LMPHM6
MCID: LYM149
MIFTS: 31

Lymphatic Malformation 6 (LMPHM6)

Categories: Cardiovascular diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Lymphatic Malformation 6

MalaCards integrated aliases for Lymphatic Malformation 6:

Name: Lymphatic Malformation 6 57 72
Lymphedema, Hereditary, Iii 72 29 6 17
Generalized Lymphatic Dysplasia of Fotiou 57 72
Lmphm6 57 72
Lymphedema, Hereditary, Iii, Formerly; Lmph3, Formerly 57
Lymphedema, Hereditary, Iii, Formerly 57
Lymphedema, Hereditary, 3 72
Lmph3, Formerly 57
Lmph3 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype


HPO:

31
lymphatic malformation 6:
Inheritance autosomal recessive inheritance


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 20-May-2021)

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

UniProtKB/Swiss-Prot : 72 Lymphatic malformation 6: 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

Symptoms & Phenotypes for Lymphatic Malformation 6

Human phenotypes related to Lymphatic Malformation 6:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 31 very rare (1%) HP:0001744
2 short stature 31 very rare (1%) HP:0004322
3 micrognathia 31 very rare (1%) HP:0000347
4 epicanthus 31 very rare (1%) HP:0000286
5 atrial septal defect 31 very rare (1%) HP:0001631
6 cellulitis 31 very rare (1%) HP:0100658
7 chylothorax 31 very rare (1%) HP:0010310
8 deep venous thrombosis 31 very rare (1%) HP:0002625
9 prune belly 31 very rare (1%) HP:0004392
10 intestinal lymphangiectasia 31 very rare (1%) HP:0002593
11 scoliosis 31 HP:0002650
12 hypothyroidism 31 HP:0000821
13 hearing impairment 31 HP:0000365
14 global developmental delay 31 HP:0001263
15 gastroesophageal reflux 31 HP:0002020
16 lymphedema 31 HP:0001004
17 ascites 31 HP:0001541
18 webbed neck 31 HP:0000465
19 pectus excavatum 31 HP:0000767
20 polyhydramnios 31 HP:0001561
21 varicose veins 31 HP:0002619
22 periorbital edema 31 HP:0100539
23 cupped ear 31 HP:0000378
24 facial edema 31 HP:0000282
25 nonimmune hydrops fetalis 31 HP:0001790
26 hydrocele testis 31 HP:0000034
27 generalized edema 31 HP:0007430
28 genital edema 31 HP:0031188

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 20-May-2021)

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

26
# 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 Lymphedema, Hereditary, Iii 29 PIEZO1

Anatomical Context for Lymphatic Malformation 6

MalaCards organs/tissues related to Lymphatic Malformation 6:

40
Testis

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. 6
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
PIEZO1 Hypomorphic Variants in Congenital Lymphatic Dysplasia Cause Shape and Hydration Alterations of Red Blood Cells. 61
30930797 2019

Variations for Lymphatic Malformation 6

ClinVar genetic disease variations for Lymphatic Malformation 6:

6 (show all 26)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIEZO1 NM_001142864.4(PIEZO1):c.6511G>T (p.Val2171Phe) SNV Pathogenic 223131 rs370296725 GRCh37: 16:88783580-88783580
GRCh38: 16:88717172-88717172
2 PIEZO1 NM_001142864.4(PIEZO1):c.4888G>T (p.Glu1630Ter) SNV Pathogenic 223128 rs869025597 GRCh37: 16:88788693-88788693
GRCh38: 16:88722285-88722285
3 PIEZO1 NM_001142864.4(PIEZO1):c.6682C>T (p.Gln2228Ter) SNV Pathogenic 223129 rs869025598 GRCh37: 16:88783285-88783285
GRCh38: 16:88716877-88716877
4 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.1669+1G>A SNV Pathogenic 223132 rs869025600 GRCh37: 16:88801542-88801542
GRCh38: 16:88735134-88735134
5 PIEZO1 NM_001142864.4(PIEZO1):c.3796+1G>A SNV Pathogenic 223130 rs869025599 GRCh37: 16:88792954-88792954
GRCh38: 16:88726546-88726546
6 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.2263G>T (p.Glu755Ter) SNV Pathogenic 223127 rs869025596 GRCh37: 16:88800380-88800380
GRCh38: 16:88733972-88733972
7 PIEZO1 NM_001142864.4(PIEZO1):c.7289C>T (p.Pro2430Leu) SNV Pathogenic 223133 rs869025601 GRCh37: 16:88782368-88782368
GRCh38: 16:88715960-88715960
8 PIEZO1 NM_001142864.4(PIEZO1):c.6964G>T (p.Glu2322Ter) SNV Pathogenic 973951 GRCh37: 16:88782854-88782854
GRCh38: 16:88716446-88716446
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 GRCh37: 16:88787052-88787052
GRCh38: 16:88720644-88720644
11 PIEZO1 NM_001142864.4(PIEZO1):c.4373_4387delinsCGGCAGCAGG (p.Val1458fs) Indel Likely pathogenic 916578 GRCh37: 16:88789685-88789699
GRCh38: 16:88723277-88723291
12 PIEZO1 NM_001142864.4(PIEZO1):c.3197A>G (p.Asp1066Gly) SNV Likely pathogenic 978719 GRCh37: 16:88794069-88794069
GRCh38: 16:88727661-88727661
13 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.3191G>T (p.Cys1064Phe) SNV Likely pathogenic 978720 GRCh37: 16:88798119-88798119
GRCh38: 16:88731711-88731711
14 PIEZO1 NM_001142864.4(PIEZO1):c.3206G>A (p.Trp1069Ter) SNV Likely pathogenic 599180 rs1166021430 GRCh37: 16:88794060-88794060
GRCh38: 16:88727652-88727652
15 PIEZO1 NM_001142864.4(PIEZO1):c.6208A>C (p.Lys2070Gln) SNV Likely pathogenic 599181 rs1567659736 GRCh37: 16:88786325-88786325
GRCh38: 16:88719917-88719917
16 PIEZO1 NM_001142864.4(PIEZO1):c.7553G>C (p.Arg2518Pro) SNV Uncertain significance 638426 rs774268616 GRCh37: 16:88782026-88782026
GRCh38: 16:88715618-88715618
17 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.3000C>A (p.Phe1000Leu) SNV Uncertain significance 638427 rs568280615 GRCh37: 16:88798310-88798310
GRCh38: 16:88731902-88731902
18 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.2492C>T (p.Ser831Leu) SNV Uncertain significance 829803 rs1471934686 GRCh37: 16:88799858-88799858
GRCh38: 16:88733450-88733450
19 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.3107G>A (p.Arg1036His) SNV Uncertain significance 548456 rs769506340 GRCh37: 16:88798203-88798203
GRCh38: 16:88731795-88731795
20 PIEZO1 NM_001142864.4(PIEZO1):c.4850C>T (p.Thr1617Met) SNV Uncertain significance 987920 GRCh37: 16:88788731-88788731
GRCh38: 16:88722323-88722323
21 PIEZO1 NM_001142864.4(PIEZO1):c.19G>C (p.Gly7Arg) SNV Uncertain significance 1030204 GRCh37: 16:88851354-88851354
GRCh38: 16:88784946-88784946
22 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.2401C>T (p.Arg801Cys) SNV Uncertain significance 1030205 GRCh37: 16:88800082-88800082
GRCh38: 16:88733674-88733674
23 PIEZO1 NM_001142864.4(PIEZO1):c.5743C>G (p.Arg1915Gly) SNV Uncertain significance 1030206 GRCh37: 16:88787082-88787082
GRCh38: 16:88720674-88720674
24 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.2344G>A (p.Gly782Ser) SNV Uncertain significance 242665 rs200970763 GRCh37: 16:88800139-88800139
GRCh38: 16:88733731-88733731
25 PIEZO1 NM_001142864.4(PIEZO1):c.4193C>T (p.Pro1398Leu) SNV Benign 440038 rs11645197 GRCh37: 16:88791458-88791458
GRCh38: 16:88725050-88725050
26 PIEZO1 , LOC100289580 NM_001142864.4(PIEZO1):c.749T>C (p.Val250Ala) SNV Benign 440043 rs7184427 GRCh37: 16:88804734-88804734
GRCh38: 16:88738326-88738326

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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