LCCS1
MCID: LTH007
MIFTS: 37

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 75 29 13 6 44 15 73
Multiple Contracture Syndrome, Finnish Type 57 12 53 59
Lccs1 57 12 59 75
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 75
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:
Mortality/Aging neonatal death
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 253310
Disease Ontology 12 DOID:0060559
Orphanet 59 ORPHA1486
MESH via Orphanet 45 C537194
UMLS via Orphanet 74 C1854664
ICD10 via Orphanet 34 Q68.8
MedGen 42 C1854664
UMLS 73 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: 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 lethal arthrogryposis with anterior horn cell disease. An important gene associated with Lethal Congenital Contracture Syndrome 1 is GLE1 (GLE1, RNA Export Mediator). The drugs Indapamide 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 neck

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 : 75 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 32)
# Related Disease Score Top Affiliating Genes
1 lethal congenital contracture syndrome 33.0 PIP5K1C GLE1 ERBB3
2 lethal arthrogryposis with anterior horn cell disease 32.1 LOC101929270 GLE1
3 anterior horn cell disease 29.1 TARDBP SON LOC101929270 GLE1 FUS
4 leukoencephalopathy, brain calcifications, and cysts 11.7
5 leukoencephalopathy, cerebral calcifications, and cysts 11.5
6 hepatocellular carcinoma 11.3
7 lung large cell carcinoma 11.2
8 cerebroretinal microangiopathy with calcifications and cysts 1 11.1
9 lethal congenital contracture syndrome 3 11.0
10 lethal congenital contracture syndrome 7 11.0
11 lethal congenital contracture syndrome 8 11.0
12 leber congenital amaurosis 10.2
13 neurogenic bladder 10.1 PIP5K1C ERBB3
14 lung cancer 10.0
15 congenital contractures 10.0
16 lethal congenital contracture syndrome 2 10.0 PIP5K1C GLE1 ERBB3
17 alexia 9.9 TARDBP MBP
18 clear cell sarcoma 9.9 FUS ERBB3
19 expressive language disorder 9.9 TARDBP FUS
20 amyotrophic lateral sclerosis type 6 9.9 TARDBP FUS
21 amyotrophic lateral sclerosis 18 9.9 TARDBP FUS
22 agraphia 9.9 TARDBP MBP
23 amyotrophic lateral sclerosis type 14 9.9 TARDBP FUS
24 amyotrophic lateral sclerosis 21 9.8 TARDBP FUS
25 amyotrophic lateral sclerosis 11 9.8 TARDBP FUS
26 amyotrophic lateral sclerosis 7 9.8 TARDBP FUS
27 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 9.8 TARDBP FUS
28 amyotrophic lateral sclerosis 9 9.8 TARDBP FUS
29 spinocerebellar ataxia 31 9.8 TARDBP FUS
30 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 9.8 TARDBP FUS
31 amyotrophic lateral sclerosis 1 9.7 TARDBP GLE1 FUS
32 pick disease of brain 9.6 TARDBP 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

Symptoms via clinical synopsis from OMIM:

57
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

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 neck 59 32 frequent (33%) Frequent (79-30%) HP:0000470
3 abnormal cortical bone morphology 59 32 frequent (33%) Frequent (79-30%) HP:0003103
4 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
5 skeletal muscle atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0003202
6 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
7 limitation of joint mobility 59 32 frequent (33%) Frequent (79-30%) HP:0001376
8 abnormal form of the vertebral bodies 59 32 occasional (7.5%) Occasional (29-5%) HP:0003312
9 abnormality of the hip bone 59 32 hallmark (90%) Very frequent (99-80%) HP:0003272
10 webbed neck 59 32 frequent (33%) Frequent (79-30%) HP:0000465
11 low-set, posteriorly rotated ears 59 32 frequent (33%) Frequent (79-30%) HP:0000368
12 polyhydramnios 59 32 frequent (33%) Frequent (79-30%) HP:0001561
13 abnormality of the ribs 59 32 frequent (33%) Frequent (79-30%) HP:0000772
14 recurrent fractures 59 32 frequent (33%) Frequent (79-30%) HP:0002757
15 abnormality of the elbow 59 32 frequent (33%) Frequent (79-30%) HP:0009811
16 pulmonary hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002089
17 slender long bone 59 32 frequent (33%) Frequent (79-30%) HP:0003100
18 amniotic constriction ring 59 32 frequent (33%) Frequent (79-30%) HP:0009775
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 paucity of anterior horn motor neurons 32 HP:0007277
25 widening of cervical spinal canal 32 HP:0004571

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

26 (show all 34)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-109 9.85 GLE1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.85 PIP5K1C
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 9.85 ERBB3
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.85 PIP5K1C
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.85 ERBB3
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.85 GLE1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.85 ERBB3 GLE1 PIP5K1C
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.85 ERBB3
9 Decreased viability GR00106-A-0 9.73 ERBB3
10 Decreased viability GR00221-A-2 9.73 ERBB3 PIP5K1C
11 Decreased viability GR00221-A-4 9.73 ERBB3 FUS PIP5K1C
12 Decreased viability GR00301-A 9.73 ERBB3
13 Decreased viability GR00342-S-2 9.73 ERBB3
14 Decreased viability GR00342-S-3 9.73 ERBB3
15 Decreased viability GR00402-S-2 9.73 ERBB3 FUS PIP5K1C
16 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.66 PIP5K1C
17 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.66 ERBB3
18 Increased shRNA abundance (Z-score > 2) GR00366-A-130 9.66 PIP5K1C
19 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.66 GLE1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-159 9.66 SON
21 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.66 ERBB3
22 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.66 SON
23 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.66 PIP5K1C
24 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.66 PIP5K1C
25 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.66 GLE1
26 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.66 PIP5K1C
27 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.66 ERBB3
28 Increased shRNA abundance (Z-score > 2) GR00366-A-30 9.66 SON
29 Increased shRNA abundance (Z-score > 2) GR00366-A-31 9.66 GLE1
30 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.66 PIP5K1C
31 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.66 PIP5K1C
32 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.66 SON
33 Increased shRNA abundance (Z-score > 2) GR00366-A-69 9.66 PIP5K1C
34 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.66 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
Indapamide Approved 26807-65-8 3702
2
Perindopril Approved 107133-36-8, 82834-16-0 107807
3
Gliclazide Approved 21187-98-4 3475
4 Hypoglycemic Agents
5 Antihypertensive 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 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, Lung, Brain

Publications for Lethal Congenital Contracture Syndrome 1

Articles related to Lethal Congenital Contracture Syndrome 1:

# Title Authors Year
1
A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization. ( 22357925 )
2012

Variations for Lethal Congenital Contracture Syndrome 1

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

75
# 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 ERBB3 NM_001982.3(ERBB3): c.3565_3567delGAA (p.Glu1191del) deletion Uncertain significance rs780883720 GRCh37 Chromosome 12, 56495375: 56495377
6 ERBB3 NM_001982.3(ERBB3): c.3565_3567delGAA (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

Molecular functions related to Lethal Congenital Contracture Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 8.92 ERBB3 FUS GLE1 TARDBP

Sources for Lethal Congenital Contracture Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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