereditary Lymphedema:

Name: Hereditary Lymphedema 12 36 6 15
Milroy Disease 71

Classifications:



External Ids:

Disease Ontology 12 DOID:0050580
KEGG 36 H00535
ICD9CM 34 757.0
SNOMED-CT 67 75127007
UMLS 71 C1313885 C1704423

Summaries for Hereditary Lymphedema

KEGG : 36 Hereditary lymphedema (LMPH) is a developmental disorder characterized by chronic lesions of the extremities due to insufficient lymphatic drainage. The dilated lymphatic channels that are not connected to the lymphatic vessels cause these edemas.

MalaCards based summary : Hereditary Lymphedema, also known as milroy disease, is related to hereditary lymphedema ii and lymphatic malformation 5. An important gene associated with Hereditary Lymphedema is CELSR1 (Cadherin EGF LAG Seven-Pass G-Type Receptor 1), and among its related pathways/superpathways are MAPK signaling pathway and Focal adhesion. Affiliated tissues include legs, skin and endothelial, and related phenotypes are growth/size/body region and digestive/alimentary

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

Wikipedia : 74 Milroy's disease (MD) is a familial disease characterized by lymphedema, commonly in the legs, caused by... 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
Primary Lymphedema Celsr1-Related Late-Onset Primary Lymphedema
Gjc2-Related Late-Onset Primary Lymphedema

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

(show top 50) (show all 60)
# Related Disease Score Top Affiliating Genes
1 hereditary lymphedema ii 34.6 SOX18 FOXC2 FOXC1 FLT4
2 lymphatic malformation 5 33.2 SOX18 FOXC2
3 lymphedema-distichiasis syndrome 33.1 FOXL1 FOXC2
4 yellow nail syndrome 32.5 SOX18 FOXC2
5 hereditary lymphedema i 32.5 TSPO SOX18 PRDM10 PHF19 PCNP PCLO
6 lymphedema 31.7 SOX18 FOXC2 FLT4
7 congenital lymphedema 31.4 HNRNPH1 FOXC2 FLT4
8 primary lymphedema 31.2 FOXC2 FLT4
9 distichiasis 31.0 FOXL1 FOXC2 FOXC1
10 hereditary lymphedema ic 12.5
11 hereditary lymphedema ia 12.5
12 hereditary lymphedema id 12.5
13 hereditary lymphedema ib 12.5
14 lymphatic malformation 1 12.0
15 lymphatic malformation 4 11.2
16 b-cell childhood acute lymphoblastic leukemia 10.5 SOX18 KDM4C
17 chylothorax, congenital 10.5 SOX18 FOXC2 FLT4
18 hennekam syndrome 10.5 SOX18 FOXC2 FLT4
19 klippel-trenaunay-weber syndrome 10.4 SOX18 FOXC2 FLT4
20 bile duct adenocarcinoma 10.4 MIR150 KDM4C H2AC18
21 hypotrichosis 1 10.4 PRDM10 KDM4C H2AC18
22 bile duct disease 10.4 MIR150 KDM4C H2AC18
23 corneal disease 10.4 PRDM10 H2AC18 FOXC1
24 autosomal genetic disease 10.3 PRDM10 MIR150 KDM4C H2AC18
25 biliary tract disease 10.3 MIR150 KDM4C H2AC18
26 pontocerebellar hypoplasia 10.3 PCLO KDM4C H2AC18
27 hair disease 10.3 SOX18 PRDM10 KDM4C H2AC18
28 kabuki syndrome 1 10.3 PRDM10 KDM4C H2AC18
29 hydrops, lactic acidosis, and sideroblastic anemia 10.3
30 eye disease 10.2 PRDM10 KDM4C H2AC18 FOXC1 FLT4
31 specific developmental disorder 10.2 PRDM10 KDM4C H2AC18
32 lymphatic system disease 10.2 SOX18 MIR150 KDM4C H2AC18 FOXC2 FLT4
33 autonomic nervous system neoplasm 10.2 PRDM10 KDM4C H2AC18
34 hypotrichosis 10.2 SOX18 PRDM10 KDM4C H2AC18 FOXC2 FLT4
35 hydrops fetalis, nonimmune 10.1
36 peripheral nervous system neoplasm 10.1 PRDM10 KDM4C H2AC18
37 lymphangiosarcoma 10.1
38 cholestasis-lymphedema syndrome 10.0
39 gonadal dysgenesis 10.0
40 papilloma 10.0
41 elephantiasis 10.0
42 contractures, pterygia, and variable skeletal fusions syndrome 1a 9.9 PRDM10 KDM4C H2AC18
43 angioedema, hereditary, type i 9.8
44 cleft palate, isolated 9.8
45 kaposi sarcoma 9.8
46 ascites, chylous 9.8
47 respiratory failure 9.8
48 erysipelas 9.8
49 cholestasis 9.8
50 obstructive jaundice 9.8

