LMPHM12
MCID: LYM161
MIFTS: 42

Lymphatic Malformation 12 (LMPHM12)

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 12

MalaCards integrated aliases for Lymphatic Malformation 12:

Name: Lymphatic Malformation 12 57 5
Central Conducting Lymphatic Anomaly 57 11
Lymphatic Malformation-7 11
Doid:0081030 14
Lmphm12 57
Ccla 57

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable severity
variable features may be present
affected individuals may be stillborn due to hydrops fetalis


Classifications:



External Ids:

Disease Ontology 11 DOID:0081030
OMIM® 57 620014
OMIM Phenotypic Series 57 PS153100

Summaries for Lymphatic Malformation 12

OMIM®: 57 Lymphatic malformation-12 (LMPHM12) is characterized by abnormalities in the development and function of major truncal lymphatic vessels, causing nonimmune hydrops fetalis that results in stillbirth in some cases. Other affected individuals experience postnatal subcutaneous lymphedema and chylothorax, with pleural and pericardial effusions and ascites (Byrne et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of lymphatic malformation, see LMPHM1 (153100). (620014) (Updated 08-Dec-2022)

MalaCards based summary: Lymphatic Malformation 12, also known as central conducting lymphatic anomaly, is related to capillary malformation-arteriovenous malformation 1 and lymphatic system disease. An important gene associated with Lymphatic Malformation 12 is MDFIC (MyoD Family Inhibitor Domain Containing), and among its related pathways/superpathways are ERK Signaling and Signal Transduction. Affiliated tissues include placenta, testis and lymph node, and related phenotypes are inguinal hernia and hyperkeratosis

Disease Ontology: 11 A lymphatic system disease that is characterized by dysfunction of the thoracic duct or cisterna chyli, leading to a retrograde flux of lymphatic fluid or abnormal drainage of lymphatic fluid and that has material basis in heterozygous mutation in the EPHB4 gene on chromosome 7q22.

Related Diseases for Lymphatic Malformation 12

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 Lymphatic Malformation 10
Lymphatic Malformation 11 Lymphatic Malformation 12

