LCCS1
MCID: LTH007
MIFTS: 41

Lethal Congenital Contracture Syndrome 1 (LCCS1)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Lethal Congenital Contracture Syndrome 1

MalaCards integrated aliases for Lethal Congenital Contracture Syndrome 1:

Name: Lethal Congenital Contracture Syndrome 1 58 12 54 76 30 13 6 45 15 74
Multiple Contracture Syndrome, Finnish Type 58 12 54 60
Lccs1 58 12 60 76
Lethal Autosomal Recessive Syndrome of Multiple Congenital Contractures 54
Contracture Syndrome, Lethal, Congenital, Type 1 41
Lethal Congenital Contracture Syndrome Type 1 60
Multiple Contracture Syndrome Finnish Type 76
Herva Disease 60
Lccs 58

Characteristics:

Orphanet epidemiological data:

60
lethal congenital contracture syndrome type 1
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: infantile;

OMIM:

58
Miscellaneous:
neonatal death

Inheritance:
autosomal recessive


HPO:

33
lethal congenital contracture syndrome 1:
Clinical modifier neonatal death
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0060559
OMIM 58 253310
MESH via Orphanet 46 C537194
ICD10 via Orphanet 35 Q68.8
UMLS via Orphanet 75 C1854664
Orphanet 60 ORPHA1486
MedGen 43 C1854664
UMLS 74 C1854664

Summaries for Lethal Congenital Contracture Syndrome 1

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1486Disease definitionLethal congenitalcontracturesyndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.Visit the Orphanet disease page for more resources.

MalaCards based summary : Lethal Congenital Contracture Syndrome 1, also known as multiple contracture syndrome, finnish type, is related to lethal congenital contracture syndrome and anterior horn cell disease. An important gene associated with Lethal Congenital Contracture Syndrome 1 is GLE1 (GLE1 RNA Export Mediator). The drugs Gliclazide and Perindopril have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, bone and spinal cord, and related phenotypes are hypertelorism and short stature

Disease Ontology : 12 A lethal congenital contracture syndrome that has material basis in homozygous or compound heterozygous mutation in the mRNA export mediator GLE1 on chromosome 9q34.

OMIM : 58 Autosomal recessive lethal congenital contracture syndrome (LCCS) is the most severe, neonatally lethal, form of arthrogryposis (see 108120), a disorder characterized by congenital nonprogressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth (summary by Markus et al., 2012). (253310)

UniProtKB/Swiss-Prot : 76 Lethal congenital contracture syndrome 1: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non- progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS1 patients manifest early fetal hydrops and akinesia, micrognathia, pulmonary hypoplasia, pterygia, and multiple joint contractures. It leads to prenatal death.

Related Diseases for Lethal Congenital Contracture Syndrome 1

Diseases in the Lethal Congenital Contracture Syndrome family:

Lethal Congenital Contracture Syndrome 1 Lethal Congenital Contracture Syndrome 2
Lethal Congenital Contracture Syndrome 3 Lethal Congenital Contracture Syndrome 4
Lethal Congenital Contracture Syndrome 5 Lethal Congenital Contracture Syndrome 6
Lethal Congenital Contracture Syndrome 7 Lethal Congenital Contracture Syndrome 8
Lethal Congenital Contracture Syndrome 9 Lethal Congenital Contracture Syndrome 10
Lethal Congenital Contracture Syndrome 11

Diseases related to Lethal Congenital Contracture Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 19)
# Related Disease Score Top Affiliating Genes
1 lethal congenital contracture syndrome 32.8 ERBB3 GLE1 PIP5K1C
2 anterior horn cell disease 28.8 FUS GLE1 LOC101929270 SON
3 leukoencephalopathy, brain calcifications, and cysts 12.0
4 leukoencephalopathy, cerebral calcifications, and cysts 11.5
5 hepatocellular carcinoma 11.3
6 congenital arthrogryposis with anterior horn cell disease 11.3
7 lung large cell carcinoma 11.3
8 cerebroretinal microangiopathy with calcifications and cysts 1 11.1
9 lethal congenital contracture syndrome 3 11.1
10 lethal congenital contracture syndrome 7 11.1
11 lethal congenital contracture syndrome 8 11.1
12 leber congenital amaurosis 10.2
13 lung cancer 10.0
14 spinal muscular atrophy 10.0
15 proximal spinal muscular atrophy 10.0
16 congenital contractures 10.0
17 neurogenic bladder 9.9 ERBB3 PIP5K1C
18 lethal congenital contracture syndrome 2 9.7 ERBB3 GLE1 PIP5K1C
19 clear cell sarcoma 9.6 ERBB3 FUS

Graphical network of the top 20 diseases related to Lethal Congenital Contracture Syndrome 1:



Diseases related to Lethal Congenital Contracture Syndrome 1

Symptoms & Phenotypes for Lethal Congenital Contracture Syndrome 1

Human phenotypes related to Lethal Congenital Contracture Syndrome 1:

60 33 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 60 33 hallmark (90%) Very frequent (99-80%) HP:0000316
2 short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0004322
3 skeletal muscle atrophy 60 33 hallmark (90%) Very frequent (99-80%) HP:0003202
4 micrognathia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000347
5 abnormality of the hip bone 60 33 hallmark (90%) Very frequent (99-80%) HP:0003272
6 pulmonary hypoplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002089
7 short neck 60 33 frequent (33%) Frequent (79-30%) HP:0000470
8 abnormal cortical bone morphology 60 33 frequent (33%) Frequent (79-30%) HP:0003103
9 limitation of joint mobility 60 33 frequent (33%) Frequent (79-30%) HP:0001376
10 webbed neck 60 33 frequent (33%) Frequent (79-30%) HP:0000465
11 low-set, posteriorly rotated ears 60 33 frequent (33%) Frequent (79-30%) HP:0000368
12 polyhydramnios 60 33 frequent (33%) Frequent (79-30%) HP:0001561
13 abnormality of the ribs 60 33 frequent (33%) Frequent (79-30%) HP:0000772
14 recurrent fractures 60 33 frequent (33%) Frequent (79-30%) HP:0002757
15 abnormality of the elbow 60 33 frequent (33%) Frequent (79-30%) HP:0009811
16 slender long bone 60 33 frequent (33%) Frequent (79-30%) HP:0003100
17 amniotic constriction ring 60 33 frequent (33%) Frequent (79-30%) HP:0009775
18 abnormal form of the vertebral bodies 60 33 occasional (7.5%) Occasional (29-5%) HP:0003312
19 edema 33 HP:0000969
20 abnormality of the thorax 33 HP:0000765
21 arthrogryposis multiplex congenita 33 HP:0002804
22 hypoplasia of the musculature 33 HP:0009004
23 abnormality of the amniotic fluid 33 HP:0001560
24 paucity of anterior horn motor neurons 33 HP:0007277
25 widening of cervical spinal canal 33 HP:0004571

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Face:
micrognathia

Muscle Soft Tissue:
muscle atrophy
muscle hypoplasia

Skeletal Limbs:
multiple congenital contractures
generalized thinning of tubular bones

Prenatal Manifestations Amniotic Fluid:
marked fetal hydrops

Respiratory Lung:
pulmonary hypoplasia

Chest Ribs Sternum Clavicles And Scapulae:
thin fishbone-like ribs

Neurologic Central Nervous System:
paucity of anterior horn motor neurons

Clinical features from OMIM:

253310

GenomeRNAi Phenotypes related to Lethal Congenital Contracture Syndrome 1 according to GeneCards Suite gene sharing:

27 (show all 34)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-109 9.81 GLE1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.81 PIP5K1C
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.81 PIP5K1C
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.81 ERBB3
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.81 GLE1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.81 ERBB3 GLE1 PIP5K1C
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.81 ERBB3
8 Decreased viability GR00106-A-0 9.73 ERBB3
9 Decreased viability GR00221-A-2 9.73 ERBB3 PIP5K1C
10 Decreased viability GR00221-A-4 9.73 ERBB3 FUS PIP5K1C
11 Decreased viability GR00301-A 9.73 ERBB3
12 Decreased viability GR00342-S-2 9.73 ERBB3
13 Decreased viability GR00342-S-3 9.73 ERBB3
14 Decreased viability GR00402-S-2 9.73 ERBB3 FUS PIP5K1C
15 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.68 PIP5K1C
16 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.68 ERBB3
17 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.68 ERBB3
18 Increased shRNA abundance (Z-score > 2) GR00366-A-130 9.68 PIP5K1C
19 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.68 GLE1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-159 9.68 SON
21 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.68 ERBB3
22 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.68 SON
23 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.68 PIP5K1C
24 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.68 PIP5K1C
25 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.68 GLE1
26 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.68 PIP5K1C
27 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.68 ERBB3
28 Increased shRNA abundance (Z-score > 2) GR00366-A-30 9.68 SON
29 Increased shRNA abundance (Z-score > 2) GR00366-A-31 9.68 GLE1
30 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.68 PIP5K1C
31 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.68 PIP5K1C
32 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.68 SON
33 Increased shRNA abundance (Z-score > 2) GR00366-A-69 9.68 PIP5K1C
34 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.68 ERBB3 GLE1 PIP5K1C SON

Drugs & Therapeutics for Lethal Congenital Contracture Syndrome 1

Drugs for Lethal Congenital Contracture Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Gliclazide Approved 21187-98-4 3475
2
Perindopril Approved 107133-36-8, 82834-16-0 107807
3
Indapamide Approved 26807-65-8 3702
4 Antihypertensive Agents
5 Hypoglycemic Agents
6 Indapamide, perindopril drug combination

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Action in Diabetes and Vascular Disease Preterax and Diamicron MR Controlled Evaluation Post Trial Observational Study Completed NCT00949286
2 Study of Families With Melanoma Recruiting NCT00445783
3 Surefire Catheter Versus Standard End-hole Microcatheter: A Pilot Study Suspended NCT02446925 Not Applicable

Search NIH Clinical Center for Lethal Congenital Contracture Syndrome 1

Cochrane evidence based reviews: lethal congenital contracture syndrome 1

Genetic Tests for Lethal Congenital Contracture Syndrome 1

Genetic tests related to Lethal Congenital Contracture Syndrome 1:

# Genetic test Affiliating Genes
1 Lethal Congenital Contracture Syndrome 1 30 GLE1

Anatomical Context for Lethal Congenital Contracture Syndrome 1

MalaCards organs/tissues related to Lethal Congenital Contracture Syndrome 1:

42
Skeletal Muscle, Bone, Spinal Cord, Lung, Brain

Publications for Lethal Congenital Contracture Syndrome 1

Articles related to Lethal Congenital Contracture Syndrome 1:

# Title Authors Year
1
Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1. ( 28884921 )
2017
2
Gle1 functions during mRNA export in an oligomeric complex that is altered in human disease. ( 24243016 )
2013
3
A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization. ( 22357925 )
2012
4
Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. ( 18204449 )
2008

Variations for Lethal Congenital Contracture Syndrome 1

UniProtKB/Swiss-Prot genetic disease variations for Lethal Congenital Contracture Syndrome 1:

76
# Symbol AA change Variation ID SNP ID
1 GLE1 p.Arg569His VAR_043875 rs121434407

ClinVar genetic disease variations for Lethal Congenital Contracture Syndrome 1:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 GLE1 NM_001003722.1(GLE1): c.433-10A> G single nucleotide variant Pathogenic rs386833693 GRCh37 Chromosome 9, 131284937: 131284937
2 GLE1 NM_001003722.1(GLE1): c.433-10A> G single nucleotide variant Pathogenic rs386833693 GRCh38 Chromosome 9, 128522658: 128522658
3 GLE1 NM_001003722.1(GLE1): c.1706G> A (p.Arg569His) single nucleotide variant Likely pathogenic rs121434407 GRCh37 Chromosome 9, 131298693: 131298693
4 GLE1 NM_001003722.1(GLE1): c.1706G> A (p.Arg569His) single nucleotide variant Likely pathogenic rs121434407 GRCh38 Chromosome 9, 128536414: 128536414
5 GLE1 NM_001003722.1(GLE1): c.5C> G (p.Pro2Arg) single nucleotide variant Uncertain significance rs150246404 GRCh37 Chromosome 9, 131267089: 131267089
6 GLE1 NM_001003722.1(GLE1): c.5C> G (p.Pro2Arg) single nucleotide variant Uncertain significance rs150246404 GRCh38 Chromosome 9, 128504810: 128504810
7 ERBB3 NM_001982.3(ERBB3): c.3565_3567del (p.Glu1191del) deletion Uncertain significance rs780883720 GRCh37 Chromosome 12, 56495375: 56495377
8 ERBB3 NM_001982.3(ERBB3): c.3565_3567del (p.Glu1191del) deletion Uncertain significance rs780883720 GRCh38 Chromosome 12, 56101591: 56101593

Expression for Lethal Congenital Contracture Syndrome 1

Search GEO for disease gene expression data for Lethal Congenital Contracture Syndrome 1.

Pathways for Lethal Congenital Contracture Syndrome 1

GO Terms for Lethal Congenital Contracture Syndrome 1

Biological processes related to Lethal Congenital Contracture Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane organization GO:0061024 8.96 MBP PIP5K1C
2 phosphatidylinositol phosphorylation GO:0046854 8.32 PIP5K1C

Sources for Lethal Congenital Contracture Syndrome 1

3 CDC
7 CNVD
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10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
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31 HGMD
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35 ICD10 via Orphanet
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58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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