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:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.77 ACD CELSR1 EDN2 FLT4 FOXC1 FOXC2
2 digestive/alimentary MP:0005381 9.7 ACD EDN2 FLT4 FOXC1 FOXC2 FOXL1
3 mortality/aging MP:0010768 9.5 ACD CELSR1 EDN2 FLT4 FOXC1 FOXC2

Drugs & Therapeutics for Hereditary Lymphedema

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase I/II Combinational Investigational New Drug Application: 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:

40
Skin, Endothelial, Liver, Testes, Eye, B Cells

Publications for Hereditary Lymphedema

Articles related to Hereditary Lymphedema:

(show top 50) (show all 130)
# Title Authors PMID Year
1
Surgical treatment of Milroy disease. 61
31165487 2020
2
Lymphoscintigraphic Abnormalities Associated with Milroy Disease and Lymphedema-Distichiasis Syndrome. 61
31721633 2019
3
Sex-limited penetrance of lymphedema to females with CELSR1 haploinsufficiency: A second family. 61
31403174 2019
4
Increasing evidence of hereditary lymphedema caused by CELSR1 loss-of-function variants. 61
31215153 2019
5
Rare genetic variants potentially involved in ovarian hyperstimulation syndrome. 61
30483911 2019
6
Whole Exome Sequencing Reveals the Major Genetic Contributors to Nonsyndromic Tetralogy of Fallot. 61
30582441 2019
7
Cystic Hygroma: A Preliminary Genetic Study and a Short Review from the Literature. 61
30475086 2019
8
Hamartomas and malformations of the liver. 61
30579648 2019
9
Immunohistochemical Evaluation of Histological Change in a Chinese Milroy Disease Family With Venous and Skin Abnormities. 61
30941160 2019
10
A novel mutation in the conserved sequence of vascular endothelial growth factor receptor 3 leads to primary lymphoedema. 61
29896974 2018
11
From fish embryos to human patients: lymphangiogenesis in development and disease. 61
29800868 2018
12
A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon. 61
30071673 2018
13
Further delineation of the SOX18-related Hypotrichosis, Lymphedema, Telangiectasia syndrome (HTLS). 61
29307792 2018
14
Modified enteromesenteric bridging operation for primary lymphedema. 61
30337509 2018
15
Hereditary Lymphedema of the Leg - A Case Report. 61
28785330 2017
16
[Primary lymphedema due to Milroy disease]. 61
26818397 2017
17
Atypical retiform hemangioendothelioma arising in a patient with Milroy disease: a case report and review of the literature. 61
27730656 2017
18
[Primary congenital lymphedema: Milroy disease: the first case observed in the Department of Pediatrics at the University Hospital Yalgado Ouedraogo, Ouagadougou]. 61
28748022 2017
19
In silico analysis of single nucleotide polymorphisms (SNPs) in human FOXC2 gene. 61
29511529 2017
20
Milroy Disease or Primary Congenital Lymphedema Associated With Invasive Squamous Cell Carcinoma. 61
27374380 2016
21
Rare Variants in LAMA5 Gene associated with FLT4 and FOXC2 Mutations in Primary Lymphedema May Contribute to Severity. 61
29908552 2016
22
A novel mutation in CELSR1 is associated with hereditary lymphedema. 61
26855770 2016
23
Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities. 61
26275891 2015
24
Excision of Elephantiasis Nostras Verrucosa Lesions in a Patient With Hereditary Lymphedema: Case Report and Review of the Literature. 61
25441846 2015
25
A Novel Missense Mutation in FLT4 Causes Autosomal Recessive Hereditary Lymphedema. 61
26091405 2015
26
Antenatal presentation of hereditary lymphedema type I. 61
25896638 2015
27
A NOVEL FLT4 GENE MUTATION AND MR LYMPHANGIOGRAPHY IN A CHINESE FAMILY WITH MILROY DISEASE. 61
26714373 2015
28
Stewart-Treves Syndrome of the Lower Extremity. 61
26312726 2015
29
Hereditary lymphedema, characteristics, and variations in 17 adult patients with lymphedema cholestasis syndrome 1/Aagenaes syndrome. 61
25317502 2014
30
A novel stop mutation in the vascular endothelial growth factor-C gene (VEGFC) results in Milroy-like disease. 61
24744435 2014
31
A novel FLT4 mutation identified in a patient with Milroy disease. 61
25109169 2014
32
Arap3 is dysregulated in a mouse model of hypotrichosis-lymphedema-telangiectasia and regulates lymphatic vascular development. 61
24163130 2014
33
AA amyloidosis as a complication of primary lymphedema. 61
23964754 2014
34
Regulation of lymphatic vascular morphogenesis: Implications for pathological (tumor) lymphangiogenesis. 61
23395992 2013
35
Mutation in vascular endothelial growth factor-C, a ligand for vascular endothelial growth factor receptor-3, is associated with autosomal dominant milroy-like primary lymphedema. 61
23410910 2013
36
FLT4/VEGFR3 and Milroy disease: novel mutations, a review of published variants and database update. 61
23074044 2013
37
Four generations of rare familial lymphedema (Milroy disease). 61
23751338 2013
38
[Congenital Milroy Oedema: a case report of a family]. 61
22730636 2012
39
Hydrops fetalis and pulmonary lymphangiectasia due to FOXC2 mutation: an autosomal dominant hereditary lymphedema syndrome with variable expression. 61
21918810 2012
40
Genome-wide gene expression analysis implicates the immune response and lymphangiogenesis in the pathogenesis of fetal chylothorax. 61
22529953 2012
41
Prenatal diagnosis of Milroy disease. 61
22021048 2011
42
[Identification of VEGFR3 gene mutation in a Chinese family with autosomal dominant primary congenital lymphoedema]. 61
20677139 2010
43
Lymphatic dysfunction, not aplasia, underlies Milroy disease. 61
20536741 2010
44
A new classification system for primary lymphatic dysplasias based on phenotype. 61
20447153 2010
45
Milroy's primary congenital lymphedema in a male infant and review of the literature. 61
20555004 2010
46
Rare association of immunoglobulin A nephropathy and lymphedema-distichiasis syndrome. 61
20124880 2010
47
Purpura-associated congenital lymphedema. 61
19620038 2009
48
Puffy feet in an 11-month-old infant: a quiz. Milroy disease. 61
19997714 2009
49
Recessive primary congenital lymphoedema caused by a VEGFR3 mutation. 61
19289394 2009
50
Analysis of the coding regions of VEGFR3 and VEGFC in Milroy disease and other primary lymphoedemas. 61
19002718 2009

