MCID: MLT134
MIFTS: 48

Multiple Pterygium Syndrome, Lethal Type

Categories: Genetic diseases, Rare diseases, Fetal diseases

Aliases & Classifications for Multiple Pterygium Syndrome, Lethal Type

MalaCards integrated aliases for Multiple Pterygium Syndrome, Lethal Type:

Name: Multiple Pterygium Syndrome, Lethal Type 53 71 13 69
Lmps 53 49 55 71
Lethal Multiple Pterygium Syndrome 49 55 28
Autosomal Recessive Lethal Multiple Pterygium Syndrome 55
Pterygium Syndrome, Multiple, Lethal Type 53
Multiple Pterygium Syndrome Lethal Type 49
Pterygium Syndrome Multiple Lethal Type 49

Characteristics:

Orphanet epidemiological data:

55
lethal multiple pterygium syndrome
Inheritance: Autosomal recessive,X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
lethal


HPO:

31
multiple pterygium syndrome, lethal type:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Multiple Pterygium Syndrome, Lethal Type

NIH Rare Diseases : 49 Multiple pterygium syndrome lethal type is a very rare genetic condition affecting the skin, muscles and skeleton. It is characterized by minor facial abnormalities, prenatal growth deficiency, spine defects, joint contractures, and webbing (pterygia) of the neck, elbows, back of the knees, armpits, and fingers.  Fetuses with this condition are usually not born. Some of the prenatal complications include cystic hygroma, hydrops, diaphragmatic hernia, polyhydramnios, underdevelopment of the heart and lungs, microcephaly, bone fusions, joint dislocations, spinal fusion, and bone fractures. Both X-linked and autosomal recessive inheritance have been proposed.Mutations in the CHRNG, CHRNA1, and CHRND genes have been found to cause this condition. Last updated: 7/21/2011

MalaCards based summary : Multiple Pterygium Syndrome, Lethal Type, also known as lmps, is related to multiple pterygium syndrome, escobar variant and multiple pterygium syndrome, x-linked, and has symptoms including edema, hypertelorism and low-set ears. An important gene associated with Multiple Pterygium Syndrome, Lethal Type is CHRND (Cholinergic Receptor Nicotinic Delta Subunit), and among its related pathways/superpathways are CREB Pathway and Transmission across Chemical Synapses. Affiliated tissues include lung, bone and heart, and related phenotypes are Decreased shRNA abundance (Z-score < -2) and muscle

UniProtKB/Swiss-Prot : 71 Multiple pterygium syndrome, lethal type: Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.

Description from OMIM: 253290

Related Diseases for Multiple Pterygium Syndrome, Lethal Type

Diseases related to Multiple Pterygium Syndrome, Lethal Type via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 50)
# Related Disease Score Top Affiliating Genes
1 multiple pterygium syndrome, escobar variant 31.2 CHRNA1 CHRND CHRNG RYR1
2 multiple pterygium syndrome, x-linked 11.2
3 cystic lymphangioma 10.1 CHRND CHRNG
4 slow-channel congenital myasthenic syndrome 10.1 CHRNA1 CHRND
5 microphthalmia, isolated 1 10.0 CHRND CHRNG
6 omphalocele 9.9
7 hydranencephaly 9.9
8 uniparental disomy of chromosome 2 9.9
9 blood group, i system 9.8
10 hepatitis 9.8
11 hepatitis b 9.8
12 oligohydramnios 9.8 CHRNA1 CHRND CHRNG
13 congenital contractures 9.7 CHRNG RYR1
14 postsynaptic congenital myasthenic syndromes 9.7 CHRNA1 CHRND RAPSN
15 autoimmune disease 9.7
16 hepatocellular carcinoma 9.7
17 apocrine gland secretion, variation in 9.7
18 lymphoma, mucosa-associated lymphoid type 9.7
19 renal cell carcinoma, nonpapillary 9.7
20 celiac disease 1 9.7
21 aging 9.7
22 dermatitis, atopic 9.7
23 vitiligo-associated multiple autoimmune disease susceptibility 1 9.7
24 autoimmune disease 1 9.7
25 ovarian cancer 1 9.7
26 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 9.7
27 diabetes mellitus 9.7
28 lymphoma 9.7
29 tonsillitis 9.7
30 brucellosis 9.7
31 esophagitis 9.7
32 squamous cell carcinoma 9.7
33 melanoma 9.7
34 cystadenoma 9.7
35 dermatitis 9.7
36 adenocarcinoma 9.7
37 ovarian cystadenoma 9.7
38 embryonal carcinoma 9.7
39 pustulosis of palm and sole 9.7
40 lymphoepithelioma-like carcinoma 9.7
41 psoriasis 9.7
42 neuromuscular junction disease 9.7 CHRNA1 CHRND RAPSN
43 congenital myasthenic syndrome 9.7 CHRNA1 CHRND RAPSN
44 congenital structural myopathy 9.6 NEB RYR1
45 central core disease of muscle 9.6 NEB RYR1
46 myopathy, congenital 9.5 NEB RYR1
47 muscle tissue disease 9.4 NEB RYR1
48 fetal akinesia deformation sequence 9.4 CHRNA1 CHRND CHRNG RAPSN
49 distal arthrogryposis 9.4 RAPSN RYR1
50 myasthenia gravis 9.1 CHRNA1 CHRNG RAPSN RYR1

Graphical network of the top 20 diseases related to Multiple Pterygium Syndrome, Lethal Type:



Diseases related to Multiple Pterygium Syndrome, Lethal Type

Symptoms & Phenotypes for Multiple Pterygium Syndrome, Lethal Type

Symptoms via clinical synopsis from OMIM:

53
HeadAndNeckEyes:
hypertelorism
epicanthal folds

HeadAndNeckMouth:
cleft palate
cleft lip/palate

GrowthOther:
intrauterine growth retardation

ChestRibsSternumClaviclesAndScapulae:
thin ribs

MetabolicFeatures:
malignant hyperthermia

HeadAndNeckNose:
flat nose

Skeletal:
fractures
congenital bone fusions

RespiratoryLung:
hypoplastic lungs

CardiovascularHeart:
hypoplastic heart

MuscleSoftTissue:
generalized amyoplasia

HeadAndNeckEars:
low-set ears

HeadAndNeckFace:
micrognathia
dysmorphic facies

HeadAndNeckNeck:
cystic hygroma
jugular lymphatic obstruction sequence

PrenatalManifestationsAmnioticFluid:
polyhydramnios

SkinNailsHairSkin:
multiple pterygia

SkeletalLimbs:
flexion contractures
joint dislocations

PrenatalManifestations:
hydrops

SkeletalSpine:
spinal fusion
abnormal cervical curvature

SkeletalHands:
microbrachydactyly

NeurologicCentralNervousSystem:
early severe fetal akinesia sequence


Clinical features from OMIM:

253290

Human phenotypes related to Multiple Pterygium Syndrome, Lethal Type:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 edema 31 HP:0000969
2 hypertelorism 31 HP:0000316
3 low-set ears 31 HP:0000369
4 joint dislocation 31 HP:0001373
5 abnormal facial shape 31 HP:0001999
6 flexion contracture 31 HP:0001371
7 cleft palate 31 HP:0000175
8 micrognathia 31 HP:0000347
9 epicanthus 31 HP:0000286
10 intrauterine growth retardation 31 HP:0001511
11 cystic hygroma 31 HP:0000476
12 depressed nasal ridge 31 HP:0000457
13 thin ribs 31 HP:0000883
14 polyhydramnios 31 HP:0001561
15 vertebral fusion 31 HP:0002948
16 malignant hyperthermia 31 HP:0002047
17 short finger 31 HP:0009381
18 pulmonary hypoplasia 31 HP:0002089
19 increased susceptibility to fractures 31 HP:0002659
20 akinesia 31 HP:0002304
21 multiple pterygia 31 HP:0001040
22 fetal akinesia sequence 31 HP:0001989
23 hypoplastic heart 31 HP:0001961
24 abnormal cervical curvature 31 HP:0005905
25 amyoplasia 31 HP:0003634

UMLS symptoms related to Multiple Pterygium Syndrome, Lethal Type:


edema

GenomeRNAi Phenotypes related to Multiple Pterygium Syndrome, Lethal Type according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-155 8.62 CHRNA1 RAPSN

MGI Mouse Phenotypes related to Multiple Pterygium Syndrome, Lethal Type:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 8.92 CHRNG NEB RAPSN RYR1

Drugs & Therapeutics for Multiple Pterygium Syndrome, Lethal Type

Search Clinical Trials , NIH Clinical Center for Multiple Pterygium Syndrome, Lethal Type

Genetic Tests for Multiple Pterygium Syndrome, Lethal Type

Genetic tests related to Multiple Pterygium Syndrome, Lethal Type:

# Genetic test Affiliating Genes
1 Lethal Multiple Pterygium Syndrome 28 CHRNA1 CHRND CHRNG

Anatomical Context for Multiple Pterygium Syndrome, Lethal Type

MalaCards organs/tissues related to Multiple Pterygium Syndrome, Lethal Type:

38
Lung, Bone, Heart, Skin

Publications for Multiple Pterygium Syndrome, Lethal Type

Articles related to Multiple Pterygium Syndrome, Lethal Type:

(show all 42)
# Title Authors Year
1
Prenatal detection of uniparental disomy of chromosome 2 carrying a CHRND pathogenic variant that causes lethal multiple pterygium syndrome. ( 29399782 )
2018
2
Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome. ( 25476234 )
2014
3
LMP gene promoter hypermethylation is a mechanism for its down regulation in Kazak's esophageal squamous cell carcinomas. ( 23283737 )
2013
4
Prenatal Diagnosis of Lethal Multiple Pterygium Syndrome Using Two-and Three-Dimensional Ultrasonography. ( 23230547 )
2012
5
Nuclear P27 expression in benign, borderline (LMP) and invasive tumors of the ovary and its association with prognosis: a gynecologic oncology group study. ( 21310472 )
2011
6
Genetic variation in the LMP/TAP gene and outcomes of hepatitis B virus infection in the Chinese population. ( 20525414 )
2011
7
No association of TAP and LMP genetic polymorphism in human brucellosis and its complications. ( 20470844 )
2010
8
Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells. ( 18046553 )
2008
9
Potential involvement of the interaction between insulin-like growth factor binding protein (IGFBP)-6 and LIM mineralization protein (LMP)-1 in regulating osteoblast differentiation. ( 18395833 )
2008
10
Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in differential diagnosis between low malignant potential (LMP) and malignant ovarian tumours. ( 17695443 )
2007
11
Low-molecular-weight protein (LMP)2/LMP7 abnormality underlies the downregulation of human leukocyte antigen class I antigen in a hepatocellular carcinoma cell line. ( 17608862 )
2007
12
Identification of the WW domain-interaction sites in the unstructured N-terminal domain of EBV LMP 2A. ( 17174309 )
2007
13
Involvement of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP)-1 in the potentiation of C epsilon mRNA expression in human tonsil-derived cells. ( 17089136 )
2007
14
Lethal multiple pterygium syndrome associated with omphalocele. ( 18286827 )
2007
15
Genetic polymorphisms of LMP/TAP gene and hepatitis B virus infection risk in the Chinese population. ( 17525827 )
2007
16
Strong associations of psoriasis with antigen processing LMP and transport genes TAP differ by gender and phenotype. ( 17581627 )
2007
17
First trimester ultrasound diagnosis of lethal multiple pterygium syndrome. ( 16912497 )
2006
18
Expression of proteasome subunits low molecular mass polypeptide (LMP) 2 and LMP7 in the endometrium and placenta of rhesus monkey (Macaca mulatta) during early pregnancy. ( 15201202 )
2004
19
Association study of LMP gene polymorphisms in Mexican patients with spondyloarthritis. ( 15603870 )
2004
20
Semiquantitative mRNA measurements of osteoinductive growth factors in human iliac-crest bone: expression of LMP splice variants in human bone. ( 12958694 )
2003
21
Recruitment of heterogeneous nuclear ribonucleoprotein A1 in vivo to the LMP/TAP region of the major histocompatibility complex. ( 12435746 )
2003
22
Genes of the LMP/TAP cluster are associated with the human autoimmune disease vitiligo. ( 14551602 )
2003
23
Age dependent impact of LMP polymorphisms on TNFalpha-induced apoptosis in human peripheral blood mononuclear cells. ( 11772516 )
2002
24
Distribution of HLA-A, B alleles and polymorphisms of TAP and LMP genes in Korean patients with atopic dermatitis. ( 11737038 )
2001
25
Polymorphisms of TAP, LMP and HLA-DM genes in the Chinese. ( 11775239 )
2000
26
Characterization of LMP polymorphism in homozygous typing cells and a random population. ( 10027782 )
1999
27
Osteopontin expression in ovarian carcinomas and tumors of low malignant potential (LMP). ( 9824103 )
1998
28
Establishment of long-term in vitro cultures of human ovarian cystadenomas and LMP tumors and examination of their spectrum of expression of matrix-degrading proteinases. ( 9441775 )
1997
29
Analysis of the MHC class I antigen presentation machinery in human embryonal carcinomas: evidence for deficiencies in TAP, LMP and MHC class I expression and their upregulation by IFN-gamma. ( 9420627 )
1997
30
Linkage disequilibrium between HLA class II (DR, DQ, DP) and antigen processing (LMP, TAP, DM) genes of the major histocompatibility complex. ( 8883297 )
1996
31
LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12. ( 8627162 )
1996
32
Genetic polymorphisms of the major histocompatibility complex-encoded antigen-processing genes TAP and LMP in sarcoidosis. ( 8882407 )
1996
33
Gastric lymphoepithelioma-like carcinoma and jejunal B-cell MALT lymphoma with large cell transformation. Demonstration of EBV with identical LMP gene deletions in the carcinoma and large cell lymphoma. ( 8623763 )
1996
34
Reduced membrane major histocompatibility complex class I density and stability in a subset of human renal cell carcinomas with low TAP and LMP expression. ( 9816317 )
1996
35
Polymorphism of antigen processing (TAP, LMP) and HLA class II genes in celiac disease. ( 8045794 )
1994
36
Absence of association of TAP and LMP genes with type 1 (insulin-dependent) diabetes mellitus. ( 7911550 )
1994
37
Proteasome components with reciprocal expression to that of the MHC- encoded LMP proteins. ( 7820546 )
1994
38
Displacement of housekeeping proteasome subunits by MHC-encoded LMPs: a newly discovered mechanism for modulating the multicatalytic proteinase complex. ( 8045254 )
1994
39
Decreased expression of E-cadherin and increased invasive capacity in EBV-LMP-transfected human epithelial and murine adenocarcinoma cells. ( 1330938 )
1992
40
The Epstein-Barr virus encoded membrane protein (LMP) induces phenotypic changes in epithelial cells. ( 1352076 )
1992
41
Homology of proteasome subunits to a major histocompatibility complex-linked LMP gene. ( 1681432 )
1991
42
Lethal multiple pterygium syndrome: report of a new case with hydranencephaly. ( 3789017 )
1986

Variations for Multiple Pterygium Syndrome, Lethal Type

UniProtKB/Swiss-Prot genetic disease variations for Multiple Pterygium Syndrome, Lethal Type:

71
# Symbol AA change Variation ID SNP ID
1 CHRNA1 p.Arg254Leu VAR_043904 rs137852809
2 CHRND p.Phe95Leu VAR_043905 rs121909506
3 CHRNG p.Val107Gly VAR_030753 rs267606726
4 CHRNG p.Arg239Cys VAR_030755 rs121912670

ClinVar genetic disease variations for Multiple Pterygium Syndrome, Lethal Type:

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 CHRNG NM_005199.4(CHRNG): c.715C> T (p.Arg239Cys) single nucleotide variant Pathogenic rs121912670 GRCh37 Chromosome 2, 233407702: 233407702
2 CHRNG NM_005199.4(CHRNG): c.320T> G (p.Val107Gly) single nucleotide variant Pathogenic rs267606726 GRCh37 Chromosome 2, 233405391: 233405391
3 CHRNG NM_005199.4(CHRNG): c.753_754delCT (p.Val253Alafs) deletion Pathogenic rs767503038 GRCh37 Chromosome 2, 233407740: 233407741
4 CHRND NM_000751.2(CHRND): c.234G> A (p.Trp78Ter) single nucleotide variant Pathogenic rs121909505 GRCh37 Chromosome 2, 233392146: 233392146
5 CHRND NM_000751.2(CHRND): c.283T> C (p.Phe95Leu) single nucleotide variant Pathogenic rs121909506 GRCh37 Chromosome 2, 233393011: 233393011
6 CHRND NM_000751.2(CHRND): c.1390C> T (p.Arg464Ter) single nucleotide variant Pathogenic rs121909507 GRCh37 Chromosome 2, 233399858: 233399858
7 CHRNA1 NM_000079.3(CHRNA1): c.517G> A (p.Gly173Ser) single nucleotide variant Pathogenic rs137852801 GRCh37 Chromosome 2, 175618970: 175618970
8 CHRNA1 NM_001039523.2(CHRNA1): c.761G> T (p.Arg254Leu) single nucleotide variant Pathogenic rs137852809 GRCh37 Chromosome 2, 175618323: 175618323
9 CHRNA1 CHRNA1, 17-BP DUP, NT117 duplication Pathogenic
10 CHRNG CHRNG, 1-BP DUP, 459A duplication Pathogenic
11 CHRND NM_000751.2(CHRND): c.1374_1375delGA (p.Lys459Argfs) deletion Likely pathogenic rs1060499782 GRCh38 Chromosome 2, 232535132: 232535133
12 CHRNA1 NM_000079.3(CHRNA1): c.1321G> A (p.Gly441Arg) single nucleotide variant Likely pathogenic rs768407867 GRCh37 Chromosome 2, 175612905: 175612905
13 CHRNA1 NC_000002.12: g.(?_174747592)_(174754414_?)del deletion Pathogenic GRCh38 Chromosome 2, 174747592: 174754414
14 CHRNG NM_005199.4(CHRNG): c.1210C> T (p.Gln404Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 2, 233409251: 233409251

Expression for Multiple Pterygium Syndrome, Lethal Type

Search GEO for disease gene expression data for Multiple Pterygium Syndrome, Lethal Type.

Pathways for Multiple Pterygium Syndrome, Lethal Type

GO Terms for Multiple Pterygium Syndrome, Lethal Type

Cellular components related to Multiple Pterygium Syndrome, Lethal Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 9.56 CHRNA1 CHRND CHRNG RAPSN
2 synapse GO:0045202 9.46 CHRNA1 CHRND CHRNG RAPSN
3 neuromuscular junction GO:0031594 9.32 CHRNA1 RAPSN
4 postsynaptic membrane GO:0045211 9.26 CHRNA1 CHRND CHRNG RAPSN
5 acetylcholine-gated channel complex GO:0005892 8.8 CHRNA1 CHRND CHRNG

Biological processes related to Multiple Pterygium Syndrome, Lethal Type according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.87 CHRNA1 CHRND CHRNG RYR1
2 ion transport GO:0006811 9.76 CHRNA1 CHRND CHRNG RYR1
3 transmembrane transport GO:0055085 9.73 CHRNA1 CHRND RYR1
4 ion transmembrane transport GO:0034220 9.69 CHRNA1 CHRND RYR1
5 muscle contraction GO:0006936 9.61 CHRND CHRNG RYR1
6 excitatory postsynaptic potential GO:0060079 9.58 CHRNA1 CHRND CHRNG
7 regulation of membrane potential GO:0042391 9.55 CHRNA1 CHRND
8 cation transmembrane transport GO:0098655 9.54 CHRND CHRNG
9 cation transport GO:0006812 9.52 CHRNA1 CHRND
10 neuromuscular process GO:0050905 9.49 CHRNA1 CHRND
11 skeletal muscle contraction GO:0003009 9.48 CHRNA1 CHRND
12 regulation of postsynaptic membrane potential GO:0060078 9.43 CHRNA1 CHRND CHRNG
13 musculoskeletal movement GO:0050881 9.37 CHRNA1 CHRND
14 response to nicotine GO:0035094 9.33 CHRNA1 CHRND CHRNG
15 skeletal muscle tissue growth GO:0048630 9.32 CHRNA1 CHRND
16 neuromuscular synaptic transmission GO:0007274 9.13 CHRNA1 CHRND CHRNG
17 synaptic transmission, cholinergic GO:0007271 8.92 CHRNA1 CHRND CHRNG RAPSN

Molecular functions related to Multiple Pterygium Syndrome, Lethal Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.5 CHRNA1 CHRND RYR1
2 extracellular ligand-gated ion channel activity GO:0005230 9.43 CHRNA1 CHRND CHRNG
3 acetylcholine receptor activity GO:0015464 9.37 CHRNA1 CHRNG
4 ligand-gated ion channel activity GO:0015276 9.33 CHRNA1 CHRND CHRNG
5 acetylcholine binding GO:0042166 9.13 CHRNA1 CHRND CHRNG
6 acetylcholine-gated cation-selective channel activity GO:0022848 8.8 CHRNA1 CHRND CHRNG

Sources for Multiple Pterygium Syndrome, Lethal Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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