MCID: HRD007
MIFTS: 54

Hereditary Lymphedema malady

Genetic diseases, Rare diseases, Eye diseases, Cardiovascular diseases, Skin diseases, Immune diseases categories

Summaries for Hereditary Lymphedema

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NIH Rare Diseases:43 Milroy disease is a lymphatic disease that causes swelling (lymphedema) in the lower legs and feet. lymphedema is usually present at birth or develops in infancy. it typically occurs on both sides of the body and can worsen over time. other symptoms may include accumulation of fluid in the scrotum in males (hydrocele), upslanting toenails, deep creases in the toes, wart-like growths, prominent leg veins, and/or cellulitis. milroy disease is sometimes caused by changes (mutations) in the flt4 gene and is inherited in an autosomal dominant manner. in many cases, the cause remains unknown. treatment may include lymphedema therapy to improve function and alleviate symptoms. last updated: 1/29/2015

MalaCards based summary: Hereditary Lymphedema, also known as milroy disease, is related to lymphedema and lymphedema-distichiasis syndrome, and has symptoms including wide mouth, full cheeks and micrognathia. An important gene associated with Hereditary Lymphedema is FLT4 (fms-related tyrosine kinase 4), and among its related pathways are Tyrosine Kinases / Adaptors and VEGF Signaling Pathway. Affiliated tissues include legs, eye and skin, and related mouse phenotypes are cardiovascular system and normal.

Disease Ontology:10 A lymphedema commonly located in legs, caused by congenital abnormalities in the lymphatic system.

Genetics Home Reference:23 Milroy disease is a condition that affects the normal function of the lymphatic system. The lymphatic system produces and transports fluids and immune cells throughout the body. Impaired transport with accumulation of lymph fluid can cause swelling (lymphedema). Individuals with Milroy disease typically have lymphedema in their lower legs and feet at birth or develop it in infancy. The lymphedema typically occurs on both sides of the body and may worsen over time.

Wikipedia:65 Milroy\'s disease is a familial disease characterized by lymphedema, commonly in the legs, caused by... more...

GeneReviews summary for milroy

Aliases & Classifications for Hereditary Lymphedema

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Sources:
10Disease Ontology, 43NIH Rare Diseases, 62UMLS, 23Genetics Home Reference, 49Orphanet, 21GeneReviews, 22GeneTests, 24GTR, 29ICD9CM, 28ICD10 via Orphanet, 63UMLS via Orphanet
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Hereditary Lymphedema, Aliases & Descriptions:

Name: Hereditary Lymphedema 10 43 62
Milroy Disease 21 43 22 23 49
Hereditary Lymphedema Type I 23 49 24 62
Nonne-Milroy Lymphedema 10 23 49 62
Milroy's Disease 10 43 23
Congenital Hereditary Lymphedema 43 62
Congenital Familial Lymphedema 23 62
Primary Congenital Lymphedema 43 62
Hereditary Lymphedema 1 43 62
 
Nonne-Milroy Disease 43 62
Hereditary Lymphedema, Type I 21
Congenital Primary Lymphedema 43
Milroy Congenital Lymphedema 21
Lymphedema, Early-Onset 62
Early Onset Lymphedema 43
Nonne-Milroy Syndrome 43
Nonne’s Syndrome 43


Classifications:



Characteristics (Orphanet epidemiological data):

49
milroy disease:
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal


External Ids:

Disease Ontology10 DOID:0050580
ICD9CM29 757.0
Orphanet49 79452
ICD10 via Orphanet28 Q82.0
UMLS via Orphanet63 C1704423

Related Diseases for Hereditary Lymphedema

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



Diseases related to hereditary lymphedema

Symptoms for Hereditary Lymphedema

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HPO human phenotypes related to Hereditary Lymphedema:

(show all 14)
id Description Frequency HPO Source Accession
1 wide mouth hallmark (90%) HP:0000154
2 full cheeks hallmark (90%) HP:0000293
3 micrognathia hallmark (90%) HP:0000347
4 abnormality of the eye hallmark (90%) HP:0000478
5 downslanted palpebral fissures hallmark (90%) HP:0000494
6 lymphedema hallmark (90%) HP:0001004
7 abnormality of the intestine hallmark (90%) HP:0002242
8 erysipelas typical (50%) HP:0001055
9 patent ductus arteriosus typical (50%) HP:0001643
10 abnormality of the aorta typical (50%) HP:0001679
11 short stature typical (50%) HP:0004322
12 cognitive impairment typical (50%) HP:0100543
13 skin ulcer typical (50%) HP:0200042
14 verrucae occasional (7.5%) HP:0200043

Drugs & Therapeutics for Hereditary Lymphedema

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Drug clinical trials:

Search ClinicalTrials for Hereditary Lymphedema

Search NIH Clinical Center for Hereditary Lymphedema

Genetic Tests for Hereditary Lymphedema

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Genetic tests related to Hereditary Lymphedema:

id Genetic test Affiliating Genes
1 Milroy Disease22 FLT4
2 Hereditary Lymphedema Type I24

Anatomical Context for Hereditary Lymphedema

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MalaCards organs/tissues related to Hereditary Lymphedema:

33
Eye, Skin

FMA organs/tissues related to Hereditary Lymphedema:

16
Legs

Animal Models for Hereditary Lymphedema or affiliated genes

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MGI Mouse Phenotypes related to Hereditary Lymphedema:

37
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053858.3FLT4, FOXC2, FOXC1, VEGFC
2MP:00028738.0GJC2, FOXC1, FOXC2, FLT4
3MP:00053818.0FOXL1, FOXC1, FLT4, FOXC2
4MP:00107687.3GJC2, FOXC1, FOXL1, FOXC2, FLT4, VEGFC

Publications for Hereditary Lymphedema

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Articles related to Hereditary Lymphedema:

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

Variations for Hereditary Lymphedema

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Clinvar genetic disease variations for Hereditary Lymphedema:

7 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1FLT4NM_182925.4(FLT4): c.2569G> A (p.Gly857Arg)single nucleotide variantPathogenicrs267606818GRCh37Chr 5, 180046743: 180046743
2FLT4NM_182925.4(FLT4): c.3122G> C (p.Arg1041Pro)single nucleotide variantPathogenicrs121909650GRCh37Chr 5, 180043464: 180043464
3FLT4NM_182925.4(FLT4): c.3131T> C (p.Leu1044Pro)single nucleotide variantPathogenicrs121909651GRCh37Chr 5, 180043455: 180043455
4FLT4NM_182925.4(FLT4): c.3341C> T (p.Pro1114Leu)single nucleotide variantPathogenicrs121909652GRCh37Chr 5, 180040101: 180040101
5FLT4NM_182925.4(FLT4): c.2632G> A (p.Val878Met)single nucleotide variantPathogenicrs121909654GRCh37Chr 5, 180046680: 180046680
6FLT4NM_182925.4(FLT4): c.3257T> C (p.Ile1086Thr)single nucleotide variantPathogenicrs121909655GRCh37Chr 5, 180041142: 180041142
7FLT4NM_182925.4(FLT4): c.3316G> A (p.Glu1106Lys)single nucleotide variantPathogenicrs121909656GRCh37Chr 5, 180041083: 180041083
8FLT4FLT4, 3-BP DEL, 3323TCTdeletionPathogenic
9FLT4NM_182925.4(FLT4): c.2563G> A (p.Ala855Thr)single nucleotide variantPathogenicrs121909657GRCh37Chr 5, 180046749: 180046749
10GJC2NM_020435.3(GJC2): c.143C> T (p.Ser48Leu)single nucleotide variantPathogenicrs267606847GRCh37Chr 1, 228345602: 228345602
11GJC2NM_020435.3(GJC2): c.778C> T (p.Arg260Cys)single nucleotide variantPathogenicrs267606846GRCh37Chr 1, 228346237: 228346237

Expression for genes affiliated with Hereditary Lymphedema

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Search GEO for disease gene expression data for Hereditary Lymphedema.

