LMPH1A
MCID: LYM144
MIFTS: 41

Lymphatic Malformation 1 (LMPH1A)

Categories: Cancer diseases, Cardiovascular diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Neuronal diseases, Oral diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Lymphatic Malformation 1

MalaCards integrated aliases for Lymphatic Malformation 1:

Name: Lymphatic Malformation 1 58
Milroy Disease 58 25 54 26 76
Nonne-Milroy Lymphedema 58 54 26 76
Primary Congenital Lymphedema 58 54 76
Hereditary Lymphedema Type I 54 26
Milroy's Disease 54 26
Pcl 58 76
Lymphedema, Hereditary, Ia, Formerly; Lmph1a, Formerly 58
Lymphedema, Hereditary, Type I, Formerly 58
Lymphedema, Hereditary, Ia, Formerly 58
Primary Congenital Lymphedema; Pcl 58
Congenital Hereditary Lymphedema 54
Lymphedema, Hereditary, Type Ia 41
Congenital Familial Lymphedema 26
Congenital Primary Lymphedema 54
Hereditary Lymphedema, Type I 25
Lymphedema Hereditary Type Ia 76
Milroy Congenital Lymphedema 25
Lymphedema, Hereditary, 1a 76
Lymphedema, Hereditary I 13
Lymphedema, Early-Onset 58
Hereditary Lymphedema 1 54
Early Onset Lymphedema 54
Lymphedema Early-Onset 76
Hereditary Lymphedema 54
Nonne-Milroy Syndrome 54
Nonne-Milroy Disease 54
Lmph1a, Formerly 58
Lmphm1 58
Lmph1a 76

Characteristics:

OMIM:

58
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:

33
lymphatic malformation 1:
Onset and clinical course congenital onset
Inheritance autosomal dominant inheritance


GeneReviews:

25
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 Lymphatic Malformation 1

NIH Rare Diseases : 54 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 : Lymphatic Malformation 1, also known as milroy disease, is related to hereditary lymphedema ii and hereditary lymphedema ic. An important gene associated with Lymphatic Malformation 1 is FLT4 (Fms Related Tyrosine Kinase 4). The drugs Paroxetine and Neurotransmitter Uptake Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include skin, prostate and testis, and related phenotypes are cellulitis and papilloma

Genetics Home Reference : 26 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 : 58 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 : 76 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 Lymphatic Malformation 1

Diseases in the Lymphatic Malformations family:

Lymphatic Malformation 1 Lymphatic Malformation 5
Lymphatic Malformation 2 Lymphatic Malformation 3
Lymphatic Malformation 4 Lymphatic Malformation 6
Lymphatic Malformation 7

Diseases related to Lymphatic Malformation 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 83)
# Related Disease Score Top Affiliating Genes
1 hereditary lymphedema ii 12.5
2 hereditary lymphedema ic 12.4
3 hereditary lymphedema id 12.4
4 hereditary lymphedema ia 12.4
5 hereditary lymphedema ib 12.4
6 plasma cell leukemia 12.2
7 hereditary lymphedema i 11.6
8 hereditary lymphedema 11.6
9 congenital lymphedema 11.6
10 lymphedema-distichiasis syndrome 11.4
11 lymphatic malformation 5 11.1
12 yellow nail syndrome 11.1
13 lymphatic malformation 4 11.1
14 lymphedema 10.7
15 tropical calcific pancreatitis 10.6
16 blood group, colton system 10.3
17 distichiasis 10.1
18 personality disorder 10.1
19 primary orthostatic tremor 10.1
20 lymphangiosarcoma 10.1
21 colorectal cancer 10.0
22 hairy nose tip 10.0
23 prostate cancer 10.0
24 prostate cancer, hereditary, 8 10.0
25 prostate cancer, hereditary, 6 10.0
26 spinal cord injury 10.0
27 uveitis 10.0
28 dermatitis 10.0
29 contact dermatitis 10.0
30 squamous cell carcinoma 10.0
31 hemangioendothelioma 10.0
32 retiform hemangioendothelioma 10.0
33 arthritis 10.0
34 desmoid tumor 10.0
35 sarcoma 10.0
36 diarrhea 10.0
37 lymphangioma 10.0
38 malignant fibroxanthoma 10.0
39 thrombocytosis 10.0
40 histiocytoma 10.0
41 fibrous histiocytoma 10.0
42 septic arthritis 10.0
43 undifferentiated pleomorphic sarcoma 10.0
44 breast cancer 9.9
45 hepatocellular carcinoma 9.9
46 lipomatosis, multiple 9.9
47 pheochromocytoma 9.9
48 neural tube defects 9.9
49 lung cancer 9.9
50 osteogenic sarcoma 9.9

