LMPHM7
MCID: LYM150
MIFTS: 43

Lymphatic Malformation 7 (LMPHM7)

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 7

MalaCards integrated aliases for Lymphatic Malformation 7:

Name: Lymphatic Malformation 7 57 72
Hydrops Fetalis, Nonimmune, and/or Atrial Septal Defect, Susceptibility to 29 6
Central Conduction Lymphatic Anomaly 57 72
Hydrops Fetalis 44 70
Lmphm7 57 72
Hfasd 57 72
Hydrops Fetalis, Nonimmune, and/or Atrial Septal Defect; Hfasd 57
Hydrops Fetalis, Non-Immune, and/or Atrial Septal Defect 72
Hydrops Fetalis, Nonimmune, and/or Atrial Septal Defect 57
Lymphatic Malformation, Type 7 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
variable expressivity
variable severity
variability in age of onset (prenatal to adolescence)
onset of hydrops fetalis in utero
hydrops fetalis is associated with high morbidity and mortality in the neonatal period
hydrops resolves spontaneously with time after the neonatal period

Inheritance:
autosomal dominant


HPO:

31
lymphatic malformation 7:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity


Classifications:



Summaries for Lymphatic Malformation 7

UniProtKB/Swiss-Prot : 72 Lymphatic malformation 7: 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. LMPHM7 is an autosomal dominant form with variable expressivity. Some individuals present with severe non-immune hydrops fetalis, which may cause perinatal demise or fully resolve after the neonatal period. Others present with no edema and have milder clinical features, such as atrial septal defect or varicose veins as adults.

MalaCards based summary : Lymphatic Malformation 7, also known as hydrops fetalis, nonimmune, and/or atrial septal defect, susceptibility to, is related to hydrops fetalis, nonimmune and immune hydrops fetalis, and has symptoms including edema and peau d'orange. An important gene associated with Lymphatic Malformation 7 is EPHB4 (EPH Receptor B4). The drug Anti-Arrhythmia Agents has been mentioned in the context of this disorder. Affiliated tissues include heart, placenta and brain, and related phenotypes are anemia and atrial septal defect

OMIM® : 57 LMPHM7 is an autosomal dominant disorder with variable expressivity. Some patients may develop severe nonimmune lymphatic-related hydrops fetalis (LRHF) in utero, resulting in early death, whereas others may have milder manifestations, such as atrial septal defect (ASD) or varicose veins as adults. The hydrops and/or swelling improves spontaneously in those who survive the neonatal period (summary by Martin-Almedina et al., 2016). For a discussion of genetic heterogeneity of lymphatic malformation, see 153100. (617300) (Updated 20-May-2021)

Related Diseases for Lymphatic Malformation 7

Diseases in the Rare Lymphatic Malformation family:

Lymphatic Malformation 1 Lymphatic Malformation 5
Lymphatic Malformation 2 Lymphatic Malformation 3
Lymphatic Malformation 4 Lymphatic Malformation 6
Lymphatic Malformation 7 Lymphatic Malformation 8
Lymphatic Malformation 9

Diseases related to Lymphatic Malformation 7 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 442)
# Related Disease Score Top Affiliating Genes
1 hydrops fetalis, nonimmune 12.2
2 immune hydrops fetalis 11.5
3 mucopolysaccharidosis, type vii 11.5
4 alpha-thalassemia 11.4
5 lymphatic malformation 8 11.4
6 ephb4-related lymphatic-related hydrops fetalis 11.4
7 piezo1-related generalized lymphatic dysplasia with non-immune hydrops fetalis 11.4
8 congenital disorder of glycosylation, type ia 11.3
9 hemoglobin h disease 11.3
10 lymphatic malformation 6 11.3
11 transaldolase deficiency 11.3
12 achondrogenesis, type ii 11.3
13 chondrodysplasia, blomstrand type 11.3
14 greenberg dysplasia 11.3
15 hypochondrogenesis 11.3
16 hydrops fetalis, nonimmune, with gracile bones and dysmorphism 11.2
17 gaucher's disease 11.2
18 galactosialidosis 11.2
19 glycoproteinosis 11.2
20 congenital dyserythropoietic anemia 11.2
21 free sialic acid storage disorders 11.2
22 multiple pterygium syndrome, escobar variant 11.1
23 hennekam syndrome 11.1
24 lymphangiectasia, pulmonary, congenital 11.1
25 pyruvate kinase deficiency of red cells 11.1
26 gaucher disease, perinatal lethal 11.1
27 arterial calcification of infancy 11.1
28 achondrogenesis 11.1
29 dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema 11.1
30 short-rib thoracic dysplasia 12 11.1
31 porphyria, congenital erythropoietic 11.1
32 pyknoachondrogenesis 11.1
33 megalencephaly-capillary malformation-polymicrogyria syndrome 11.1
34 congenital disorder of glycosylation, type ih 11.1
35 fetal erythroblastosis 11.1
36 fetal parvovirus syndrome 11.1
37 dyserythropoietic anemia and thrombocytopenia 11.1
38 thalassemia 10.9
39 polyhydramnios 10.7
40 cystic lymphangioma 10.6
41 down syndrome 10.6
42 teratoma 10.6
43 deficiency anemia 10.6
44 chorioangioma 10.6
45 mucopolysaccharidosis-plus syndrome 10.6
46 chromosomal triplication 10.6
47 hemolytic anemia 10.5
48 lymphangiectasis 10.5
49 pre-eclampsia 10.5
50 lysosomal storage disease 10.5

Graphical network of the top 20 diseases related to Lymphatic Malformation 7:



Diseases related to Lymphatic Malformation 7

Symptoms & Phenotypes for Lymphatic Malformation 7

Human phenotypes related to Lymphatic Malformation 7:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 anemia 31 occasional (7.5%) HP:0001903
2 atrial septal defect 31 occasional (7.5%) HP:0001631
3 lymphedema 31 HP:0001004
4 varicose veins 31 HP:0002619
5 respiratory distress 31 HP:0002098
6 abdominal distention 31 HP:0003270
7 pericardial effusion 31 HP:0001698
8 facial edema 31 HP:0000282
9 nonimmune hydrops fetalis 31 HP:0001790
10 pulmonary edema 31 HP:0100598

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Muscle Soft Tissue:
lymphedema
edema

Abdomen External Features:
abdominal distention

Respiratory Lung:
pulmonary edema
pleural effusions
abnormal large lymphatic structures seen on lung biopsy
abnormal retrograde pulmonary lymphatic perfusion of right lung seen on magnetic resonance lymphangiography
proliferation of lymphatic channels in the lungs

Prenatal Manifestations:
hydrops fetalis, nonimmune
nuchal translucency

Head And Neck Neck:
retrograde flow of contrast in lymphatics into neck

Chest:
retrograde flow of contrast in lymphatics into mediastinum
dilated and tortuous thoracic duct
lymphatic valves appear absent or dysfunctional

Abdomen Gastrointestinal:
diarrhea with fat-rich foods (in some patients)

Skin Nails Hair Skin Histology:
markedly increased dermal vascular structures

Respiratory:
respiratory distress
chylothoraces
hydrothoraces

Head And Neck Face:
facial edema

Hematology:
anemia (in some patients)

Cardiovascular Heart:
pericardial effusions
atrial septal defect (in some patients)

Cardiovascular Vascular:
prominent veins in lower limbs
varicose veins (in older patients)
venous stasis
superficial clots in lower limbs

Abdomen:
retrograde flow of contrast in lymphatics into retroperitoneum and abdomen
proliferation of lymphatic channels in retroperitoneum
retroperitoneal masses

Skeletal Spine:
proliferation of lymphatic channels around the spine

Clinical features from OMIM®:

617300 (Updated 20-May-2021)

UMLS symptoms related to Lymphatic Malformation 7:


edema; peau d'orange

Drugs & Therapeutics for Lymphatic Malformation 7

Drugs for Lymphatic Malformation 7 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anti-Arrhythmia Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Single-Center, Non-Randomized Study of the Safety and Efficacy of In Utero Hematopoietic Stem Cell Transplantation for the Treatment of Fetuses With Alpha Thalassemia Major Recruiting NCT02986698 Phase 1
2 Precision Medical Research of Non-immune Fetal Hydrops (NIFH)-From Prenatal Diagnosis to Intrauterine Treatment Unknown status NCT02956564
3 Hydrops: Diagnosing & Redefining Outcomes With Precision Study Recruiting NCT03412760
4 FAST Trial Registry: Prospective Observational Cohort Study of Fetal Atrial Flutter & Supraventricular Tachycardia Recruiting NCT03376438
5 Fetal Electrophysiologic Abnormalities in High-risk Pregnancies Associated With Fetal Demise Recruiting NCT03775954
6 Whole Exome Sequencing and Whole Genome Sequencing for Non-immune Fetal/Neonatal Hydrops Recruiting NCT03911531
7 Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops Fetalis by Massively Parallel Sequencing Not yet recruiting NCT04308603
8 Amniotic Fluid Tandem Mass Spectrometry for Pregnancies Complicated by Nonimmune Hydrops and Severe Symmetrical Intrauterine Growth Restriction-A Multicenter Prospective Pilot Cohort Study Terminated NCT00143039

Search NIH Clinical Center for Lymphatic Malformation 7

Cochrane evidence based reviews: hydrops fetalis

Genetic Tests for Lymphatic Malformation 7

Genetic tests related to Lymphatic Malformation 7:

# Genetic test Affiliating Genes
1 Hydrops Fetalis, Nonimmune, and/or Atrial Septal Defect, Susceptibility to 29 EPHB4

Anatomical Context for Lymphatic Malformation 7

MalaCards organs/tissues related to Lymphatic Malformation 7:

40
Heart, Placenta, Brain, Lung, Bone, Bone Marrow, Kidney

Publications for Lymphatic Malformation 7

Articles related to Lymphatic Malformation 7:

(show top 50) (show all 2271)
# Title Authors PMID Year
1
EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis. 6 61 57
27400125 2016
2
Pathogenic variant in EPHB4 results in central conducting lymphatic anomaly. 6 57
29905864 2018
3
Newborn with hydrops fetalis and a severe supraventricular arrhythmia. 61
31434639 2021
4
Ultrasound Features of Fetal Anemia Lessons From Hemoglobin Bart Disease. 61
32815580 2021
5
Hydrops fetalis in PKD1L1-related heterotaxy: Report of two foetuses and expanding the phenotypic and molecular spectrum. 61
33655537 2021
6
Neonatal hereditary spherocytosis caused by a de novo frameshift mutation of the SPTB gene characterized by hydrops fetalis: A case report. 61
33761640 2021
7
Hydrops fetalis with isolated massive ascites in a preterm neonate with rhesus disease. 61
33738630 2021
8
Congenital Chylothorax and Hydrops Fetalis: A Novel Neonatal Presentation of RASA1 Mutation. 61
33608416 2021
9
High diagnosis rate for nonimmune hydrops fetalis with prenatal clinical exome from the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study. 61
33686258 2021
10
Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency. 61
33737400 2021
11
Persistence of SARS-CoV-2 in the first trimester placenta leading to transplacental transmission and fetal demise from an asymptomatic mother. 61
33346816 2021
12
Novel compound heterozygous frameshift variants in WDR81 associated with congenital hydrocephalus 3 with brain anomalies: First Chinese prenatal case confirms WDR81 involvement. 61
33724704 2021
13
[Isolated fetal pericardial effusion follow-up: Should we worry?] 61
33781717 2021
14
Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy. 61
33547425 2021
15
Mucopolysaccharidosis type VII as a cause of recurrent Non-Immune Hydrops Fetalis: The first Tunisian case confirmed by Next-Generation Sequencing. 61
33382994 2021
16
Manifestations of thrombospondin type-1 domain-containing protein 1 gene mutation in an extremely premature infant with nonimmune hydrops fetalis. 61
33569873 2021
17
Neonatal Hydrops Simulation Model: A Technical Report. 61
33786242 2021
18
The role of chromosomal microarray analysis among fetuses with normal karyotype and single system anomaly or nonspecific sonographic findings. 61
32981064 2021
19
Nonimmune hydrops fetalis management from the perspective of fetal cardiologists: A single tertiary center experience from Egypt. 61
33074198 2021
20
Staged Management of Congenital Chylothorax With Hydrops Fetalis: An Insight Into EXIT Related Procedures. 61
33681104 2021
21
Outcomes of haemoglobin Bart's hydrops fetalis following intrauterine transfusion in Ontario, Canada. 61
32616558 2021
22
A systematic review of monogenic etiologies of nonimmune hydrops fetalis. 61
33082562 2021
23
Postnatal IVIG treatment for persistent anaemia in neonate due to congenital parvovirus infection. 61
33431449 2021
24
Outcome of 45,X fetuses with cystic hygroma: A systematic review. 61
33026168 2021
25
Case report of neonatal ductus venosus atresia. 61
32925113 2021
26
Prenatal diagnosis of abdominal lymphatic malformations. 61
33494985 2021
27
Obstetrician patterns of steroid administration for the prenatal management of congenital pulmonary airway malformations. 61
33164951 2021
28
Human parvovirus B19: a review of clinical and epidemiological aspects in Brazil. 61
33438475 2021
29
Evaluation of Pulmonary Hypoplasia in Various Congenital Anomalies with a Comparison of Two Conventional Methods of Assessment: Radial Alveolar Count (RAC) and Lung Weight: Body Weight Ratio (LBW). 61
33432563 2021
30
Non-immune hydrops fetalis was rare in Sweden during 1997-2015, but cases were associated with complications and poor prognosis. 61
32187745 2020
31
Prenatal and Postnatal Management of Intrauterine Pleural Effusions Associated with Nonimmune Hydrops Fetalis. 61
33321527 2020
32
Challenges in chronic transfusion for patients with thalassemia. 61
33275743 2020
33
Comprehensive screening for coexisting heterozygous α0-thalassemia in hemoglobin E trait. 61
32633642 2020
34
Prenatal Treatment of Congenital Cytomegalovirus With Valganciclovir: A Case Report. 61
32198512 2020
35
Rare Case of Fetal Permanent Junctional Reciprocating Tachycardia Refractory to Prenatal Antiarrhythmic Therapy. 61
33367217 2020
36
Identification and management of congenital parvovirus B19 infection. 61
32860469 2020
37
Prenatal delineation of a distinct lethal fetal syndrome caused by a homozygous truncating KIDINS220 variant. 61
32909676 2020
38
Intrauterine Fetal Blood Transfusion (IUBT) for Rh Incompatibility - 12 Years' Experience from Pakistan. 61
33222739 2020
39
Prenatal diagnosis and management of monozygotic twins discordant for severe fetal abnormalities. 61
33218418 2020
40
Nonimmune Hydrops Fetalis - More Than Meets the Eye? 61
33027567 2020
41
Hydrops fetalis associated with anti-CD36 antibodies in fetal and neonatal alloimmune thrombocytopenia: Possible underlying mechanism. 61
32720360 2020
42
Complete resolution of arrhythmia-induced hydrops fetalis in utero. 61
33040036 2020
43
Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis. 61
33027564 2020
44
A retrospective clinical analysis of 20 cases of congenital lung masses. 61
33108914 2020
45
New Insights of Human Parvovirus B19 in Modulating Erythroid Progenitor Cell Differentiation. 61
32412895 2020
46
Congenital Hemolytic Anemia Because of Glucose Phosphate Isomerase Deficiency: Identification of 2 Novel Missense Mutations in the GPI Gene. 61
31415279 2020
47
Prevalence of Alpha(α)-Thalassemia in Southeast Asia (2010-2020): A Meta-Analysis Involving 83,674 Subjects. 61
33050119 2020
48
A homozygous variant in growth and differentiation factor 2 (GDF2) may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis. 61
32618121 2020
49
Intrapericardial teratoma presenting hydrops fetalis in a 29-week preterm infant. 61
32808373 2020
50
A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound. 61
32627857 2020

Variations for Lymphatic Malformation 7

ClinVar genetic disease variations for Lymphatic Malformation 7:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 EPHB4 NM_004444.5(EPHB4):c.2345T>G (p.Ile782Ser) SNV Pathogenic 374837 rs1057519264 GRCh37: 7:100404181-100404181
GRCh38: 7:100806559-100806559
2 EPHB4 NM_004444.5(EPHB4):c.2216G>A (p.Arg739Gln) SNV Pathogenic 374836 rs1057519263 GRCh37: 7:100405105-100405105
GRCh38: 7:100807483-100807483
3 EPHB4 NM_004444.5(EPHB4):c.2334+1G>C SNV Pathogenic 599047 rs1562967463 GRCh37: 7:100404986-100404986
GRCh38: 7:100807364-100807364
4 EPHB4 NM_004444.5(EPHB4):c.2858_2859CT[1] (p.Leu954fs) Microsatellite Likely pathogenic 692019 rs1584651110 GRCh37: 7:100401186-100401187
GRCh38: 7:100803564-100803565

UniProtKB/Swiss-Prot genetic disease variations for Lymphatic Malformation 7:

72
# Symbol AA change Variation ID SNP ID
1 EPHB4 p.Arg739Gln VAR_078063 rs105751926
2 EPHB4 p.Ile782Ser VAR_078064 rs105751926

Expression for Lymphatic Malformation 7

Search GEO for disease gene expression data for Lymphatic Malformation 7.

Pathways for Lymphatic Malformation 7

GO Terms for Lymphatic Malformation 7

Sources for Lymphatic Malformation 7

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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