MCID: HRD007
MIFTS: 41

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 6 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 CELSR1 (Cadherin EGF LAG Seven-Pass G-Type Receptor 1), 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 breast, skin and heart, 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 39)
# Related Disease Score Top Affiliating Genes
1 hereditary lymphedema i 33.5 FLT4 PHF19 SOX18
2 lymphedema-distichiasis syndrome 32.4 FOXC2 FOXL1
3 yellow nail syndrome 31.7 FOXC2 SOX18
4 distichiasis 30.2 FOXC1 FOXC2 FOXL1
5 lymphedema 30.0 FLT4 FOXC2 SOX18 VEGFC
6 lymphangiosarcoma 29.8 FLT4 VEGFC
7 hereditary lymphedema ii 12.5
8 hereditary lymphedema ic 12.4
9 hereditary lymphedema id 12.4
10 hereditary lymphedema ia 12.4
11 hereditary lymphedema ib 12.4
12 lymphatic malformation 1 11.8
13 lymphatic malformation 5 11.1
14 lymphatic malformation 4 11.1
15 chylothorax, congenital 10.2 FLT4 FOXC2
16 syngnathia 10.2 FOXC1 FOXC2
17 congenital hydrocephalus 10.0 FOXC1 FOXL1
18 gorham's disease 9.9 FLT4 VEGFC
19 hennekam syndrome 9.9 FLT4 VEGFC
20 klippel-trenaunay-weber syndrome 9.9 FLT4 FOXC2 SOX18
21 venous malformations, multiple cutaneous and mucosal 9.9 FLT4 FOXC2 SOX18
22 lymphangioma 9.9 FLT4 VEGFC
23 hypoplastic left heart syndrome 9.8 FOXC2 FOXL1
24 angioedema, hereditary, type i 9.8
25 cholestasis-lymphedema syndrome 9.8
26 lymphatic malformation 7 9.8
27 diabetes mellitus 9.8
28 cholestasis 9.8
29 obstructive jaundice 9.8
30 hereditary angioedema 9.8
31 elephantiasis 9.8
32 fetal edema 9.8
33 hemangioendothelioma 9.8
34 hydrops fetalis 9.8
35 kaposiform hemangioendothelioma 9.8
36 lymphangiectasis 9.8
37 lymphatic system disease 9.8 FLT4 FOXC2 VEGFC
38 breast carcinoma in situ 9.7 FLT4 VEGFC
39 congenital lymphedema 9.6 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 Neurotransmitter Uptake Inhibitors Phase 3
3 Cytochrome P-450 Enzyme Inhibitors Phase 3
4 Serotonin Uptake Inhibitors Phase 3
5 Antidepressive Agents, Second-Generation Phase 3
6 Cytochrome P-450 CYP2D6 Inhibitors Phase 3
7 Neurotransmitter Agents Phase 3,Phase 2
8 Antidepressive Agents Phase 3
9 Psychotropic Drugs Phase 3
10 Serotonin Agents 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 Antagonists Phase 2
15 Adrenergic Agents Phase 2
16 Vasodilator Agents Phase 2
17 Anti-Arrhythmia Agents Phase 2
18 Adrenergic beta-Antagonists Phase 2
19 Antihypertensive Agents Phase 2
20 Interferon Inducers Phase 2
21 Adjuvants, Immunologic Phase 2
22 Immunologic Factors Phase 2
23 interferons Phase 2
24 Anesthetics
25 Complement System Proteins

Interventional clinical trials:

(show all 14)
# 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 Propranolol Dose Escalation in Lymphedema in Patients Recruiting NCT02595996 Phase 2 Propranolol
3 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
4 Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment Unknown status NCT01273909
5 Validation of Metrological Properties of Lymphoqol Unknown status NCT01922635 Not Applicable
6 Validation of a New Method of Limb Volumetry Unknown status NCT01574911
7 Out-of Pocket Payments in Patients With Lymphedema Completed NCT02988479
8 Out-of Pocket Payments With Lymphedema in France Completed NCT02988505
9 Physical Therapies in the Decongestive Treatment of Lymphedema Completed NCT01748604 Not Applicable
10 Histologic Analysis of the Lymphatic Vessels Used for Supermicrosurgical Lymphatico-venous Anastomoses in Lymphedema Recruiting NCT03465930
11 Oedema Study : Chroedem Recruiting NCT02914808
12 A Pilot Study to Evaluate the Feasibility and Potential Effectiveness of the Flexitouch System Head and Neck Treatment Recruiting NCT03332160 Not Applicable
13 Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced Pneumatic Compression Device (PCD) Recruiting NCT02661646
14 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

MalaCards organs/tissues related to Hereditary Lymphedema:

42
Breast, Skin, Heart

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

20
Legs

Publications for Hereditary Lymphedema

Articles related to Hereditary Lymphedema:

(show all 50)
# Title Authors Year
1
Immunohistochemical Evaluation of Histological Change in a Chinese Milroy Disease Family With Venous and Skin Abnormities. ( 30941160 )
2019
2
Atypical retiform hemangioendothelioma arising in a patient with Milroy disease: a case report and review of the literature. ( 27730656 )
2017
3
Hereditary Lymphedema of the Leg - A Case Report. ( 28785330 )
2017
4
Milroy Disease or Primary Congenital Lymphedema Associated With Invasive Squamous Cell Carcinoma. ( 27374380 )
2016
5
A novel mutation in CELSR1 is associated with hereditary lymphedema. ( 26855770 )
2016
6
Excision of Elephantiasis Nostras Verrucosa Lesions in a Patient With Hereditary Lymphedema: Case Report and Review of the Literature. ( 25441846 )
2015
7
Antenatal presentation of hereditary lymphedema type I. ( 25896638 )
2015
8
A Novel Missense Mutation in FLT4 Causes Autosomal Recessive Hereditary Lymphedema. ( 26091405 )
2015
9
A NOVEL FLT4 GENE MUTATION AND MR LYMPHANGIOGRAPHY IN A CHINESE FAMILY WITH MILROY DISEASE. ( 26714373 )
2015
10
Hereditary lymphedema, characteristics, and variations in 17 adult patients with lymphedema cholestasis syndrome 1/Aagenaes syndrome. ( 25317502 )
2014
11
A novel FLT4 mutation identified in a patient with Milroy disease. ( 25109169 )
2014
12
Four generations of rare familial lymphedema (Milroy disease). ( 23751338 )
2013
13
FLT4/VEGFR3 and Milroy disease: novel mutations, a review of published variants and database update. ( 23074044 )
2013
14
Hydrops fetalis and pulmonary lymphangiectasia due to FOXC2 mutation: an autosomal dominant hereditary lymphedema syndrome with variable expression. ( 21918810 )
2012
15
Prenatal diagnosis of Milroy disease. ( 22021048 )
2011
16
Lymphatic dysfunction, not aplasia, underlies Milroy disease. ( 20536741 )
2010
17
Analysis of the coding regions of VEGFR3 and VEGFC in Milroy disease and other primary lymphoedemas. ( 19002718 )
2009
18
Puffy feet in an 11-month-old infant: a quiz. Milroy disease. ( 19997714 )
2009
19
Identification of a novel VEGFR-3 missense mutation in a Chinese family with hereditary lymphedema type I. ( 17945164 )
2007
20
Three children with Milroy disease and de novo mutations in VEGFR3. ( 17250670 )
2007
21
A novel VEGFR3 mutation causes Milroy disease. ( 17458866 )
2007
22
Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3. ( 16924388 )
2006
23
Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations. ( 16965327 )
2006
24
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
25
Clinical variability in a Japanese hereditary lymphedema type I family with an FLT4 mutation. ( 15904433 )
2005
26
Milroy disease and the VEGFR-3 mutation phenotype. ( 15689446 )
2005
27
A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus. ( 15523639 )
2004
28
Stewart-Treves syndrome as a rare complication of a hereditary lymphedema. ( 15061047 )
2004
29
Kaposiform hemangioendothelioma associated with Milroy's disease (primary hereditary lymphedema). ( 12861592 )
2003
30
Age of onset in hereditary lymphedema. ( 12838201 )
2003
31
Syndromic classification of hereditary lymphedema. ( 14992570 )
2003
32
Verruciform xanthoma in association with milroy disease and leaky capillary syndrome. ( 12558846 )
2003
33
A model for gene therapy of human hereditary lymphedema. ( 11592985 )
2001
34
Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. ( 11078474 )
2000
35
Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. ( 10856194 )
2000
36
Hereditary lymphedema: evidence for linkage and genetic heterogeneity. ( 9817924 )
1998
37
Lymphangiosarcoma of the pubic region: a rare complication arising in congenital non-hereditary lymphedema. ( 9854166 )
1998
38
Lymphangiosarcoma in late-onset hereditary lymphedema: case report and nosological implications. ( 7747790 )
1995
39
Hereditary lymphedema and distichiasis. ( 2064580 )
1991
40
Hereditary lymphedema in Hereford cattle. ( 2039787 )
1991
41
Congenital hereditary lymphedema (Nonne/Milroy). ( 2616174 )
1989
42
Congenital hereditary lymphedema in the pig. ( 642582 )
1978
43
The pathogenesis of congenital hereditary lymphedema in the pig. ( 642583 )
1978
44
Scintilymphangiography with 99 mTc-antimony sulfide colloid in hereditary lymphedema (Nonne-Milroy diseases). ( 709985 )
1978
45
Chronic hereditary lymphedema of the legs with congenital conjunctival lymphedema. ( 5020171 )
1972
46
Hereditary lymphedema and obstructive jaundice. ( 5544157 )
1971
47
PLEURAL EFFUSION IN CHRONIC HEREDITARY LYMPHEDEMA (NONNE, MILROY, MEIGE'S DISEASE). REPORT OF TWO CASES. ( 14115303 )
1964
48
Genetic and physiological aspects of a family with chronic hereditary lymphedema (Nonne-Milroy-Meige's disease) and hereditary angioneurotic edema. ( 13533392 )
1958
49
Prednisone in the management of idiopathic hereditary lymphedema (Milroy's disease). ( 13345610 )
1956
50
Chronic hereditary lymphedema (Nonne-Milroy-Meige's Disease). ( 15418956 )
1950

Variations for Hereditary Lymphedema

ClinVar genetic disease variations for Hereditary Lymphedema:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CELSR1 NM_014246.1(CELSR1): c.868G> T (p.Glu290Ter) single nucleotide variant Likely pathogenic GRCh38 Chromosome 22, 46536303: 46536303
2 CELSR1 NM_014246.1(CELSR1): c.868G> T (p.Glu290Ter) single nucleotide variant Likely pathogenic GRCh37 Chromosome 22, 46932200: 46932200
3 CELSR1 NM_014246.2(CELSR1): c.5702-1G> C single nucleotide variant Likely pathogenic GRCh37 Chromosome 22, 46792644: 46792644
4 CELSR1 NM_014246.2(CELSR1): c.5702-1G> C single nucleotide variant Likely pathogenic GRCh38 Chromosome 22, 46396747: 46396747
5 CELSR1 NM_014246.2(CELSR1): c.2042del (p.Asn681Metfs) deletion Likely pathogenic GRCh37 Chromosome 22, 46931026: 46931026
6 CELSR1 NM_014246.2(CELSR1): c.2042del (p.Asn681Metfs) deletion Likely pathogenic GRCh38 Chromosome 22, 46535129: 46535129
7 CELSR1 NM_014246.1(CELSR1): c.5226+2T> A single nucleotide variant Pathogenic GRCh38 Chromosome 22, 46408994: 46408994
8 CELSR1 NM_014246.1(CELSR1): c.5226+2T> A single nucleotide variant Pathogenic GRCh37 Chromosome 22, 46804891: 46804891
9 CELSR1 NM_014246.1(CELSR1): c.6739+1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 22, 46782298: 46782298
10 CELSR1 NM_014246.1(CELSR1): c.6739+1G> A single nucleotide variant Pathogenic GRCh38 Chromosome 22, 46386401: 46386401

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

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

(show all 30)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.96 CELSR1 FOXC1 FOXC2 FOXL1 VEGFC
2 regulation of transcription, DNA-templated GO:0006355 9.93 FOXC1 FOXC2 FOXL1 SOX18
3 positive regulation of transcription, DNA-templated GO:0045893 9.91 FOXC1 FOXC2 PHF19 SOX18
4 cell differentiation GO:0030154 9.8 FOXC1 FOXC2 FOXL1 SOX18 VEGFC
5 heart development GO:0007507 9.78 FOXC1 FOXC2 FOXL1 SOX18
6 angiogenesis GO:0001525 9.76 FLT4 FOXC1 SOX18 VEGFC
7 anatomical structure morphogenesis GO:0009653 9.7 FOXC1 FOXC2 FOXL1
8 somitogenesis GO:0001756 9.65 FOXC1 FOXC2
9 positive regulation of endothelial cell migration GO:0010595 9.64 FLT4 FOXC2
10 heart morphogenesis GO:0003007 9.64 FOXC1 FOXC2
11 collagen fibril organization GO:0030199 9.63 FOXC1 FOXC2
12 ureteric bud development GO:0001657 9.62 FOXC1 FOXC2
13 hair follicle development GO:0001942 9.62 CELSR1 SOX18
14 blood vessel remodeling GO:0001974 9.61 FOXC1 FOXC2
15 blood vessel development GO:0001568 9.61 FOXC1 FOXC2 SOX18
16 sprouting angiogenesis GO:0002040 9.6 FLT4 VEGFC
17 vasculature development GO:0001944 9.59 FLT4 SOX18
18 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.58 FOXC1 FOXC2
19 artery morphogenesis GO:0048844 9.58 FOXC1 FOXC2
20 neural crest cell development GO:0014032 9.57 FOXC1 FOXC2
21 regulation of blood vessel size GO:0050880 9.55 FOXC1 FOXC2
22 cardiac muscle cell proliferation GO:0060038 9.54 FOXC1 FOXC2
23 regulation of organ growth GO:0046620 9.51 FOXC1 FOXC2
24 embryonic heart tube development GO:0035050 9.5 FOXC1 FOXC2 SOX18
25 paraxial mesoderm formation GO:0048341 9.49 FOXC1 FOXC2
26 vascular endothelial growth factor signaling pathway GO:0038084 9.43 FLT4 FOXC1 VEGFC
27 negative regulation of apoptotic process involved in outflow tract morphogenesis GO:1902257 9.37 FOXC1 FOXC2
28 lymphangiogenesis GO:0001946 9.33 FLT4 FOXC2 SOX18
29 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.26 FLT4 FOXC1 FOXC2 VEGFC
30 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
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