LCCS1
MCID: LTH007
MIFTS: 42

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 57 12 53 74 29 13 6 44 15 72
Multiple Contracture Syndrome, Finnish Type 57 12 53 59
Lccs1 57 12 59 74
Lethal Autosomal Recessive Syndrome of Multiple Congenital Contractures 53
Contracture Syndrome, Lethal, Congenital, Type 1 40
Lethal Congenital Contracture Syndrome Type 1 59
Multiple Contracture Syndrome Finnish Type 74
Herva Disease 59
Lccs 57

Characteristics:

Orphanet epidemiological data:

59
lethal congenital contracture syndrome type 1
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: infantile;

OMIM:

57
Miscellaneous:
neonatal death

Inheritance:
autosomal recessive


HPO:

32
lethal congenital contracture syndrome 1:
Clinical modifier neonatal death
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0060559
MESH via Orphanet 45 C537194
ICD10 via Orphanet 34 Q68.8
UMLS via Orphanet 73 C1854664
Orphanet 59 ORPHA1486
MedGen 42 C1854664
UMLS 72 C1854664

Summaries for Lethal Congenital Contracture Syndrome 1

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1486DefinitionLethal congenital contracture syndrome 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 Calcium carbonate and Calcium 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 : 57 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 : 74 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 27)
# Related Disease Score Top Affiliating Genes
1 lethal congenital contracture syndrome 32.7 PIP5K1C GLE1 ERBB3
2 anterior horn cell disease 28.1 SON LOC101929270 GLE1 FUS
3 leukoencephalopathy, brain calcifications, and cysts 11.9
4 leukoencephalopathy with calcifications and cysts 11.5
5 cerebroretinal microangiopathy with calcifications and cysts 1 11.5
6 hepatocellular carcinoma 11.4
7 congenital arthrogryposis with anterior horn cell disease 11.4
8 lung large cell carcinoma 11.4
9 lethal congenital contracture syndrome 3 11.2
10 lethal congenital contracture syndrome 7 11.2
11 lethal congenital contracture syndrome 8 11.2
12 leukoencephalopathy, cerebral calcifications, and cysts 11.2
13 lung cancer 10.3
14 branchiootic syndrome 1 10.1
15 lung cancer susceptibility 3 10.1
16 alkuraya-kucinskas syndrome 10.1
17 distal arthrogryposis 10.1
18 spinal muscular atrophy 10.1
19 squamous cell carcinoma 10.1
20 lung benign neoplasm 10.1
21 compartment syndrome 10.1
22 muscular atrophy 10.1
23 congenital amyoplasia 10.1
24 congenital contractures 10.0
25 neurogenic bladder 9.8 PIP5K1C ERBB3
26 lethal congenital contracture syndrome 2 9.5 PIP5K1C GLE1 ERBB3
27 clear cell sarcoma 9.3 FUS ERBB3

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:

59 32 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000316
2 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
3 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
4 skeletal muscle atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0003202
5 abnormality of the hip bone 59 32 hallmark (90%) Very frequent (99-80%) HP:0003272
6 pulmonary hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002089
7 short neck 59 32 frequent (33%) Frequent (79-30%) HP:0000470
8 abnormal cortical bone morphology 59 32 frequent (33%) Frequent (79-30%) HP:0003103
9 limitation of joint mobility 59 32 frequent (33%) Frequent (79-30%) HP:0001376
10 webbed neck 59 32 frequent (33%) Frequent (79-30%) HP:0000465
11 slender long bone 59 32 frequent (33%) Frequent (79-30%) HP:0003100
12 low-set, posteriorly rotated ears 59 32 frequent (33%) Frequent (79-30%) HP:0000368
13 polyhydramnios 59 32 frequent (33%) Frequent (79-30%) HP:0001561
14 abnormality of the ribs 59 32 frequent (33%) Frequent (79-30%) HP:0000772
15 recurrent fractures 59 32 frequent (33%) Frequent (79-30%) HP:0002757
16 abnormality of the elbow 59 32 frequent (33%) Frequent (79-30%) HP:0009811
17 amniotic constriction ring 59 32 frequent (33%) Frequent (79-30%) HP:0009775
18 abnormal form of the vertebral bodies 59 32 occasional (7.5%) Occasional (29-5%) HP:0003312
19 edema 32 HP:0000969
20 abnormality of the thorax 32 HP:0000765
21 arthrogryposis multiplex congenita 32 HP:0002804
22 hypoplasia of the musculature 32 HP:0009004
23 abnormality of the amniotic fluid 32 HP:0001560
24 widening of cervical spinal canal 32 HP:0004571
25 paucity of anterior horn motor neurons 32 HP:0007277

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Face:
micrognathia

Neurologic Central Nervous System:
paucity of anterior horn motor neurons

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

Prenatal Manifestations Amniotic Fluid:
marked fetal hydrops

Respiratory Lung:
pulmonary hypoplasia

Muscle Soft Tissue:
muscle atrophy
muscle hypoplasia

Skeletal Limbs:
multiple congenital contractures
generalized thinning of tubular bones