Diseases related to Lymphatic Malformation 12 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 49)
# Related Disease Score Top Affiliating Genes
1 capillary malformation-arteriovenous malformation 1 30.4 RASA1 EPHB4
2 lymphatic system disease 10.3
3 weber syndrome 10.1 RASA1 EPHB4
4 digeorge syndrome 10.1
5 down syndrome 10.1
6 ascites, chylous 10.1
7 hydrops fetalis, nonimmune 10.1
8 chromosome 22q11.2 deletion syndrome, distal 10.1
9 lymphatic malformation 7 10.1
10 hereditary lymphedema i 10.1
11 lymphangioma 10.1
12 hemangioma 10.1
13 pyogenic granuloma 10.1 EPHB4 EFNB2
14 hemangioma of intra-abdominal structure 10.1 SYNGAP1 RASA1
15 taylor's syndrome 10.1 SYNGAP1 RASA1
16 angiokeratoma circumscriptum 10.1 SYNGAP1 RASA1
17 capillary lymphangioma 10.0 SYNGAP1 RASA1
18 intracranial structure hemangioma 10.0 SYNGAP1 RASA1
19 intracranial cavernous angioma 10.0 SYNGAP1 RASA1
20 venous malformations, multiple cutaneous and mucosal 10.0 SYNGAP1 RASA1
21 congenital lipomatous overgrowth, vascular malformations, and epidermal nevi 10.0 SYNGAP1 RASA1
22 lymphedema-distichiasis syndrome 10.0 EPHB4 EFNB2
23 aspergillosis 10.0
24 invasive aspergillosis 10.0
25 capillary hemangioma 10.0 SYNGAP1 RASA1
26 sturge-weber syndrome 10.0 SYNGAP1 RASA1
27 infiltrating angiolipoma 9.9 SYNGAP1 RASA1 EPHB4
28 klippel-trenaunay-weber syndrome 9.9 SYNGAP1 RASA1 EPHB4
29 cardiovascular organ benign neoplasm 9.9 SYNGAP1 RASA1 EPHB4
30 pylorospasm 9.9 RASA2 A2ML1
31 proteus syndrome 9.9 SYNGAP1 RASA1
32 chylothorax, congenital 9.9 SOS2 EFNB2
33 trophoblastic neoplasm 9.8 RASA2 RASA1
34 nevus, epidermal 9.7 SYNGAP1 RASA1
35 pseudo-turner syndrome 9.7 SOS2 RRAS2
36 hereditary hemorrhagic telangiectasia 9.7 SYNGAP1 RASA1 EPHB4 EFNB2
37 noonan syndrome-like disorder with loose anagen hair 9.7 SOS2 RASA2
38 gingival fibromatosis 9.6 SOS2 RASA2 RASA1
39 pulmonary valve stenosis 9.5 SOS2 RASA2 A2ML1
40 pulmonary valve disease 9.5 SOS2 RASA2 A2ML1
41 juvenile myelomonocytic leukemia 9.4 SOS2 RRAS2 RASA2
42 arteriovenous malformations of the brain 9.4 SYNGAP1 RASA2 RASA1 EPHB4 EFNB2
43 arteriovenous malformation 9.4 SYNGAP1 RASA2 RASA1 EPHB4 EFNB2
44 neurofibromatosis-noonan syndrome 9.3 SOS2 RRAS2 RASA2 A2ML1
45 costello syndrome 9.1 SYNGAP1 SOS2 RASA2 RASA1 A2ML1
46 noonan syndrome with multiple lentigines 8.7 SYNGAP1 SOS2 RRAS2 RASA2 RASA1 ARAF
47 cardiofaciocutaneous syndrome 1 8.7 SYNGAP1 SOS2 RRAS2 RASA2 RASA1 ARAF
48 rasopathy 8.7 SYNGAP1 SOS2 RRAS2 RASA2 RASA1 ARAF
49 noonan syndrome 1 8.7 SYNGAP1 SOS2 RRAS2 RASA2 RASA1 ARAF

Graphical network of the top 20 diseases related to Lymphatic Malformation 12:



Diseases related to Lymphatic Malformation 12

Symptoms & Phenotypes for Lymphatic Malformation 12

Human phenotypes related to Lymphatic Malformation 12:

30 (show all 12)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 inguinal hernia 30 Very rare (1%) HP:0000023
2 hyperkeratosis 30 Very rare (1%) HP:0000962
3 lymphedema 30 Very rare (1%) HP:0001004
4 neonatal respiratory distress 30 Very rare (1%) HP:0002643
5 polyhydramnios 30 Very rare (1%) HP:0001561
6 fetal ascites 30 Very rare (1%) HP:0001791
7 hydrocele testis 30 Very rare (1%) HP:0000034
8 recurrent upper and lower respiratory tract infections 30 Very rare (1%) HP:0200117
9 nonimmune hydrops fetalis 30 Very rare (1%) HP:0001790
10 pleural thickening 30 Very rare (1%) HP:0031944
11 fetal pericardial effusion 30 Very rare (1%) HP:0025671
12 fetal chylothorax 30 Very rare (1%) HP:0025677

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Head And Neck Eyes:
ptosis
edema around eyes
edema of eyelids

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Chest:
chylothorax
dilated thoracic duct
hypoplastic or absent thoracic duct

Genitourinary External Genitalia Male:
hydrocele

Skin Nails Hair Skin:
subcutaneous edema
large cutaneous lymph channels
lymphedema below the knees

Abdomen:
ascites
retrograde mesenteric lymph flow

Cardiovascular Heart:
mitral valve prolapse
ventricular septal defect
pericardial effusion

Respiratory Lung:
pulmonary hypoplasia
frequent infections
pleural effusions, recurrent chylous

Cardiovascular Vascular:
patent foramen ovale

Prenatal Manifestations:
hydrops fetalis, nonimmune

Prenatal Manifestations Placenta And Umbilical Cord:
edematous placenta

Clinical features from OMIM®:

620014 (Updated 08-Dec-2022)

GenomeRNAi Phenotypes related to Lymphatic Malformation 12 according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.4 ARAF EPHB4
2 Decreased viability GR00221-A-2 9.4 EPHB4
3 Decreased viability GR00221-A-3 9.4 RASA1
4 Decreased viability GR00221-A-4 9.4 ARAF EPHB4 RASA1 RASA2
5 Decreased viability GR00301-A 9.4 EPHB4
6 Decreased viability GR00381-A-1 9.4 RASA1
7 Decreased viability GR00386-A-1 9.4 RASA1
8 Decreased viability GR00402-S-2 9.4 EPHB4

Drugs & Therapeutics for Lymphatic Malformation 12

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Lymphatic Anomalies Registry for the Assessment of Outcome Data Recruiting NCT02399527

Search NIH Clinical Center for Lymphatic Malformation 12

Genetic Tests for Lymphatic Malformation 12

Anatomical Context for Lymphatic Malformation 12

Organs/tissues related to Lymphatic Malformation 12:

MalaCards : Placenta, Testis, Lymph Node, Breast, Liver

Publications for Lymphatic Malformation 12

Articles related to Lymphatic Malformation 12:

(show top 50) (show all 71)
# Title Authors PMID Year
1
Pathogenic variants in MDFIC cause recessive central conducting lymphatic anomaly with lymphedema. 62 57 5
35235341 2022
2
A neonatal case of central conducting lymphatic anomaly successfully treated with sirolimus. 62
35652569 2022
3
Non-Surgical Transversal Dentoalveolar Compensation with Completely Customized Lingual Appliances versus Surgically Assisted Rapid Palatal Expansion in Adults-The Amount of Posterior Crossbite Correction. 62
36422069 2022
4
Double Valorization for a Discard-α-Chitin and Calcium Lactate Production from the Crab Polybius henslowii Using a Deep Eutectic Solvent Approach. 62
36421995 2022
5
Pain perception following computer-controlled versus conventional dental anesthesia: randomized controlled trial. 62
36138388 2022
6
Genetics etiologies and genotype phenotype correlations in a cohort of individuals with central conducting lymphatic anomaly. 62
35606495 2022
7
Correction to: Genetics etiologies and genotype phenotype correlations in a cohort of individuals with central conducting lymphatic anomaly. 62
35654890 2022
8
Optimization of Ultrasonic-Assisted Extraction (UAE) Method Using Natural Deep Eutectic Solvent (NADES) to Increase Curcuminoid Yield from Curcuma longa L., Curcuma xanthorrhiza, and Curcuma mangga Val. 62
36144813 2022
9
Lymphatic Anomalies in Children: Update on Imaging Diagnosis, Genetics, and Treatment. 62
35043669 2022
10
Lymphatic Phenotype of Noonan Syndrome: Innovative Diagnosis and Possible Implications for Therapy. 62
35683512 2022
11
Is dentin biomodification with collagen cross-linking agents effective for improving dentin adhesion? A systematic review and meta-analysis. 62
35692222 2022
12
Layer 6A Pyramidal Cell Subtypes Form Synaptic Microcircuits with Distinct Functional and Structural Properties. 62
34628499 2022
13
Combination Strategy of Genetic Dereplication and Manipulation of Epigenetic Regulators Reveals a Novel Compound from Plant Endophytic Fungus. 62
35409046 2022
14
Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies-Insights From a Retrospective Case Series. 62
35676905 2022
15
Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition. 62
36238151 2022
16
Objective treatment outcome assessment of a completely customized lingual appliance: A retrospective study. 62
34305012 2021
17
Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. 62
33580918 2021
18
Janus-faced EPHB4-associated disorders: novel pathogenic variants and unreported intrafamilial overlapping phenotypes. 62
33864021 2021
19
Chylous cyst-venous shunt for the management of central conducting lymphatic anomaly. 62
33997561 2021
20
Class II correction by maxillary en masse distalization using a completely customized lingual appliance and a novel mini-screw anchorage concept - preliminary results. 62
34187487 2021
21
Expanded phenotypic spectrum of JAG1-associated diseases: Central conducting lymphatic anomaly with a pathogenic variant in JAG1. 62
33433009 2021
22
Likelihood of myocardial infarction, revascularization and death following catheterization laboratory activation in patients with vs. without both chest pain and ST elevation. 62
32541211 2021
23
CCLA: an accurate method and web server for cancer cell line authentication using gene expression profiles. 62
32510568 2021
24
Laryngotracheal Reconstruction in a Patient With a Central Conducting Lymphatic Anomaly. 62
32902851 2021
25
Controlling incisor torque with completely customized lingual appliances. 62
32472341 2020
26
Surgical Residents as Certified Bilingual Speakers: A Quality Improvement Initiative. 62
32165106 2020
27
Inhibition of jasmonate-mediated plant defences by the fungal metabolite higginsianin B. 62
32006004 2020
28
Liver lipid metabolism disruption in cancer cachexia is aggravated by cla supplementation -induced inflammation. 62
30322784 2019
29
Regulation of subtelomeric fungal secondary metabolite genes by H3K4me3 regulators CclA and KdmB. 62
31165508 2019
30
ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor. 62
31263281 2019
31
The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies. 62
31196128 2019
32
H3K4 trimethylation by CclA regulates pathogenicity and the production of three families of terpenoid secondary metabolites in Colletotrichum higginsianum. 62
30924614 2019
33
Factors Associated With Accuracy of Self-Assessment Compared With Tested Non-English Language Proficiency Among Primary Care Providers. 62
30844905 2019
34
Deleting a Chromatin Remodeling Gene Increases the Diversity of Secondary Metabolites Produced by Colletotrichum higginsianum. 62
30776231 2019
35
Baculovirus IE2 Interacts with Viral DNA through Daxx To Generate an Organized Nuclear Body Structure for Gene Activation in Vero Cells. 62
30728268 2019
36
Lymphaticovenous bypass of the thoracic duct for the treatment of chylous leak in central conducting lymphatic anomalies. 62
30292452 2019
37
Evidence of a Demethylase-Independent Role for the H3K4-Specific Histone Demethylases in Aspergillus nidulans and Fusarium graminearum Secondary Metabolism. 62
31456754 2019
38
Speed and energy optimized quasi-delay-insensitive block carry lookahead adder. 62
31226125 2019
39
Abdominal lymphatic malformations. 62
29796772 2018
40
Quality of occlusal outcome following space closure in cases of lower second premolar aplasia using lingual orthodontic molar mesialization without maxillary counterbalancing extraction. 62
30249268 2018
41
Pathogenic variant in EPHB4 results in central conducting lymphatic anomaly. 62
29905864 2018
42
[Abdominal lymphatic malformations. German version]. 62
29242954 2018
43
Single tooth torque correction in the lower frontal area by a completely customized lingual appliance. 62
29017523 2017
44
Identification of an itaconic acid degrading pathway in itaconic acid producing Aspergillus terreus. 62
27102125 2016
45
Imaging features of kaposiform lymphangiomatosis. 62
27053281 2016
46
McCormick et al. A Case of a Central Conducting Lymphatic Anomaly Responsive to Sirolimus. Pediatrics. 2016;137(1):e20152694. 62
27033110 2016
47
A Case of a Central Conducting Lymphatic Anomaly Responsive to Sirolimus. 62
26729539 2016
48
An overproduction of astellolides induced by genetic disruption of chromatin-remodeling factors in Aspergillus oryzae. 62
26126743 2016
49
Stress response and adaptation of Listeria monocytogenes 08-5923 exposed to a sublethal dose of carnocyclin A. 62
24747893 2014
50
Relationship between self-assessed and tested non-English-language proficiency among primary care providers. 62
24556893 2014

