MCID: LYM110
MIFTS: 38

Lymphedema, Hereditary, Ia

Categories: Genetic diseases, Rare diseases, Immune diseases, Neuronal diseases, Reproductive diseases, Muscle diseases, Oral diseases, Cardiovascular diseases

Aliases & Classifications for Lymphedema, Hereditary, Ia

MalaCards integrated aliases for Lymphedema, Hereditary, Ia:

Name: Lymphedema, Hereditary, Ia 57
Milroy Disease 57 24 53 25 75 73
Hereditary Lymphedema Type I 53 25 29 6
Nonne-Milroy Lymphedema 57 53 25 75
Primary Congenital Lymphedema 57 53 75
Milroy's Disease 53 25
Lmph1a 57 75
Pcl 57 75
Primary Congenital Lymphedema; Pcl 57
Congenital Hereditary Lymphedema 53
Lymphedema, Hereditary, Type Ia 40
Congenital Familial Lymphedema 25
Hereditary Lymphedema, Type I 24
Congenital Primary Lymphedema 53
Lymphedema Hereditary Type Ia 75
Milroy Congenital Lymphedema 24
Lymphedema, Hereditary, 1a 75
Lymphedema, Hereditary I 13
Lymphedema, Early-Onset 57
Hereditary Lymphedema 1 53
Early Onset Lymphedema 53
Lymphedema Early-Onset 75
Hereditary Lymphedema 53
Nonne-Milroy Syndrome 53
Nonne-Milroy Disease 53
Nonne’s Syndrome 53

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset usually at birth
later onset may occur
variable expression and severity
more prevalent in females
spontaneous resorption (rare)
lymphedema that presents at puberty is called meige disease


HPO:

32
lymphedema, hereditary, ia:
Onset and clinical course congenital onset
Inheritance autosomal dominant inheritance


GeneReviews:

24
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:



Summaries for Lymphedema, Hereditary, Ia

NIH Rare Diseases : 53 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.

MalaCards based summary : Lymphedema, Hereditary, Ia, also known as milroy disease, is related to plasma cell leukemia and hereditary lymphedema. An important gene associated with Lymphedema, Hereditary, Ia is FLT4 (Fms Related Tyrosine Kinase 4). The drugs Paroxetine and Antidepressive Agents have been mentioned in the context of this disorder. Affiliated tissues include skin and testis, and related phenotypes are abnormality of the nail and hemangioma

Genetics Home Reference : 25 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.

OMIM : 57 Hereditary primary lymphedema is caused by anatomic or functional defects in the lymphatic system, resulting in chronic swelling of body parts. There may be accompanying nail and skin changes, such as nail dysplasia or papillomatosis. Onset is usually at birth or in early childhood but can occur later, and the severity is variable (summary by Gordon et al., 2013 and Balboa-Beltran et al., 2014). (153100)

UniProtKB/Swiss-Prot : 75 Lymphedema, hereditary, 1A: A chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment.

GeneReviews: NBK1239

Related Diseases for Lymphedema, Hereditary, Ia

Diseases in the Lymphedema family:

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

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

(show all 18)
# Related Disease Score Top Affiliating Genes
1 plasma cell leukemia 12.0
2 hereditary lymphedema 11.4
3 lymphedema, hereditary, ic 11.0
4 lymphedema 10.2
5 prostate cancer 9.9
6 prostatitis 9.9
7 personality disorder 9.9
8 colorectal cancer 9.8
9 lung cancer 9.8
10 gastric cancer 9.8
11 leukemia 9.8
12 mastoiditis 9.8
13 antisocial personality disorder 9.8
14 neuroendocrine tumor 9.8
15 post-traumatic stress disorder 9.8
16 trochlear dysplasia 9.8
17 endotheliitis 9.8
18 osteoporotic fracture 9.8

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



Diseases related to Lymphedema, Hereditary, Ia

Symptoms & Phenotypes for Lymphedema, Hereditary, Ia

Symptoms via clinical synopsis from OMIM:

57
Cardiovascular Vascular:
hemangioma

Genitourinary External Genitalia Male:
hydrocele

Muscle Soft Tissue:
lymphedema, predominantly in the lower limbs
lymphography shows hypoplasia of lymphatic vessels

Skin Nails Hair Skin:
hemangioma
hyperkeratosis over edematous areas
papillomatosis over edematous areas

Skin Nails Hair Nails:
upturned toenails

Prenatal Manifestations Amniotic Fluid:
non-immune fetal hydrops (rare)


Clinical features from OMIM:

153100

Human phenotypes related to Lymphedema, Hereditary, Ia:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 abnormality of the nail 32 HP:0001597
2 hemangioma 32 HP:0001028
3 hydrocele testis 32 HP:0000034
4 predominantly lower limb lymphedema 32 HP:0003550
5 hypoplasia of lymphatic vessels 32 HP:0003759
6 nonimmune hydrops fetalis 32 HP:0001790
7 abnormality of the amniotic fluid 32 HP:0001560
8 hyperkeratosis over edematous areas 32 HP:0007448

Drugs & Therapeutics for Lymphedema, Hereditary, Ia

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

(show all 23)
# 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 Agents Phase 3
10 Serotonin Uptake Inhibitors 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 Agents Phase 2
15 Adrenergic Antagonists Phase 2
16 Adrenergic beta-Antagonists Phase 2
17 Anti-Arrhythmia Agents Phase 2
18 Antihypertensive Agents Phase 2
19 Vasodilator Agents Phase 2
20 Adjuvants, Immunologic Phase 2
21 Interferon Inducers Phase 2
22 interferons Phase 2
23 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 Out-of Pocket Payments in Patients With Lymphedema Unknown status NCT02988479
5 Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment Unknown status NCT01273909
6 Validation of a New Method of Limb Volumetry Unknown status NCT01574911
7 Physical Therapies in the Decongestive Treatment of Lymphedema Completed NCT01748604 Not Applicable
8 Out-of Pocket Payments With Lymphedema in France Recruiting NCT02988505
9 Validation of Metrological Properties of Lymphoqol Recruiting NCT01922635 Not Applicable
10 Histologic Analysis of the Lymphatic Vessels Used for Supermicrosurgical Lymphatico-venous Anastomoses in Lymphedema Recruiting NCT03465930
11 A Pilot Study to Evaluate the Feasibility and Potential Effectiveness of the Flexitouch System Head and Neck Treatment Recruiting NCT03332160 Not Applicable
12 Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced PCD Recruiting NCT02661646
13 Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders Enrolling by invitation NCT00833599 NIRFLI with ICG
14 Oedema Study : Chroedem Not yet recruiting NCT02914808

Search NIH Clinical Center for Lymphedema, Hereditary, Ia

Genetic Tests for Lymphedema, Hereditary, Ia

Genetic tests related to Lymphedema, Hereditary, Ia:

# Genetic test Affiliating Genes
1 Hereditary Lymphedema Type I 29 FLT4

Anatomical Context for Lymphedema, Hereditary, Ia

MalaCards organs/tissues related to Lymphedema, Hereditary, Ia:

41
Skin, Testis

Publications for Lymphedema, Hereditary, Ia

Articles related to Lymphedema, Hereditary, Ia:

(show all 11)
# Title Authors Year
1
Atypical retiform hemangioendothelioma arising in a patient with Milroy disease: a case report and review of the literature. ( 27730656 )
2017
2
Milroy Disease or Primary Congenital Lymphedema Associated With Invasive Squamous Cell Carcinoma. ( 27374380 )
2016
3
A NOVEL FLT4 GENE MUTATION AND MR LYMPHANGIOGRAPHY IN A CHINESE FAMILY WITH MILROY DISEASE. ( 26714373 )
2015
4
A novel FLT4 mutation identified in a patient with Milroy disease. ( 25109169 )
2014
5
Four generations of rare familial lymphedema (Milroy disease). ( 23751338 )
2013
6
FLT4/VEGFR3 and Milroy disease: novel mutations, a review of published variants and database update. ( 23074044 )
2013
7
Analysis of the coding regions of VEGFR3 and VEGFC in Milroy disease and other primary lymphoedemas. ( 19002718 )
2009
8
A novel VEGFR3 mutation causes Milroy disease. ( 17458866 )
2007
9
Milroy disease and the VEGFR-3 mutation phenotype. ( 15689446 )
2005
10
Milroy Disease ( 20301417 )
1993
11
Scintilymphangiography with 99 mTc-antimony sulfide colloid in hereditary lymphedema (Nonne-Milroy diseases). ( 709985 )
1978

Variations for Lymphedema, Hereditary, Ia

UniProtKB/Swiss-Prot genetic disease variations for Lymphedema, Hereditary, Ia:

75 (show all 11)
# Symbol AA change Variation ID SNP ID
1 FLT4 p.Gly857Arg VAR_018409 rs267606818
2 FLT4 p.His1035Arg VAR_018412 rs121909653
3 FLT4 p.Arg1041Pro VAR_018413 rs121909650
4 FLT4 p.Leu1044Pro VAR_018414 rs121909651
5 FLT4 p.Pro1114Leu VAR_018415 rs121909652
6 FLT4 p.Ala855Thr VAR_074044 rs121909657
7 FLT4 p.Val878Met VAR_074045 rs121909654
8 FLT4 p.Gln1020Leu VAR_074046
9 FLT4 p.Ile1086Thr VAR_074048 rs121909655
10 FLT4 p.Glu1106Lys VAR_074049 rs121909656
11 FLT4 p.Ser1235Cys VAR_074051

ClinVar genetic disease variations for Lymphedema, Hereditary, Ia:

6
(show all 20)
# 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.2569G> A (p.Gly857Arg) single nucleotide variant Pathogenic rs267606818 GRCh38 Chromosome 5, 180619743: 180619743
3 FLT4 NM_182925.4(FLT4): c.3122G> C (p.Arg1041Pro) single nucleotide variant Pathogenic rs121909650 GRCh37 Chromosome 5, 180043464: 180043464
4 FLT4 NM_182925.4(FLT4): c.3122G> C (p.Arg1041Pro) single nucleotide variant Pathogenic rs121909650 GRCh38 Chromosome 5, 180616464: 180616464
5 FLT4 NM_182925.4(FLT4): c.3131T> C (p.Leu1044Pro) single nucleotide variant Pathogenic rs121909651 GRCh37 Chromosome 5, 180043455: 180043455
6 FLT4 NM_182925.4(FLT4): c.3131T> C (p.Leu1044Pro) single nucleotide variant Pathogenic rs121909651 GRCh38 Chromosome 5, 180616455: 180616455
7 FLT4 NM_182925.4(FLT4): c.3341C> T (p.Pro1114Leu) single nucleotide variant Pathogenic rs121909652 GRCh37 Chromosome 5, 180040101: 180040101
8 FLT4 NM_182925.4(FLT4): c.3341C> T (p.Pro1114Leu) single nucleotide variant Pathogenic rs121909652 GRCh38 Chromosome 5, 180613101: 180613101
9 FLT4 NM_182925.4(FLT4): c.3104A> G (p.His1035Arg) single nucleotide variant Pathogenic rs121909653 GRCh37 Chromosome 5, 180043482: 180043482
10 FLT4 NM_182925.4(FLT4): c.3104A> G (p.His1035Arg) single nucleotide variant Pathogenic rs121909653 GRCh38 Chromosome 5, 180616482: 180616482
11 FLT4 NM_182925.4(FLT4): c.2632G> A (p.Val878Met) single nucleotide variant Pathogenic rs121909654 GRCh37 Chromosome 5, 180046680: 180046680
12 FLT4 NM_182925.4(FLT4): c.2632G> A (p.Val878Met) single nucleotide variant Pathogenic rs121909654 GRCh38 Chromosome 5, 180619680: 180619680
13 FLT4 NM_182925.4(FLT4): c.3257T> C (p.Ile1086Thr) single nucleotide variant Pathogenic rs121909655 GRCh37 Chromosome 5, 180041142: 180041142
14 FLT4 NM_182925.4(FLT4): c.3257T> C (p.Ile1086Thr) single nucleotide variant Pathogenic rs121909655 GRCh38 Chromosome 5, 180614142: 180614142
15 FLT4 NM_182925.4(FLT4): c.3316G> A (p.Glu1106Lys) single nucleotide variant Pathogenic rs121909656 GRCh37 Chromosome 5, 180041083: 180041083
16 FLT4 NM_182925.4(FLT4): c.3316G> A (p.Glu1106Lys) single nucleotide variant Pathogenic rs121909656 GRCh38 Chromosome 5, 180614083: 180614083
17 FLT4 NM_182925.4(FLT4): c.3323_3325delTCT (p.Phe1108del) deletion Pathogenic rs587776833 GRCh38 Chromosome 5, 180614074: 180614076
18 FLT4 NM_182925.4(FLT4): c.3323_3325delTCT (p.Phe1108del) deletion Pathogenic rs587776833 GRCh37 Chromosome 5, 180041074: 180041076
19 FLT4 NM_182925.4(FLT4): c.2563G> A (p.Ala855Thr) single nucleotide variant Pathogenic rs121909657 GRCh37 Chromosome 5, 180046749: 180046749
20 FLT4 NM_182925.4(FLT4): c.2563G> A (p.Ala855Thr) single nucleotide variant Pathogenic rs121909657 GRCh38 Chromosome 5, 180619749: 180619749

Expression for Lymphedema, Hereditary, Ia

Search GEO for disease gene expression data for Lymphedema, Hereditary, Ia.

Pathways for Lymphedema, Hereditary, Ia

GO Terms for Lymphedema, Hereditary, Ia

Sources for Lymphedema, Hereditary, Ia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....