MCID: HRD007
MIFTS: 57

Hereditary Lymphedema malady

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

Summaries for Hereditary Lymphedema

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44NIH Rare Diseases, 22Genetics Home Reference, 66Wikipedia, 48OMIM, 20GeneReviews, 34MalaCards
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NIH Rare Diseases:44 Milroy disease is a lymphatic disease that causes swelling (lymphedema) in the lower legs and feet soon after birth. other symptoms may include accumulation of fluid in the scrotum, abnormalities of the urethra, upslanting toenails, deep creases in the toes, wart-like growths, prominent leg veins, and cellulitis. gene mutations in the flt4 gene cause some cases of milroy disease, however for many cases the cause of the disorder is unknown. last updated: 7/29/2011

MalaCards: Hereditary Lymphedema, also known as milroy disease, is related to lymphedema and lymphedema-distichiasis syndrome, and has symptoms including patent ductus arteriosus, intellectual deficit/mental/psychomotor retardation/learning disability and short stature/dwarfism/nanism. 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 skin, eye and colon, and related mouse phenotypes are cardiovascular system and digestive/alimentary.

Genetics Home Reference:22 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:66 Milroy\'s disease is a familial disease characterized by lymphedema, commonly in the legs, caused by... more...

Description from OMIM:48 153100,613480,615907,247440,611944

GeneReviews summary for milroy

Aliases & Classifications for Hereditary Lymphedema

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9Disease Ontology, 20GeneReviews, 44NIH Rare Diseases, 21GeneTests, 23GTR, 22Genetics Home Reference, 48OMIM, 50Orphanet, 63UMLS, 60SNOMED-CT via Orphanet, 27ICD10 via Orphanet, 64UMLS via Orphanet
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Classifications:



Characteristics (Orphanet epidemiological data):

50
congenital primary lymphedema:
Inheritance: Autosomal dominant,Sporadic; Prevalence: 1-9/100000; Age of onset: Neonatal/infancy
milroy disease:
Inheritance: Autosomal dominant; Age of onset: Neonatal/infancy


Aliases & Descriptions:

hereditary lymphedema 9 44 63
milroy disease 20 44 21 22 50 48
nonne-milroy lymphedema 9 22 50
milroy's disease 9 44 22
hereditary lymphedema type i 22 50
hereditary lymphedema 1 44 23
congenital hereditary lymphedema 44
congenital familial lymphedema 22
hereditary lymphedema, type i 20
primary congenital lymphedema 44
congenital primary lymphedema 50
milroy congenital lymphedema 20
lymphedema, hereditary i 48
early onset lymphedema 44
nonne-milroy syndrome 44
nonne-milroy disease 44
nonne’s syndrome 44


External Ids:

Disease Ontology9 DOID:0050580
SNOMED-CT via Orphanet60 399889006
ICD10 via Orphanet27 Q82.0
UMLS via Orphanet64 C1704423

Related Diseases for Hereditary Lymphedema

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18GeneCards, 19GeneDecks
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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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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

153100

Clinical features from OMIM:

153100,613480,615907,247440,611944

Symptoms:

50 (show all 19)
  • patent ductus arteriosus
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • short stature/dwarfism/nanism
  • warts/papillomas
  • autosomal recessive inheritance
  • x-linked recessive inheritance
  • asthenia/fatigue/weakness
  • hypoplastic aorta/coarctation/stenosis/anomaly/aortic arch interruption
  • erysipela
  • downslanted palpebral fissures/anti-mongoloid slanting palpebral fissures
  • micrognathia/retrognathia/micrognathism/retrognathism
  • anomalies of eyes and vision
  • anomalies of eyelids, eyelashes and lacrimal system
  • macrostomia/big mouth
  • intestinal/colonic anomaly
  • lymphedema
  • metabolic anomalies
  • chronic skin infection/ulcerations/ulcers/cancrum
  • broad cheeks/cherub-like/cherubin face

Drugs & Therapeutics for Hereditary Lymphedema

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6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials
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Approved drugs:

Search CenterWatch for Hereditary Lymphedema

Drug clinical trials:

Search ClinicalTrials for Hereditary Lymphedema

Search NIH Clinical Center for Hereditary Lymphedema

Search CenterWatch for Hereditary Lymphedema

Genetic Tests for Hereditary Lymphedema

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21GeneTests, 23GTR
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Genetic tests related to Hereditary Lymphedema:

id Genetic test Affiliating Genes
1 Milroy Disease21 FLT4
2 Hereditary Lymphedema Type I23

Anatomical Context for Hereditary Lymphedema

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34MalaCards
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MalaCards organs/tissues related to Hereditary Lymphedema:

34
Skin, Eye, Colon

Animal Models for Hereditary Lymphedema or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Hereditary Lymphedema:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053858.3FOXC1, FOXC2, FLT4, VEGFC
2MP:00053818.0FLT4, FOXC2, FOXL1, FOXC1
3MP:00028738.0FLT4, FOXC2, FOXC1, GJC2
4MP:00107687.3GJC2, FOXC1, FOXL1, FOXC2, FLT4, VEGFC

Publications for Hereditary Lymphedema

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53PubMed
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Articles related to Hereditary Lymphedema:

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

Variations for Hereditary Lymphedema

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Hereditary Lymphedema:

65
id Symbol AA change Variation ID SNP ID
1FLT4p.Gly857ArgVAR_018409
2FLT4p.His1035ArgVAR_018412
3FLT4p.Arg1041ProVAR_018413
4FLT4p.Leu1044ProVAR_018414
5FLT4p.Pro1114LeuVAR_018415

Clinvar genetic disease variations for Hereditary Lymphedema:

1
id Gene Name 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

Expression for genes affiliated with Hereditary Lymphedema

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Hereditary Lymphedema

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Pathways for genes affiliated with Hereditary Lymphedema

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51PathCards, 5Cell Signaling Technology, 52PharmGKB, 58SinoBiological, 39NCBI BioSystems Database, 56Reactome, 62Tocris Bioscience, 54QIAGEN, 61Thomson Reuters
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Pathways related to Hereditary Lymphedema according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.7VEGFC, FLT4
2
Show member pathways
9.7VEGFC, FLT4
3
Show member pathways
VEGFR1 specific signals39
9.7VEGFC, FLT4
4
Show member pathways
9.7VEGFC, FLT4
5
Show member pathways
9.7FLT4, VEGFC
6
Show member pathways
9.7FLT4, VEGFC
79.7FLT4, 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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17Gene Ontology
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Biological processes related to Hereditary Lymphedema according to GeneCards/GeneDecks:

(show all 26)
idNameGO IDScoreTop Affiliating Genes
1lymphangiogenesisGO:0019469.9FLT4, FOXC2
2positive regulation of endothelial cell migrationGO:0105959.8FOXC2, FLT4
3lymph vessel developmentGO:0019459.6FOXC1, FLT4
4negative regulation of apoptotic process involved in outflow tract morphogenesisGO:19022579.5FOXC2, FOXC1
5regulation of organ growthGO:0466209.5FOXC1, FOXC2
6cardiac muscle cell proliferationGO:0600389.5FOXC2, FOXC1
7regulation of blood vessel sizeGO:0508809.5FOXC2, FOXC1
8neural crest cell developmentGO:0140329.4FOXC1, FOXC2
9embryonic heart tube developmentGO:0350509.4FOXC1, FOXC2
10artery morphogenesisGO:0488449.4FOXC1, FOXC2
11ventricular cardiac muscle tissue morphogenesisGO:0550109.4FOXC1, FOXC2
12blood vessel remodelingGO:0019749.4FOXC1, FOXC2
13collagen fibril organizationGO:0301999.4FOXC2, FOXC1
14organ morphogenesisGO:0098879.3FOXL1, VEGFC
15ureteric bud developmentGO:0016579.3FOXC2, FOXC1
16tissue developmentGO:0098889.3FOXL1, FOXC1
17somitogenesisGO:0017569.3FOXC1, FOXC2
18regulation of sequence-specific DNA binding transcription factor activityGO:0510909.3FOXC2, FOXC1
19ossificationGO:0015039.1FOXC2, FOXC1
20Notch signaling pathwayGO:0072199.1FOXC1, FOXC2
21pattern specification processGO:0073899.1FOXC1, FOXL1
22camera-type eye developmentGO:0430108.9FOXC1, FOXL1, FOXC2
23negative regulation of apoptotic processGO:0430668.9FOXC1, FOXC2, FLT4
24heart developmentGO:0075078.8FOXC1, FOXL1, FOXC2
25embryo developmentGO:0097908.7FOXC1, FOXL1
26vascular endothelial growth factor receptor signaling pathwayGO:0480108.7FOXC1, FOXC2, FLT4, VEGFC

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

idNameGO IDScoreTop Affiliating Genes
1chromatin DNA bindingGO:0314909.1FOXC2, FOXC1
2double-stranded DNA bindingGO:0036909.1FOXC2, FOXC1
3RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activityGO:0037058.8FOXC2, FOXC1
4DNA binding, bendingGO:0083018.6FOXC2, FOXC1, FOXL1
5sequence-specific DNA bindingGO:0435658.4FOXL1, FOXC1, FOXC2

Products for genes affiliated with Hereditary Lymphedema

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  • Antibodies
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  • Antibodies

Sources for Hereditary Lymphedema

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4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet