LMPHM6
MCID: LYM149
MIFTS: 34

Lymphatic Malformation 6 (LMPHM6)

Categories: Cancer diseases, Cardiovascular diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Neuronal diseases, Oral diseases, Rare diseases, Reproductive diseases, Respiratory diseases, Skin diseases
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Aliases & Classifications for Lymphatic Malformation 6

MalaCards integrated aliases for Lymphatic Malformation 6:

Name: Lymphatic Malformation 6 57 73 28 5 38
Generalized Lymphatic Dysplasia of Fotiou 57 73
Lymphedema, Hereditary, Iii 73 16
Lmphm6 57 73
Lymphedema, Hereditary, Iii, Formerly 57
Lymphedema, Hereditary, 3 73
Lmph3, Formerly 57
Lmph3 73

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable phenotype


Classifications:



Summaries for Lymphatic Malformation 6

OMIM®: 57 Lymphatic malformation-6 is a form of generalized lymphatic dysplasia (GLD), which is characterized by a uniform, widespread lymphedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions. In LMPHM6, there is a high incidence of nonimmune hydrops fetalis (NIHF) with either death or complete resolution of the neonatal edema, but childhood onset of lymphedema with or without systemic involvement also occurs. Mild facial edema is often present. Patients have normal intelligence and no seizures (summary by Fotiou et al., 2015). For a discussion of genetic heterogeneity of lymphatic malformation, see 153100. (616843) (Updated 08-Dec-2022)

MalaCards based summary: Lymphatic Malformation 6, also known as generalized lymphatic dysplasia of fotiou, is related to piezo1-related generalized lymphatic dysplasia with non-immune hydrops fetalis and lymphangioma. An important gene associated with Lymphatic Malformation 6 is PIEZO1 (Piezo Type Mechanosensitive Ion Channel Component 1). Affiliated tissues include testis and skin, and related phenotypes are splenomegaly and short stature

UniProtKB/Swiss-Prot: 73 A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM6 is an autosomal recessive, severe form manifesting as generalized lymphatic dysplasia. It is characterized by uniform, widespread swelling of all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions, and with a high incidence of non- immune hydrops fetalis.

Related Diseases for Lymphatic Malformation 6

Graphical network of the top 20 diseases related to Lymphatic Malformation 6:



Diseases related to Lymphatic Malformation 6

Symptoms & Phenotypes for Lymphatic Malformation 6

Human phenotypes related to Lymphatic Malformation 6:

30 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 splenomegaly 30 Very rare (1%) HP:0001744
2 short stature 30 Very rare (1%) HP:0004322
3 micrognathia 30 Very rare (1%) HP:0000347
4 epicanthus 30 Very rare (1%) HP:0000286
5 atrial septal defect 30 Very rare (1%) HP:0001631
6 cellulitis 30 Very rare (1%) HP:0100658
7 chylothorax 30 Very rare (1%) HP:0010310
8 deep venous thrombosis 30 Very rare (1%) HP:0002625
9 intestinal lymphangiectasia 30 Very rare (1%) HP:0002593
10 prune belly 30 Very rare (1%) HP:0004392
11 scoliosis 30 HP:0002650
12 hypothyroidism 30 HP:0000821
13 hearing impairment 30 HP:0000365
14 global developmental delay 30 HP:0001263
15 gastroesophageal reflux 30 HP:0002020
16 lymphedema 30 HP:0001004
17 ascites 30 HP:0001541
18 webbed neck 30 HP:0000465
19 pectus excavatum 30 HP:0000767
20 polyhydramnios 30 HP:0001561
21 varicose veins 30 HP:0002619
22 periorbital edema 30 HP:0100539
23 cupped ear 30 HP:0000378
24 facial edema 30 HP:0000282
25 hydrocele testis 30 HP:0000034
26 generalized edema 30 HP:0007430
27 nonimmune hydrops fetalis 30 HP:0001790
28 genital edema 30 HP:0031188

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Skeletal Spine:
scoliosis

Abdomen Spleen:
splenomegaly

Abdomen Gastrointestinal:
gastroesophageal reflux
intestinal lymphangiectasia

Head And Neck Face:
micrognathia
facial swelling
recurrent facial cellulitis

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Head And Neck Eyes:
periorbital edema
epicanthic folds

Genitourinary External Genitalia Male:
genital edema
hydrocele

Head And Neck Ears:
simple ears
cupped ears
deafness, bilateral sensorineural (uncommon)

Prenatal Manifestations:
hydrops fetalis, nonimmune

Skin Nails Hair Skin:
granuloma annulare

Immunology:
normal immune profile

Endocrine Features:
hypothyroidism

Growth Height:
short stature

Abdomen External Features:
ascites
prune belly

Head And Neck Neck:
webbed neck
swelling of the neck

Cardiovascular Heart:
atrial septal defect

Cardiovascular Vascular:
varicose veins
generalized edema
deep vein thrombosis

Respiratory:
chylothorax
pleural effusions, bilateral

Genitourinary External Genitalia Female:
genital edema

Neurologic Central Nervous System:
developmental delay, mild

Chest Diaphragm:
amyoplasia of diaphragm

Muscle Soft Tissue:
lymphedema (primarily in lower limbs, but also arms in some patients)
cellulitis in lower limbs, recurrent
deep rerouting of lymph in lower limbs seen on lymphoscintigraphy
superficial rerouting of lymph through the skin

Clinical features from OMIM®:

616843 (Updated 08-Dec-2022)

GenomeRNAi Phenotypes related to Lymphatic Malformation 6 according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Weakly decreased NFAT1-GFP nuclear translocation GR00359-A 8.32 PIEZO1

Drugs & Therapeutics for Lymphatic Malformation 6

Search Clinical Trials, NIH Clinical Center for Lymphatic Malformation 6

Genetic Tests for Lymphatic Malformation 6

Genetic tests related to Lymphatic Malformation 6:

# Genetic test Affiliating Genes
1 Lymphatic Malformation 6 28 PIEZO1

Anatomical Context for Lymphatic Malformation 6

Organs/tissues related to Lymphatic Malformation 6:

MalaCards : Testis, Skin

Publications for Lymphatic Malformation 6

Articles related to Lymphatic Malformation 6:

# Title Authors PMID Year
1
Author Correction: Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. 5
31028252 2019
2
Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. 57
26333996 2015
3
Early onset lymphoedema, recessive form--a new form of genetic lymphoedema syndrome. 57
3769974 1986
4
Perinatal presentations of non-immune hydrops fetalis due to recessive PIEZO1 disease: a challenging fetal diagnosis. 62
36453701 2022
5
[Two cases of lymphatic malformation-6 caused by new variation in PIEZO1 gene]. 62
36319164 2022
6
A Novel Homozygous Missense Mutation of PIEZO1 Leading to Lymphatic Malformation-6 Identified in a Family With Three Adverse Pregnancy Outcomes due to Nonimmune Fetal Hydrops. 62
35646098 2022
7
PIEZO1 Hypomorphic Variants in Congenital Lymphatic Dysplasia Cause Shape and Hydration Alterations of Red Blood Cells. 62
30930797 2019

Variations for Lymphatic Malformation 6

ClinVar genetic disease variations for Lymphatic Malformation 6:

5 (show top 50) (show all 65)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIEZO1 NM_001142864.4(PIEZO1):c.6964G>T (p.Glu2322Ter) SNV Pathogenic
973951 rs774561483 GRCh37: 16:88782854-88782854
GRCh38: 16:88716446-88716446
2 PIEZO1 NM_001142864.4(PIEZO1):c.6511G>T (p.Val2171Phe) SNV Pathogenic
223131 rs370296725 GRCh37: 16:88783580-88783580
GRCh38: 16:88717172-88717172
3 PIEZO1 NM_001142864.4(PIEZO1):c.4888G>T (p.Glu1630Ter) SNV Pathogenic
223128 rs869025597 GRCh37: 16:88788693-88788693
GRCh38: 16:88722285-88722285
4 PIEZO1 NM_001142864.4(PIEZO1):c.6682C>T (p.Gln2228Ter) SNV Pathogenic
223129 rs869025598 GRCh37: 16:88783285-88783285
GRCh38: 16:88716877-88716877
5 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.1669+1G>A SNV Pathogenic
223132 rs869025600 GRCh37: 16:88801542-88801542
GRCh38: 16:88735134-88735134
6 PIEZO1 NM_001142864.4(PIEZO1):c.3796+1G>A SNV Pathogenic
223130 rs869025599 GRCh37: 16:88792954-88792954
GRCh38: 16:88726546-88726546
7 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.2263G>T (p.Glu755Ter) SNV Pathogenic
223127 rs869025596 GRCh37: 16:88800380-88800380
GRCh38: 16:88733972-88733972
8 PIEZO1 NM_001142864.4(PIEZO1):c.7289C>T (p.Pro2430Leu) SNV Pathogenic
223133 rs869025601 GRCh37: 16:88782368-88782368
GRCh38: 16:88715960-88715960
9 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.1264C>T (p.Gln422Ter) SNV Pathogenic
449461 rs934897228 GRCh37: 16:88803079-88803079
GRCh38: 16:88736671-88736671
10 PIEZO1 NM_001142864.4(PIEZO1):c.5773C>T (p.Arg1925Trp) SNV Pathogenic
973950 rs201442593 GRCh37: 16:88787052-88787052
GRCh38: 16:88720644-88720644
11 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.1381C>T (p.Gln461Ter) SNV Pathogenic
1707478 GRCh37: 16:88802732-88802732
GRCh38: 16:88736324-88736324
12 PIEZO1 NM_001142864.4(PIEZO1):c.4373_4387delinsCGGCAGCAGG (p.Val1458fs) INDEL Likely Pathogenic
916578 rs1904297127 GRCh37: 16:88789685-88789699
GRCh38: 16:88723277-88723291
13 PIEZO1 NM_001142864.4(PIEZO1):c.3197A>G (p.Asp1066Gly) SNV Likely Pathogenic
978719 rs1904552378 GRCh37: 16:88794069-88794069
GRCh38: 16:88727661-88727661
14 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.3191G>T (p.Cys1064Phe) SNV Likely Pathogenic
978720 rs1904821405 GRCh37: 16:88798119-88798119
GRCh38: 16:88731711-88731711
15 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.1297-1G>A SNV Likely Pathogenic
1698796 GRCh37: 16:88802817-88802817
GRCh38: 16:88736409-88736409
16 PIEZO1 NM_001142864.4(PIEZO1):c.3206G>A (p.Trp1069Ter) SNV Likely Pathogenic
599180 rs1166021430 GRCh37: 16:88794060-88794060
GRCh38: 16:88727652-88727652
17 PIEZO1 NM_001142864.4(PIEZO1):c.6208A>C (p.Lys2070Gln) SNV Likely Pathogenic
599181 rs1567659736 GRCh37: 16:88786325-88786325
GRCh38: 16:88719917-88719917
18 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.2664G>A (p.Glu888_Pro889=) SNV Uncertain Significance
1709589 GRCh37: 16:88799686-88799686
GRCh38: 16:88733278-88733278
19 PIEZO1 NM_001142864.4(PIEZO1):c.6901_6912del (p.Leu2301_Thr2304del) DEL Uncertain Significance
1709590 GRCh37: 16:88782981-88782992
GRCh38: 16:88716573-88716584
20 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.2492C>T (p.Ser831Leu) SNV Uncertain Significance
829803 rs1471934686 GRCh37: 16:88799858-88799858
GRCh38: 16:88733450-88733450
21 PIEZO1 NM_001142864.4(PIEZO1):c.7553G>C (p.Arg2518Pro) SNV Uncertain Significance
638426 rs774268616 GRCh37: 16:88782026-88782026
GRCh38: 16:88715618-88715618
22 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.3000C>A (p.Phe1000Leu) SNV Uncertain Significance
638427 rs568280615 GRCh37: 16:88798310-88798310
GRCh38: 16:88731902-88731902
23 PIEZO1 NM_001142864.4(PIEZO1):c.19G>C (p.Gly7Arg) SNV Uncertain Significance
1030204 rs1226315961 GRCh37: 16:88851354-88851354
GRCh38: 16:88784946-88784946
24 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.2401C>T (p.Arg801Cys) SNV Uncertain Significance
1030205 rs1021969177 GRCh37: 16:88800082-88800082
GRCh38: 16:88733674-88733674
25 PIEZO1 NM_001142864.4(PIEZO1):c.5743C>G (p.Arg1915Gly) SNV Uncertain Significance
1030206 rs13338527 GRCh37: 16:88787082-88787082
GRCh38: 16:88720674-88720674
26 PIEZO1 NM_001142864.4(PIEZO1):c.6211T>C (p.Cys2071Arg) SNV Uncertain Significance
1177414 GRCh37: 16:88786322-88786322
GRCh38: 16:88719914-88719914
27 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.3107G>A (p.Arg1036His) SNV Uncertain Significance
548456 rs769506340 GRCh37: 16:88798203-88798203
GRCh38: 16:88731795-88731795
28 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.2344G>A (p.Gly782Ser) SNV Uncertain Significance
242665 rs200970763 GRCh37: 16:88800139-88800139
GRCh38: 16:88733731-88733731
29 PIEZO1 NM_001142864.4(PIEZO1):c.4850C>T (p.Thr1617Met) SNV Uncertain Significance
987920 rs906425217 GRCh37: 16:88788731-88788731
GRCh38: 16:88722323-88722323
30 PIEZO1 NM_001142864.4(PIEZO1):c.3667G>A (p.Val1223Ile) SNV Likely Benign
446042 rs185326407 GRCh37: 16:88793155-88793155
GRCh38: 16:88726747-88726747
31 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.749T>C (p.Val250Ala) SNV Benign
440043 rs7184427 GRCh37: 16:88804734-88804734
GRCh38: 16:88738326-88738326
32 PIEZO1 NM_001142864.4(PIEZO1):c.4193C>T (p.Pro1398Leu) SNV Benign
440038 rs11645197 GRCh37: 16:88791458-88791458
GRCh38: 16:88725050-88725050
33 PIEZO1 NM_001142864.4(PIEZO1):c.4956-3T>C SNV Benign
381268 rs9935872 GRCh37: 16:88788477-88788477
GRCh38: 16:88722069-88722069
34 PIEZO1 NM_001142864.4(PIEZO1):c.6793A>G (p.Ile2265Val) SNV Benign
440035 rs1803382 GRCh37: 16:88783100-88783100
GRCh38: 16:88716692-88716692
35 PIEZO1 NM_001142864.4(PIEZO1):c.5629AAG[1] (p.Lys1878del) MICROSAT Benign
440036 rs3217718 GRCh37: 16:88787608-88787610
GRCh38: 16:88721200-88721202
36 PIEZO1 NM_001142864.4(PIEZO1):c.5569C>T (p.Pro1857Ser) SNV Benign
440037 rs35159887 GRCh37: 16:88787673-88787673
GRCh38: 16:88721265-88721265
37 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.1219A>G (p.Arg407Gly) SNV Benign
440039 rs13333358 GRCh37: 16:88803124-88803124
GRCh38: 16:88736716-88736716
38 PIEZO1 NM_001142864.4(PIEZO1):c.7059T>C (p.Pro2353=) SNV Benign
440040 rs2290902 GRCh37: 16:88782676-88782676
GRCh38: 16:88716268-88716268
39 PIEZO1 NM_001142864.4(PIEZO1):c.6642G>C (p.Leu2214=) SNV Benign
440041 rs8057031 GRCh37: 16:88783449-88783449
GRCh38: 16:88717041-88717041
40 PIEZO1 NM_001142864.4(PIEZO1):c.3969-5T>C SNV Benign
440042 rs4782429 GRCh37: 16:88792097-88792097
GRCh38: 16:88725689-88725689
41 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.635-8C>T SNV Benign
440044 rs11076706 GRCh37: 16:88804856-88804856
GRCh38: 16:88738448-88738448
42 PIEZO1 NM_001142864.4(PIEZO1):c.465+8C>T SNV Benign
440045 rs2242164 GRCh37: 16:88807878-88807878
GRCh38: 16:88741470-88741470
43 PIEZO1 NM_001142864.4(PIEZO1):c.248T>C (p.Ile83Thr) SNV Benign
440046 rs6500495 GRCh37: 16:88808743-88808743
GRCh38: 16:88742335-88742335
44 PIEZO1 NM_001142864.4(PIEZO1):c.63T>G (p.Ala21=) SNV Benign
440047 rs2911442 GRCh37: 16:88851310-88851310
GRCh38: 16:88784902-88784902
45 PIEZO1 NM_001142864.4(PIEZO1):c.6570A>G (p.Pro2190=) SNV Benign
440048 rs6500491 GRCh37: 16:88783521-88783521
GRCh38: 16:88717113-88717113
46 PIEZO1 NM_001142864.4(PIEZO1):c.5538C>G (p.Ala1846=) SNV Benign
440049 rs8043924 GRCh37: 16:88787704-88787704
GRCh38: 16:88721296-88721296
47 PIEZO1 NM_001142864.4(PIEZO1):c.4014T>C (p.Phe1338=) SNV Benign
440050 rs4782430 GRCh37: 16:88792047-88792047
GRCh38: 16:88725639-88725639
48 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.1180G>C (p.Val394Leu) SNV Benign
440051 rs6500493 GRCh37: 16:88803982-88803982
GRCh38: 16:88737574-88737574
49 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.2865G>A (p.Gln955=) SNV Benign
618273 rs35597347 GRCh37: 16:88798869-88798869
GRCh38: 16:88732461-88732461
50 PIEZO1, LOC100289580 NM_001142864.4(PIEZO1):c.2329+19G>A SNV Benign
994106 rs2306050 GRCh37: 16:88800295-88800295
GRCh38: 16:88733887-88733887

Expression for Lymphatic Malformation 6

Search GEO for disease gene expression data for Lymphatic Malformation 6.

Pathways for Lymphatic Malformation 6

GO Terms for Lymphatic Malformation 6

Sources for Lymphatic Malformation 6

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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