Graphical network of the top 20 diseases related to Lymphatic Malformation 1:



Diseases related to Lymphatic Malformation 1

Symptoms & Phenotypes for Lymphatic Malformation 1

Human phenotypes related to Lymphatic Malformation 1:

33 (show all 11)
# Description HPO Frequency HPO Source Accession
1 cellulitis 33 very rare (1%) HP:0100658
2 papilloma 33 very rare (1%) HP:0012740
3 abnormal toenail morphology 33 very rare (1%) HP:0008388
4 prominent superficial veins 33 very rare (1%) HP:0001015
5 hydrocele testis 33 very rare (1%) HP:0000034
6 urethral stricture 33 very rare (1%) HP:0012227
7 predominantly lower limb lymphedema 33 very rare (1%) HP:0003550
8 hypoplasia of lymphatic vessels 33 very rare (1%) HP:0003759
9 nonimmune hydrops fetalis 33 very rare (1%) HP:0001790
10 hemangioma 33 HP:0001028
11 hyperkeratosis over edematous areas 33 HP:0007448

Symptoms via clinical synopsis from OMIM:

58
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

Drugs & Therapeutics for Lymphatic Malformation 1

Drugs for Lymphatic Malformation 1 (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 Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders Enrolling by invitation NCT00833599 NIRFLI with ICG
11 Histologic Analysis of the Lymphatic Vessels Used for Supermicrosurgical Lymphatico-venous Anastomoses in Lymphedema Recruiting NCT03465930
12 Oedema Study : Chroedem Recruiting NCT02914808
13 A Pilot Study to Evaluate the Feasibility and Potential Effectiveness of the Flexitouch System Head and Neck Treatment Recruiting NCT03332160 Not Applicable
14 Quality of Life Changes on Lower Extremity Lymphedema Patients Using an Advanced Pneumatic Compression Device (PCD) Recruiting NCT02661646

Search NIH Clinical Center for Lymphatic Malformation 1

Genetic Tests for Lymphatic Malformation 1

Anatomical Context for Lymphatic Malformation 1

MalaCards organs/tissues related to Lymphatic Malformation 1:

42
Skin, Prostate, Testis, Lung, Spinal Cord, Adrenal Gland

Publications for Lymphatic Malformation 1

Articles related to Lymphatic Malformation 1:

(show all 22)
# 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
Milroy Disease or Primary Congenital Lymphedema Associated With Invasive Squamous Cell Carcinoma. ( 27374380 )
2016
4
A NOVEL FLT4 GENE MUTATION AND MR LYMPHANGIOGRAPHY IN A CHINESE FAMILY WITH MILROY DISEASE. ( 26714373 )
2015
5
A novel FLT4 mutation identified in a patient with Milroy disease. ( 25109169 )
2014
6
Four generations of rare familial lymphedema (Milroy disease). ( 23751338 )
2013
7
FLT4/VEGFR3 and Milroy disease: novel mutations, a review of published variants and database update. ( 23074044 )
2013
8
Prenatal diagnosis of Milroy disease. ( 22021048 )
2011
9
Lymphatic dysfunction, not aplasia, underlies Milroy disease. ( 20536741 )
2010
10
Analysis of the coding regions of VEGFR3 and VEGFC in Milroy disease and other primary lymphoedemas. ( 19002718 )
2009
11
Puffy feet in an 11-month-old infant: a quiz. Milroy disease. ( 19997714 )
2009
12
Recessive primary congenital lymphoedema caused by a VEGFR3 mutation. ( 19289394 )
2009
13
Three children with Milroy disease and de novo mutations in VEGFR3. ( 17250670 )
2007
14
A novel VEGFR3 mutation causes Milroy disease. ( 17458866 )
2007
15
Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3. ( 16924388 )
2006
16
Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations. ( 16965327 )
2006
17
Milroy disease and the VEGFR-3 mutation phenotype. ( 15689446 )
2005
18
Verruciform xanthoma in association with milroy disease and leaky capillary syndrome. ( 12558846 )
2003
19
Identification of eight novel VEGFR-3 mutations in families with primary congenital lymphoedema. ( 12960217 )
2003
20
Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. ( 10856194 )
2000
21
Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. ( 10835628 )
2000
22
Hereditary lymphedema: evidence for linkage and genetic heterogeneity. ( 9817924 )
1998

Variations for Lymphatic Malformation 1

UniProtKB/Swiss-Prot genetic disease variations for Lymphatic Malformation 1:

76 (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 Lymphatic Malformation 1:

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 Lymphatic Malformation 1

Search GEO for disease gene expression data for Lymphatic Malformation 1.

Pathways for Lymphatic Malformation 1

GO Terms for Lymphatic Malformation 1

Sources for Lymphatic Malformation 1

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