Variations for Lymphatic Malformation 12

ClinVar genetic disease variations for Lymphatic Malformation 12:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MDFIC NM_001166345.3(MDFIC):c.391dup (p.Met131fs) DUP Pathogenic
1702938 GRCh37: 7:114619728-114619729
GRCh38: 7:114979673-114979674
2 MDFIC NM_001166345.3(MDFIC):c.732T>G (p.Phe244Leu) SNV Pathogenic
1702939 GRCh37: 7:114655980-114655980
GRCh38: 7:115015926-115015926
3 MDFIC NM_001166345.3(MDFIC):c.371del (p.Leu123_Ser124insTer) DEL Pathogenic
1702940 GRCh37: 7:114619714-114619714
GRCh38: 7:114979659-114979659
4 MDFIC NM_001166345.3(MDFIC):c.187G>T (p.Gly63Ter) SNV Pathogenic
1702941 GRCh37: 7:114582422-114582422
GRCh38: 7:114942367-114942367

Expression for Lymphatic Malformation 12

Search GEO for disease gene expression data for Lymphatic Malformation 12.

Pathways for Lymphatic Malformation 12

Pathways related to Lymphatic Malformation 12 according to GeneCards Suite gene sharing:

(show all 24)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.52 ARAF EPHB4 RASA1 RRAS2 SOS2 SYNGAP1
2 13.48 SYNGAP1 SOS2 RRAS2 RASA2 RASA1 ARAF
3
Show member pathways
13.12 SYNGAP1 SOS2 RRAS2 RASA2 RASA1 ARAF
4
Show member pathways
12.58 SOS2 RRAS2 RASA1 ARAF
5
Show member pathways
12.38 SOS2 RRAS2 ARAF
6
Show member pathways
12.33 RASA1 EPHB4 EFNB2
7
Show member pathways
12.2 SOS2 RASA2 RASA1 ARAF
8
Show member pathways
12.15 SOS2 RASA1 ARAF
9
Show member pathways
12.15 SOS2 RRAS2 RASA1
10
Show member pathways
12.15 SOS2 RRAS2 RASA1 ARAF
11
Show member pathways
12.09 SOS2 RASA1 EPHB4 EFNB2
12
Show member pathways
12.01 ARAF EPHB4 RASA1 RRAS2 SOS2
13
Show member pathways
12 SOS2 RRAS2 ARAF
14 11.94 SOS2 RRAS2 RASA2 RASA1 ARAF
15
Show member pathways
11.93 SOS2 RRAS2 RASA1
16
Show member pathways
11.89 SOS2 RRAS2 ARAF
17
Show member pathways
11.81 RRAS2 RASA1 ARAF
18 11.62 SYNGAP1 SOS2 RRAS2 RASA2 RASA1
19 11.24 SOS2 ARAF
20
Show member pathways
11.2 RRAS2 RASA2 RASA1
21 11.17 SOS2 RASA1
22 11 SOS2 ARAF
23 10.75 EFNB2 EPHB4
24
Show member pathways
10.43 SYNGAP1 SOS2 RASA2 RASA1

GO Terms for Lymphatic Malformation 12

Biological processes related to Lymphatic Malformation 12 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Ras protein signal transduction GO:0007265 9.73 SYNGAP1 SOS2 RRAS2
2 blood vessel morphogenesis GO:0048514 9.67 RASA1 EFNB2
3 cell migration involved in sprouting angiogenesis GO:0002042 9.62 EPHB4 EFNB2
4 regulation of GTPase activity GO:0043087 9.55 RASA1 RASA2 SYNGAP1
5 ephrin receptor signaling pathway GO:0048013 9.43 RASA1 EPHB4 EFNB2
6 negative regulation of Ras protein signal transduction GO:0046580 9.1 SYNGAP1 RASA2 RASA1

Sources for Lymphatic Malformation 12

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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