Variations for Hereditary Lymphedema

ClinVar genetic disease variations for Hereditary Lymphedema:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CELSR1 NM_014246.3(CELSR1):c.5226+2T>ASNV Pathogenic 598932 rs1569141899 22:46804891-46804891 22:46408994-46408994
2 CELSR1 NM_014246.3(CELSR1):c.6739+1G>ASNV Pathogenic 598933 rs1569124017 22:46782298-46782298 22:46386401-46386401
3 CELSR1 NM_014246.3(CELSR1):c.868G>T (p.Glu290Ter)SNV Likely pathogenic 590904 rs1569227576 22:46932200-46932200 22:46536303-46536303
4 CELSR1 NM_014246.3(CELSR1):c.5702-1G>CSNV Likely pathogenic 598923 rs1569133268 22:46792644-46792644 22:46396747-46396747
5 CELSR1 NM_014246.3(CELSR1):c.2042del (p.Asn681fs)deletion Likely pathogenic 598924 rs1569226110 22:46931026-46931026 22:46535129-46535129

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 COSM84061323 GNA11 soft tissue,leg,haemangioma,congenital c.626A>C p.Q209P 19:3118944-3118944 4

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:

36
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 Focal adhesion hsa04510
3 PI3K-Akt signaling pathway hsa04151
4 Rap1 signaling pathway hsa04015

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 nuclear chromatin GO:0000790 9.43 SOX18 KDM4C H2AC18 FOXL1 FOXC2 FOXC1
2 nucleoplasm GO:0005654 9.36 PHF19 PCNP MTF2 KDM4C HNRNPH1 FOXC2
3 ESC/E(Z) complex GO:0035098 9.16 PHF19 MTF2

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

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription, DNA-templated GO:0045893 9.95 SOX18 PHF19 MTF2 FOXC2 FOXC1
2 heart development GO:0007507 9.8 SOX18 FOXL1 FOXC2 FOXC1
3 anatomical structure morphogenesis GO:0009653 9.71 FOXL1 FOXC2 FOXC1
4 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.63 FOXC2 FOXC1 FLT4
5 stem cell population maintenance GO:0019827 9.58 PHF19 MTF2 KDM4C
6 regulation of blood vessel diameter GO:0097746 9.56 FOXC2 FOXC1
7 blood vessel development GO:0001568 9.54 SOX18 FOXC2 FOXC1
8 vascular endothelial growth factor signaling pathway GO:0038084 9.52 FOXC1 FLT4
9 cardiac muscle cell proliferation GO:0060038 9.51 FOXC2 FOXC1
10 regulation of organ growth GO:0046620 9.48 FOXC2 FOXC1
11 paraxial mesoderm formation GO:0048341 9.43 FOXC2 FOXC1
12 embryonic heart tube development GO:0035050 9.33 SOX18 FOXC2 FOXC1
13 positive regulation of histone H3-K27 methylation GO:0061087 9.32 PHF19 MTF2
14 negative regulation of apoptotic process involved in outflow tract morphogenesis GO:1902257 9.26 FOXC2 FOXC1
15 lymphangiogenesis GO:0001946 9.13 SOX18 FOXC2 FLT4
16 lymph vessel development GO:0001945 8.92 SOX18 FOXC2 FOXC1 FLT4

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 GO:0003700 9.43 SOX18 PHF19 MTF2 FOXL1 FOXC2 FOXC1
2 DNA binding, bending GO:0008301 9.16 FOXL1 FOXC1
3 sequence-specific DNA binding GO:0043565 9.1 SOX18 PHF19 MTF2 FOXL1 FOXC2 FOXC1

Sources for Hereditary 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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