MCID: HRD007
MIFTS: 34

Hereditary Lymphedema

Categories: 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 29 6 15
Milroy Disease 70

Classifications:



External Ids:

Disease Ontology 12 DOID:0050580
ICD9CM 34 757.0
SNOMED-CT 67 205542007
UMLS 70 C1313885 C1704423

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 ii and lymphatic malformation 5. An important gene associated with Hereditary Lymphedema is CELSR1 (Cadherin EGF LAG Seven-Pass G-Type Receptor 1). Affiliated tissues include legs, endothelial and eye, and related phenotype is mortality/aging.

Related Diseases for Hereditary 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 Hereditary Lymphedema via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 94)
# Related Disease Score Top Affiliating Genes
1 hereditary lymphedema ii 32.8 SOX18 FOXC2 FOXC1 FLT4 CCBE1
2 lymphatic malformation 5 32.3 SOX18 FOXC2 FLT4 CCBE1
3 yellow nail syndrome 32.1 SOX18 FOXC2 CCR6
4 lymphedema-distichiasis syndrome 31.8 SOX18 FOXL1 FOXC2-AS1 FOXC2 FOXC1 FLT4
5 hereditary lymphedema i 31.5 SOX18 PHF19 PCNP MTF2 MIR150 LRRC8C
6 congenital lymphedema 31.2 HNRNPH1 FOXC2 FLT4
7 primary lymphedema 31.0 FOXC2 FLT4
8 distichiasis 30.8 FOXL1 FOXC2-AS1 FOXC2 FOXC1
9 cholestasis-lymphedema syndrome 30.5 SOX18 CCBE1
10 lymphatic malformation 1 11.5
11 hereditary lymphedema ic 11.4
12 hereditary lymphedema ia 11.3
13 hereditary lymphedema id 11.3
14 hereditary lymphedema ib 11.3
15 lymphatic malformation 4 11.0
16 hypotrichosis-lymphedema-telangiectasia syndrome 10.4 SOX18 FOXC2 FLT4
17 klippel-trenaunay-weber syndrome 10.4 SOX18 FOXC2 FLT4
18 colonic benign neoplasm 10.4 KDM4C H2AC18 CCR6
19 weaver syndrome 10.4 MTF2 KDM4C H2AC18
20 mature t-cell and nk-cell lymphoma 10.4 KDM4C H2AC18 CCR6
21 testicular disease 10.4 KDM4C H2AC18 CCR6
22 hypotrichosis 1 10.3 KDM4C H2AC18 CCR6
23 cardiovascular organ benign neoplasm 10.3 KDM4C H2AC18 FLT4 CCR6
24 lymphangioma 10.3 KDM4C H2AC18 FLT4 CCR6
25 mature b-cell neoplasm 10.3 KDM4C H2AC18 CCR6
26 autoimmune disease of gastrointestinal tract 10.3 MIR150 H2AC18 CCR6
27 chylothorax, congenital 10.3 SOX18 FOXC2 FLT4 CCBE1
28 corneal disease 10.3 H2AC18 FOXC1 CCR6
29 hennekam syndrome 10.3 SOX18 FOXC2 FLT4 CCBE1
30 bile duct adenocarcinoma 10.3 MIR150 KDM4C H2AC18 CCR6
31 bile duct disease 10.3 MIR150 KDM4C H2AC18 CCR6
32 biliary tract disease 10.3 MIR150 KDM4C H2AC18 CCR6
33 spinal disease 10.3 MIR150 KDM4C H2AC18 CCR6
34 connective tissue cancer 10.3 MIR150 KDM4C H2AC18 CCR6
35 bladder disease 10.3 MIR150 KDM4C H2AC18 CCR6
36 lymphatic system cancer 10.3 MIR150 KDM4C H2AC18 CCR6
37 autosomal genetic disease 10.3 MIR150 KDM4C H2AC18 CCR6
38 lymphatic system disease 10.3 MIR150 KDM4C H2AC18 CCR6
39 hair disease 10.3 SOX18 KDM4C H2AC18 CCR6
40 colonic disease 10.3 MIR150 KDM4C H2AC18 CCR6
41 chromosomal deletion syndrome 10.3 KDM4C H2AC18 CCR6
42 male reproductive organ cancer 10.3 MIR150 KDM4C H2AC18 CCR6
43 leukocyte disease 10.3 KDM4C H2AC18 CCR6
44 immune system disease 10.3 MIR150 KDM4C H2AC18 CCR6
45 male reproductive system disease 10.3 MIR150 KDM4C H2AC18 CCR6
46 malignant ovarian surface epithelial-stromal neoplasm 10.3 KDM4C H2AC18 CCR6
47 reproductive system disease 10.3 MIR150 KDM4C H2AC18 CCR6
48 urinary system disease 10.3 MIR150 KDM4C H2AC18 CCR6
49 large intestine cancer 10.3 MIR150 KDM4C H2AC18 CCR6
50 respiratory system cancer 10.3 MIR150 KDM4C H2AC18 CCR6