Clinical features from OMIM:

253310

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00106-A-0 9.4 ERBB3
2 Decreased viability GR00221-A-2 9.4 ERBB3 PIP5K1C
3 Decreased viability GR00221-A-4 9.4 ERBB3 FUS PIP5K1C
4 Decreased viability GR00301-A 9.4 ERBB3
5 Decreased viability GR00342-S-2 9.4 ERBB3
6 Decreased viability GR00342-S-3 9.4 ERBB3
7 Decreased viability GR00402-S-2 9.4 ERBB3 FUS PIP5K1C

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 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Calcium carbonate Approved, Investigational Phase 1 471-34-1
2
Calcium Approved, Nutraceutical Phase 1 7440-70-2 271
3 Gastrointestinal Agents Phase 1
4 Antacids Phase 1
5 Hormones Phase 1
6 Anti-Ulcer Agents Phase 1
7 Calcium, Dietary Phase 1
8 Calcium Supplement Phase 1
9 Bone Density Conservation Agents Phase 1
10
Menthol Approved 2216-51-5 16666
11 Dermatologic Agents
12 Antipruritics

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Human Crossover Study to Compare the Bioavailability of Calcium From AlgaeCal® Versus a Proprietary Calcium Dietary Supplement Completed NCT01609413 Phase 1
2 Addictive Potential of Little Cigars/Cigarillos in Dual Users: Effect by Flavor and Gender Recruiting NCT03496077
3 Assessing Tobacco Product Choice When the Cost of Menthol Cigarettes Increases Recruiting NCT03612349

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 29 GLE1

Anatomical Context for Lethal Congenital Contracture Syndrome 1

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

41
Skeletal Muscle, Bone, Spinal Cord

Publications for Lethal Congenital Contracture Syndrome 1

Articles related to Lethal Congenital Contracture Syndrome 1:

(show all 17)
# Title Authors PMID Year
1
Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. 38 8 71
18204449 2008
2
Gle1 functions during mRNA export in an oligomeric complex that is altered in human disease. 38 71
24243016 2013
3
Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1. 71
28884921 2017
4
Autosomal recessive lethal congenital contractural syndrome type 4 (LCCS4) caused by a mutation in MYBPC1. 8
22610851 2012
5
Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study. 8
16892327 2006
6
Assignment of the disease locus for lethal congenital contracture syndrome to a restricted region of chromosome 9q34, by genome scan using five affected individuals. 8
9683599 1998
7
Lethal congenital contracture syndrome (LCCS), a fetal anterior horn cell disease, is not linked to the SMA 5q locus. 8
7897624 1995
8
Lethal congenital contracture syndrome: further delineation and genetic aspects. 8
7966188 1994
9
A syndrome of multiple congenital contractures: neuropathological analysis on five fetal cases. 8
3344776 1988
10
A lethal autosomal recessive syndrome of multiple congenital contractures. 8
3993672 1985
11
Multiple ankyloses, facial anomalies, and pulmonary hypoplasia associated with severe antenatal spinal muscular atrophy. 8
6875715 1983
12
A homozygous I684T in GLE1 as a novel cause of arthrogryposis and motor neuron loss. 38
28657126 2018
13
Expansion of the GLE1-associated arthrogryposis multiplex congenita clinical spectrum. 38
27684565 2017
14
Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo. 38
26921650 2016
15
Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis. 38
25343993 2015
16
Insights into mRNA export-linked molecular mechanisms of human disease through a Gle1 structure-function analysis. 38
24275432 2014
17
A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization. 38
22357925 2012

Variations for Lethal Congenital Contracture Syndrome 1

ClinVar genetic disease variations for Lethal Congenital Contracture Syndrome 1:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 GLE1 NM_001499.2(GLE1): c.433-10A> G single nucleotide variant Pathogenic rs386833693 9:131284937-131284937 9:128522658-128522658
2 GLE1 NM_001499.2(GLE1): c.1706G> A (p.Arg569His) single nucleotide variant Likely pathogenic rs121434407 9:131298693-131298693 9:128536414-128536414
3 GLE1 NM_001499.2(GLE1): c.5C> G (p.Pro2Arg) single nucleotide variant Uncertain significance rs150246404 9:131267089-131267089 9:128504810-128504810
4 ERBB3 NM_001982.3(ERBB3): c.3567_3569AGA[2] (p.Glu1191del) short repeat Uncertain significance rs780883720 12:56495375-56495377 12:56101591-56101593

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

74
# Symbol AA change Variation ID SNP ID
1 GLE1 p.Arg569His VAR_043875 rs121434407

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 PIP5K1C MBP
2 phosphatidylinositol phosphorylation GO:0046854 8.32 PIP5K1C

Sources for Lethal Congenital Contracture Syndrome 1

3 CDC
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10 dbSNP
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30 HGMD
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34 ICD10 via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
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73 UMLS via Orphanet
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