MCID: HRD007
MIFTS: 41

Hereditary Lymphedema

Categories: Rare diseases, Immune diseases, Genetic diseases

Aliases & Classifications for Hereditary Lymphedema

MalaCards integrated aliases for Hereditary Lymphedema:

Name: Hereditary Lymphedema 12 50 14
Milroy Disease 23 50 24 25 69
Hereditary Lymphedema Type I 50 25 29
Nonne-Milroy Lymphedema 12 50 25
Milroy's Disease 12 50 25
Hereditary Lymphedema, Type I 23 24
Milroy Congenital Lymphedema 23 24
Congenital Hereditary Lymphedema 50
Hereditary Lymphoedema, Type I 24
Congenital Familial Lymphedema 25
Congenital Primary Lymphedema 50
Primary Congenital Lymphedema 50
Milroy Congenital Lymphoedema 24
Lymphedema, Hereditary I 13
Hereditary Lymphedema 1 50
Early Onset Lymphedema 50
Nonne-Milroy Syndrome 50
Nonne-Milroy Disease 50
Nonne’s Syndrome 50

Characteristics:

GeneReviews:

23
Penetrance Approximately 85%-90% of individuals who have a pathogenic variant in flt4 develop lower-limb lymphedema by age three years; conversely, 10%-15% of individuals with an flt4 pathogenic variant are clinically unaffected. ...

Classifications:



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Disease Ontology 12 DOID:0050580
ICD9CM 35 757.0
UMLS 69 C1313885

Summaries for Hereditary Lymphedema

NIH Rare Diseases : 50 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 hereditary lymphedema type ii and lymphedema, hereditary, ic. An important gene associated with Hereditary Lymphedema is FLT4 (Fms Related Tyrosine Kinase 4), and among its related pathways/superpathways is Heart Development. The drugs Paroxetine and Antidepressive Agents have been mentioned in the context of this disorder. Affiliated tissues include breast, and related phenotype is digestive/alimentary.

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

Wikipedia : 72 Milroy\'s disease (MD) is a familial disease characterized by lymphedema, commonly in the legs, caused... more...

GeneReviews: NBK1239

Related Diseases for Hereditary Lymphedema

Diseases in the Lymphedema family:

Lymphedema, Hereditary, Ic Lymphedema, Hereditary, Id
Lymphedema, Hereditary, Ia Lymphedema, Hereditary, Ib
Lymphedema, Hereditary, Iii Hereditary Lymphedema
Congenital Lymphedema Hereditary Lymphedema Type Ii

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

(show all 29)
id Related Disease Score Top Affiliating Genes
1 hereditary lymphedema type ii 12.2
2 lymphedema, hereditary, ic 11.4
3 lymphedema, hereditary, ia 11.3
4 lymphedema-distichiasis syndrome 11.2
5 lymphedema, hereditary, id 10.8
6 lymphedema, hereditary, iii 10.8
7 lymphedema 10.4
8 trigonocephaly with short stature and developmental delay 10.0 FLT4 FOXC2
9 renal adenoma 10.0 FLT4 GJC2
10 distichiasis 9.9
11 miyoshi muscular dystrophy 2 9.9 FLT4 FOXC2
12 lymphangiosarcoma 9.8
13 congenital mitral stenosis 9.7 FLT4 FOXC2 HNRNPH1
14 mucopolysaccharidosis iva 9.7 FOXC2 FOXL1
15 cholestasis 9.6
16 obstructive jaundice 9.6
17 elephantiasis 9.6
18 hemangioendothelioma 9.6
19 hydrops fetalis 9.6
20 kaposiform hemangioendothelioma 9.6
21 glaucoma 3, primary congenital, e 9.6 FLT4 FOXC2
22 pediatric supratentorial ependymoma 9.6 FLT4 FOXC2 GJC2
23 ichthyosis lamellar 2 9.5 FOXC2 FOXL1
24 sleep apnea 9.4 FOXC1 FOXC2 GJC2
25 tuberculosis 9.4 FOXC1 FOXC2 GJC2
26 angioosteohypertrophic syndrome 9.3 FOXC1 FOXL1
27 lymphoid leukemia 9.2 FLT4 FOXC2 GJC2 HNRNPH1
28 handigodu joint disease 9.1 FOXC1 FOXC2 FOXL1
29 gummatous syphilis 7.8 FLT4 FOXC1 FOXC2 FOXL1 GJC2 HNRNPH1

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:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 8.92 FLT4 FOXC1 FOXC2 FOXL1

Drugs & Therapeutics for Hereditary Lymphedema

Drugs for Hereditary Lymphedema (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 20)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Paroxetine Approved, Investigational Phase 3 61869-08-7 43815
2 Antidepressive Agents Phase 3
3 Antidepressive Agents, Second-Generation Phase 3
4 Cytochrome P-450 CYP2D6 Inhibitors Phase 3
5 Cytochrome P-450 Enzyme Inhibitors Phase 3
6 Neurotransmitter Agents Phase 3,Phase 2
7 Neurotransmitter Uptake Inhibitors Phase 3
8 Psychotropic Drugs Phase 3
9
Serotonin Phase 3 50-67-9 5202
10 Serotonin Agents Phase 3
11 Serotonin Uptake Inhibitors Phase 3
12
Propranolol Approved, Investigational Phase 2 525-66-6 4946
13 Adrenergic Agents Phase 2
14 Adrenergic Antagonists Phase 2
15 Adrenergic beta-Antagonists Phase 2
16 Anti-Arrhythmia Agents Phase 2
17 Antihypertensive Agents Phase 2
18 Vasodilator Agents Phase 2
19
Ethanol Approved 64-17-5 702
20 Complement System Proteins

Interventional clinical trials:

(show all 12)

id 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 Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment Unknown status NCT01273909
4 Validation of a New Method of Limb Volumetry Unknown status NCT01574911
5 Physical Therapies in the Decongestive Treatment of Lymphedema Completed NCT01748604
6 Out-of Pocket Payments in Patients With Lymphedema Recruiting NCT02988479
7 Out-of Pocket Payments With Lymphedema in France Recruiting NCT02988505
8 Validation of Metrological Properties of Lymphoqol Recruiting NCT01922635
9 Engineering an Online STI Prevention Program Recruiting NCT02897804
10 Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced PCD Recruiting NCT02661646
11 Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders Enrolling by invitation NCT00833599 NIRFLI with ICG
12 Oedema Study : Chroedem Not yet recruiting NCT02914808

Search NIH Clinical Center for Hereditary Lymphedema

Genetic Tests for Hereditary Lymphedema

Genetic tests related to Hereditary Lymphedema:

id Genetic test Affiliating Genes
1 Hereditary Lymphedema Type I 29

Anatomical Context for Hereditary Lymphedema

MalaCards organs/tissues related to Hereditary Lymphedema:

39
Breast

Publications for Hereditary Lymphedema

Articles related to Hereditary Lymphedema:

(show all 35)
id Title Authors Year
1
Hereditary Lymphedema of the Leg - A Case Report. ( 28785330 )
2017
2
A novel mutation in CELSR1 is associated with hereditary lymphedema. ( 26855770 )
2016
3
Antenatal presentation of hereditary lymphedema type I. ( 25896638 )
2015
4
A Novel Missense Mutation in FLT4 Causes Autosomal Recessive Hereditary Lymphedema. ( 26091405 )
2015
5
Hereditary Lymphedema, Characteristics, and Variations in 17 Adult Patients with Lymphedema Cholestasis Syndrome 1/Aagenaes Syndrome. ( 25317502 )
2014
6
Excision of Elephantiasis Nostras Verrucosa Lesions in a Patient With Hereditary Lymphedema: Case Report and Review of the Literature. ( 25441846 )
2014
7
Hydrops fetalis and pulmonary lymphangiectasia due to FOXC2 mutation: an autosomal dominant hereditary lymphedema syndrome with variable expression. ( 21918810 )
2012
8
Identification of a novel VEGFR-3 missense mutation in a Chinese family with hereditary lymphedema type I. ( 17945164 )
2007
9
Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3. ( 16924388 )
2006
10
Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations. ( 16965327 )
2006
11
Clinical variability in a Japanese hereditary lymphedema type I family with an FLT4 mutation. ( 15904433 )
2005
12
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
13
Stewart-Treves syndrome as a rare complication of a hereditary lymphedema. ( 15061047 )
2004
14
A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus. ( 15523639 )
2004
15
Age of onset in hereditary lymphedema. ( 12838201 )
2003
16
Kaposiform hemangioendothelioma associated with Milroy's disease (primary hereditary lymphedema). ( 12861592 )
2003
17
Syndromic classification of hereditary lymphedema. ( 14992570 )
2003
18
A model for gene therapy of human hereditary lymphedema. ( 11592985 )
2001
19
Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. ( 11078474 )
2000
20
Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. ( 10856194 )
2000
21
Lymphangiosarcoma of the pubic region: a rare complication arising in congenital non-hereditary lymphedema. ( 9854166 )
1998
22
Hereditary lymphedema: evidence for linkage and genetic heterogeneity. ( 9817924 )
1998
23
Lymphangiosarcoma in late-onset hereditary lymphedema: case report and nosological implications. ( 7747790 )
1995
24
Hereditary lymphedema and distichiasis. ( 2064580 )
1991
25
Hereditary lymphedema in Hereford cattle. ( 2039787 )
1991
26
Congenital hereditary lymphedema (Nonne/Milroy). ( 2616174 )
1989
27
The pathogenesis of congenital hereditary lymphedema in the pig. ( 642583 )
1978
28
Scintilymphangiography with 99 mTc-antimony sulfide colloid in hereditary lymphedema (Nonne-Milroy diseases). ( 709985 )
1978
29
Congenital hereditary lymphedema in the pig. ( 642582 )
1978
30
Chronic hereditary lymphedema of the legs with congenital conjunctival lymphedema. ( 5020171 )
1972
31
Hereditary lymphedema and obstructive jaundice. ( 5544157 )
1971
32
PLEURAL EFFUSION IN CHRONIC HEREDITARY LYMPHEDEMA (NONNE, MILROY, MEIGE'S DISEASE). REPORT OF TWO CASES. ( 14115303 )
1964
33
Genetic and physiological aspects of a family with chronic hereditary lymphedema (Nonne-Milroy-Meige's disease) and hereditary angioneurotic edema. ( 13533392 )
1958
34
Prednisone in the management of idiopathic hereditary lymphedema (Milroy's disease). ( 13345610 )
1956
35
Chronic hereditary lymphedema (Nonne-Milroy-Meige's Disease). ( 15418956 )
1950

Variations for Hereditary Lymphedema

ClinVar genetic disease variations for Hereditary Lymphedema:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 FLT4 NM_182925.4(FLT4): c.2569G> A (p.Gly857Arg) single nucleotide variant Pathogenic rs267606818 GRCh37 Chromosome 5, 180046743: 180046743
2 FLT4 NM_182925.4(FLT4): c.3122G> C (p.Arg1041Pro) single nucleotide variant Pathogenic rs121909650 GRCh37 Chromosome 5, 180043464: 180043464
3 FLT4 NM_182925.4(FLT4): c.3131T> C (p.Leu1044Pro) single nucleotide variant Pathogenic rs121909651 GRCh37 Chromosome 5, 180043455: 180043455
4 FLT4 NM_182925.4(FLT4): c.3341C> T (p.Pro1114Leu) single nucleotide variant Pathogenic rs121909652 GRCh37 Chromosome 5, 180040101: 180040101
5 FLT4 NM_182925.4(FLT4): c.3104A> G (p.His1035Arg) single nucleotide variant Pathogenic rs121909653 GRCh37 Chromosome 5, 180043482: 180043482
6 FLT4 NM_182925.4(FLT4): c.2632G> A (p.Val878Met) single nucleotide variant Pathogenic rs121909654 GRCh37 Chromosome 5, 180046680: 180046680
7 FLT4 NM_182925.4(FLT4): c.3257T> C (p.Ile1086Thr) single nucleotide variant Pathogenic rs121909655 GRCh37 Chromosome 5, 180041142: 180041142
8 FLT4 NM_182925.4(FLT4): c.3316G> A (p.Glu1106Lys) single nucleotide variant Pathogenic rs121909656 GRCh37 Chromosome 5, 180041083: 180041083
9 FLT4 NM_182925.4(FLT4): c.3323_3325delTCT (p.Phe1108del) deletion Pathogenic rs587776833 GRCh38 Chromosome 5, 180614074: 180614076
10 FLT4 NM_182925.4(FLT4): c.2563G> A (p.Ala855Thr) single nucleotide variant Pathogenic rs121909657 GRCh37 Chromosome 5, 180046749: 180046749

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 GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 10.29 FOXC1 FOXC2

GO Terms for Hereditary Lymphedema

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

(show all 25)
id Name GO ID Score Top Affiliating Genes
1 heart development GO:0007507 9.71 FOXC1 FOXC2 FOXL1
2 Notch signaling pathway GO:0007219 9.62 FOXC1 FOXC2
3 kidney development GO:0001822 9.62 FOXC1 FOXC2
4 ossification GO:0001503 9.61 FOXC1 FOXC2
5 camera-type eye development GO:0043010 9.61 FOXC1 FOXC2
6 blood vessel development GO:0001568 9.6 FOXC1 FOXC2
7 heart morphogenesis GO:0003007 9.59 FOXC1 FOXC2
8 somitogenesis GO:0001756 9.58 FOXC1 FOXC2
9 positive regulation of endothelial cell migration GO:0010595 9.58 FLT4 FOXC2
10 ureteric bud development GO:0001657 9.57 FOXC1 FOXC2
11 collagen fibril organization GO:0030199 9.56 FOXC1 FOXC2
12 blood vessel remodeling GO:0001974 9.55 FOXC1 FOXC2
13 ventricular cardiac muscle tissue morphogenesis GO:0055010 9.52 FOXC1 FOXC2
14 artery morphogenesis GO:0048844 9.51 FOXC1 FOXC2
15 neural crest cell development GO:0014032 9.49 FOXC1 FOXC2
16 embryonic heart tube development GO:0035050 9.48 FOXC1 FOXC2
17 regulation of blood vessel size GO:0050880 9.46 FOXC1 FOXC2
18 cardiac muscle cell proliferation GO:0060038 9.43 FOXC1 FOXC2
19 lymphangiogenesis GO:0001946 9.4 FLT4 FOXC2
20 regulation of organ growth GO:0046620 9.37 FOXC1 FOXC2
21 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.33 FLT4 FOXC1 FOXC2
22 paraxial mesoderm formation GO:0048341 9.32 FOXC1 FOXC2
23 vascular endothelial growth factor signaling pathway GO:0038084 9.26 FLT4 FOXC1
24 negative regulation of apoptotic process involved in outflow tract morphogenesis GO:1902257 8.96 FOXC1 FOXC2
25 lymph vessel development GO:0001945 8.8 FLT4 FOXC1 FOXC2

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

id Name GO ID Score Top Affiliating Genes
1 sequence-specific DNA binding GO:0043565 9.43 FOXC1 FOXC2 FOXL1
2 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0003705 9.16 FOXC1 FOXC2
3 promoter-specific chromatin binding GO:1990841 8.96 FOXC1 FOXC2
4 DNA binding, bending GO:0008301 8.62 FOXC1 FOXL1

Sources for Hereditary Lymphedema

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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