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 mortality/aging MP:0010768 9.44 CCBE1 CELSR1 EDN2 FLT4 FOXC1 FOXC2

Drugs & Therapeutics for Hereditary Lymphedema

Search Clinical Trials , NIH Clinical Center for Hereditary Lymphedema

Genetic Tests for Hereditary Lymphedema

Genetic tests related to Hereditary Lymphedema:

# Genetic test Affiliating Genes
1 Hereditary Lymphedema 29

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
Endothelial, Eye, Ovary, Skin, Liver

Publications for Hereditary Lymphedema

Articles related to Hereditary Lymphedema:

(show top 50) (show all 134)
# Title Authors PMID Year
1
A Case of Elephantiasis Nostras Verrucosa Secondary to Lymphedema Praecox Complicated by Congestive Cardiac Failure. 61
33714971 2021
2
De novo novel splice-site mutation in FLT4/VEGFR3 is associated with Milroy disease. 61
32991753 2021
3
The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases. 61
33067626 2020
4
Investigation on the role of biallelic variants in VEGF-C found in a patient affected by Milroy-like lymphedema. 61
32592340 2020
5
Surgical treatment of Milroy disease. 61
31165487 2020
6
Lymphoscintigraphic Abnormalities Associated with Milroy Disease and Lymphedema-Distichiasis Syndrome. 61
31721633 2019
7
Sex-limited penetrance of lymphedema to females with CELSR1 haploinsufficiency: A second family. 61
31403174 2019
8
Increasing evidence of hereditary lymphedema caused by CELSR1 loss-of-function variants. 61
31215153 2019
9
Rare genetic variants potentially involved in ovarian hyperstimulation syndrome. 61
30483911 2019
10
Cystic Hygroma: A Preliminary Genetic Study and a Short Review from the Literature. 61
30475086 2019
11
Whole Exome Sequencing Reveals the Major Genetic Contributors to Nonsyndromic Tetralogy of Fallot. 61
30582441 2019
12
Immunohistochemical Evaluation of Histological Change in a Chinese Milroy Disease Family With Venous and Skin Abnormities. 61
30941160 2019
13
Hamartomas and malformations of the liver. 61
30579648 2019
14
From fish embryos to human patients: lymphangiogenesis in development and disease. 61
29800868 2018
15
A novel mutation in the conserved sequence of vascular endothelial growth factor receptor 3 leads to primary lymphoedema. 61
29896974 2018
16
A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon. 61
30071673 2018
17
Further delineation of the SOX18-related Hypotrichosis, Lymphedema, Telangiectasia syndrome (HTLS). 61
29307792 2018
18
Modified enteromesenteric bridging operation for primary lymphedema. 61
30337509 2018
19
Hereditary Lymphedema of the Leg - A Case Report. 61
28785330 2017
20
[Primary lymphedema due to Milroy disease]. 61
26818397 2017
21
Atypical retiform hemangioendothelioma arising in a patient with Milroy disease: a case report and review of the literature. 61
27730656 2017
22
[Primary congenital lymphedema: Milroy disease: the first case observed in the Department of Pediatrics at the University Hospital Yalgado Ouedraogo, Ouagadougou]. 61
28748022 2017
23
In silico analysis of single nucleotide polymorphisms (SNPs) in human FOXC2 gene. 61
29511529 2017
24
Rare Variants in LAMA5 Gene associated with FLT4 and FOXC2 Mutations in Primary Lymphedema May Contribute to Severity. 61
29908552 2016
25
Milroy Disease or Primary Congenital Lymphedema Associated With Invasive Squamous Cell Carcinoma. 61
27374380 2016
26
A novel mutation in CELSR1 is associated with hereditary lymphedema. 61
26855770 2016
27
Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities. 61
26275891 2015
28
Excision of Elephantiasis Nostras Verrucosa Lesions in a Patient With Hereditary Lymphedema: Case Report and Review of the Literature. 61
25441846 2015
29
A Novel Missense Mutation in FLT4 Causes Autosomal Recessive Hereditary Lymphedema. 61
26091405 2015
30
Antenatal presentation of hereditary lymphedema type I. 61
25896638 2015
31
A NOVEL FLT4 GENE MUTATION AND MR LYMPHANGIOGRAPHY IN A CHINESE FAMILY WITH MILROY DISEASE. 61
26714373 2015
32
Stewart-Treves Syndrome of the Lower Extremity. 61
26312726 2015
33
Hereditary lymphedema, characteristics, and variations in 17 adult patients with lymphedema cholestasis syndrome 1/Aagenaes syndrome. 61
25317502 2014
34
A novel stop mutation in the vascular endothelial growth factor-C gene (VEGFC) results in Milroy-like disease. 61
24744435 2014
35
A novel FLT4 mutation identified in a patient with Milroy disease. 61
25109169 2014
36
Arap3 is dysregulated in a mouse model of hypotrichosis-lymphedema-telangiectasia and regulates lymphatic vascular development. 61
24163130 2014
37
AA amyloidosis as a complication of primary lymphedema. 61
23964754 2014
38
Regulation of lymphatic vascular morphogenesis: Implications for pathological (tumor) lymphangiogenesis. 61
23395992 2013
39
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
40
FLT4/VEGFR3 and Milroy disease: novel mutations, a review of published variants and database update. 61
23074044 2013
41
Four generations of rare familial lymphedema (Milroy disease). 61
23751338 2013
42
[Congenital Milroy Oedema: a case report of a family]. 61
22730636 2012
43
Hydrops fetalis and pulmonary lymphangiectasia due to FOXC2 mutation: an autosomal dominant hereditary lymphedema syndrome with variable expression. 61
21918810 2012
44
Genome-wide gene expression analysis implicates the immune response and lymphangiogenesis in the pathogenesis of fetal chylothorax. 61
22529953 2012
45
Prenatal diagnosis of Milroy disease. 61
22021048 2011
46
[Identification of VEGFR3 gene mutation in a Chinese family with autosomal dominant primary congenital lymphoedema]. 61
20677139 2010
47
Milroy's primary congenital lymphedema in a male infant and review of the literature. 61
20555004 2010
48
A new classification system for primary lymphatic dysplasias based on phenotype. 61
20447153 2010
49
Lymphatic dysfunction, not aplasia, underlies Milroy disease. 61
20536741 2010
50
Rare association of immunoglobulin A nephropathy and lymphedema-distichiasis syndrome. 61
20124880 2010

Variations for Hereditary Lymphedema

ClinVar genetic disease variations for Hereditary Lymphedema:

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

Expression for Hereditary Lymphedema

Search GEO for disease gene expression data for Hereditary Lymphedema.

Pathways for Hereditary Lymphedema

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 ESC/E(Z) complex GO:0035098 8.96 PHF19 MTF2
2 ion channel complex GO:0034702 8.62 LRRC8C LRRC8A

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

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 angiogenesis GO:0001525 9.86 SOX18 FOXC1 FLT4 CCBE1
2 heart development GO:0007507 9.85 SOX18 FOXL1 FOXC2 FOXC1
3 positive regulation of endothelial cell migration GO:0010595 9.69 FOXC2 FLT4 CCBE1
4 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.65 FOXC2 FOXC1 FLT4
5 anatomical structure morphogenesis GO:0009653 9.62 SOX18 FOXL1 FOXC2 FOXC1
6 blood vessel development GO:0001568 9.61 SOX18 FOXC2 FOXC1
7 vascular endothelial growth factor signaling pathway GO:0038084 9.58 FOXC1 FLT4
8 respiratory system process GO:0003016 9.58 FLT4 CCBE1
9 cardiac muscle cell proliferation GO:0060038 9.57 FOXC2 FOXC1
10 regulation of organ growth GO:0046620 9.54 FOXC2 FOXC1
11 aspartate transmembrane transport GO:0015810 9.52 LRRC8C LRRC8A
12 protein hexamerization GO:0034214 9.49 LRRC8C LRRC8A
13 paraxial mesoderm formation GO:0048341 9.46 FOXC2 FOXC1
14 taurine transport GO:0015734 9.4 LRRC8C LRRC8A
15 positive regulation of histone H3-K27 methylation GO:0061087 9.37 PHF19 MTF2
16 embryonic heart tube development GO:0035050 9.33 SOX18 FOXC2 FOXC1
17 negative regulation of apoptotic process involved in outflow tract morphogenesis GO:1902257 9.26 FOXC2 FOXC1
18 lymphangiogenesis GO:0001946 9.26 SOX18 FOXC2 FLT4 CCBE1
19 lymph vessel development GO:0001945 9.02 SOX18 FOXC2 FOXC1 FLT4 CCBE1

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

# Name GO ID Score Top Affiliating Genes
1 DNA binding, bending GO:0008301 8.96 FOXL1 FOXC1
2 volume-sensitive anion channel activity GO:0005225 8.62 LRRC8C LRRC8A

Sources for Hereditary 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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