Pathways for genes affiliated with Hereditary Lymphedema

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Pathways related to Hereditary Lymphedema according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.6VEGFC, FLT4
2
Show member pathways
9.6VEGFC, FLT4
3
Show member pathways
VEGFR1 specific signals38
9.6VEGFC, FLT4
4
Show member pathways
9.6VEGFC, FLT4
5
Show member pathways
9.6FLT4, VEGFC
6
Show member pathways
9.6FLT4, VEGFC
79.6FLT4, VEGFC
88.7VEGFC, FOXC2, FOXC1

Compounds for genes affiliated with Hereditary Lymphedema

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GO Terms for genes affiliated with Hereditary Lymphedema

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Biological processes related to Hereditary Lymphedema according to GeneCards/GeneDecks:

(show all 26)
idNameGO IDScoreTop Affiliating Genes
1lymphangiogenesisGO:00019469.9FLT4, FOXC2
2positive regulation of endothelial cell migrationGO:00105959.8FOXC2, FLT4
3lymph vessel developmentGO:00019459.6FOXC1, FLT4
4negative regulation of apoptotic process involved in outflow tract morphogenesisGO:019022579.5FOXC2, FOXC1
5regulation of organ growthGO:00466209.5FOXC1, FOXC2
6cardiac muscle cell proliferationGO:00600389.5FOXC2, FOXC1
7regulation of blood vessel sizeGO:00508809.5FOXC2, FOXC1
8neural crest cell developmentGO:00140329.4FOXC1, FOXC2
9embryonic heart tube developmentGO:00350509.4FOXC1, FOXC2
10artery morphogenesisGO:00488449.4FOXC1, FOXC2
11ventricular cardiac muscle tissue morphogenesisGO:00550109.4FOXC1, FOXC2
12blood vessel remodelingGO:00019749.4FOXC1, FOXC2
13collagen fibril organizationGO:00301999.4FOXC2, FOXC1
14ureteric bud developmentGO:00016579.3FOXC2, FOXC1
15tissue developmentGO:00098889.3FOXL1, FOXC1
16somitogenesisGO:00017569.3FOXC1, FOXC2
17organ morphogenesisGO:00098879.3FOXL1, VEGFC
18regulation of sequence-specific DNA binding transcription factor activityGO:00510909.3FOXC2, FOXC1
19ossificationGO:00015039.1FOXC2, FOXC1
20Notch signaling pathwayGO:00072199.1FOXC1, FOXC2
21pattern specification processGO:00073899.1FOXC1, FOXL1
22camera-type eye developmentGO:00430108.9FOXC1, FOXL1, FOXC2
23negative regulation of apoptotic processGO:00430668.9FOXC1, FOXC2, FLT4
24heart developmentGO:00075078.8FOXC1, FOXL1, FOXC2
25embryo developmentGO:00097908.7FOXC1, FOXL1
26vascular endothelial growth factor receptor signaling pathwayGO:00480108.7FOXC1, FOXC2, FLT4, VEGFC

Molecular functions related to Hereditary Lymphedema according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1chromatin DNA bindingGO:00314909.1FOXC1, FOXC2
2double-stranded DNA bindingGO:00036909.1FOXC1, FOXC2
3RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activityGO:00037058.8FOXC1, FOXC2
4DNA binding, bendingGO:00083018.6FOXC1, FOXL1, FOXC2
5sequence-specific DNA bindingGO:00435658.4FOXC2, FOXL1, FOXC1

Products for genes affiliated with Hereditary Lymphedema

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Sources for Hereditary Lymphedema

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4CDC
15ExPASy
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
52PubMed
53QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet