MCID: LTH008
MIFTS: 46

Lethal Congenital Contracture Syndrome 2

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

Aliases & Classifications for Lethal Congenital Contracture Syndrome 2

MalaCards integrated aliases for Lethal Congenital Contracture Syndrome 2:

Name: Lethal Congenital Contracture Syndrome 2 57 12 53 75 29 6 44 15 73
Lccs2 57 12 53 59 75
Multiple Contracture Syndrome, Israeli-Bedouin Type 12 59
Lethal Congenital Contractural Syndrome 2 57 13
Multiple Contracture Syndrome, Israeli Bedouin Type a 57
Israeli Bedouin Multiple Contracture Syndrome Type a 75
Multiple Contracture Syndrome, Israeli Bedouin Type 53
Contracture Syndrome, Lethal, Congenital, Type 2 40
Lethal Congenital Contracture Syndrome Type 2 59

Characteristics:

Orphanet epidemiological data:

59
lethal congenital contracture syndrome type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: infantile;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
most affected infants die shortly after birth from respiratory failure


HPO:

32
lethal congenital contracture syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 607598
Disease Ontology 12 DOID:0060560
ICD10 33 Q68.8
Orphanet 59 ORPHA137776
UMLS via Orphanet 74 C1843478
ICD10 via Orphanet 34 Q68.8
MedGen 42 C1843478
UMLS 73 C1843478

Summaries for Lethal Congenital Contracture Syndrome 2

UniProtKB/Swiss-Prot : 75 Lethal congenital contracture syndrome 2: 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. LCCS2 patients manifest craniofacial/ocular findings, lack of hydrops, multiple pterygia, and fractures, as well as a normal duration of pregnancy and a unique feature of a markedly distended urinary bladder (neurogenic bladder defect). The phenotype suggests a spinal cord neuropathic etiology.

MalaCards based summary : Lethal Congenital Contracture Syndrome 2, also known as lccs2, is related to lethal congenital contracture syndrome and lethal congenital contracture syndrome 3. An important gene associated with Lethal Congenital Contracture Syndrome 2 is ERBB3 (Erb-B2 Receptor Tyrosine Kinase 3), and among its related pathways/superpathways are PI3K-Akt signaling pathway and PI3K/AKT activation. The drugs Gliclazide and Indapamide have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, spinal cord and lung, and related phenotypes are skeletal muscle atrophy and micrognathia

Disease Ontology : 12 A lethal congenital contracture syndrome that can be that has material basis in homozygous mutation in the ERBB3 gene on chromosome 12q13.

Description from OMIM: 607598

Related Diseases for Lethal Congenital Contracture Syndrome 2

Graphical network of the top 20 diseases related to Lethal Congenital Contracture Syndrome 2:



Diseases related to Lethal Congenital Contracture Syndrome 2

Symptoms & Phenotypes for Lethal Congenital Contracture Syndrome 2

Symptoms via clinical synopsis from OMIM:

57
Respiratory:
respiratory insufficiency
respiratory failure in infancy

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
no fetal hydrops

Genitourinary Kidneys:
hydronephrosis
cystic changes in the kidney

Skeletal:
arthrogryposis

Respiratory Lung:
normal lung histology

Neurologic Central Nervous System:
neurogenic muscle atrophy, especially in the lower limbs
anterior horn atrophy
spinal cord glial hyperplasia

Head And Neck Face:
micrognathia
hemifacial palsy

Prenatal Manifestations Movement:
decreased fetal movement
akinesia

Cardiovascular Heart:
ventricular septal defect (in some patients)
dilated cardiomyopathy (in some patients)

Head And Neck Eyes:
high myopia
degenerative vitreoretinopathy

Genitourinary Bladder:
distended urinary bladder


Clinical features from OMIM:

607598

Human phenotypes related to Lethal Congenital Contracture Syndrome 2:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 skeletal muscle atrophy 32 HP:0003202
2 micrognathia 32 HP:0000347
3 edema 32 HP:0000969
4 arthrogryposis multiplex congenita 32 HP:0002804
5 respiratory failure 32 HP:0002878
6 polyhydramnios 32 HP:0001561
7 ventricular septal defect 32 occasional (7.5%) HP:0001629
8 decreased fetal movement 32 HP:0001558
9 hydronephrosis 32 HP:0000126
10 dilated cardiomyopathy 32 occasional (7.5%) HP:0001644
11 akinesia 32 HP:0002304
12 high myopia 32 HP:0011003
13 degenerative vitreoretinopathy 32 HP:0007964

GenomeRNAi Phenotypes related to Lethal Congenital Contracture Syndrome 2 according to GeneCards Suite gene sharing:

26 (show all 28)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-109 9.97 GLE1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.97 PIP5K1C
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.97 NTRK1 PIP5K1C
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-20 9.97 NTRK1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.97 ERBB3
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.97 GLE1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.97 ERBB3 GLE1 NTRK1 PIP5K1C
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 9.97 ERBB3 NTRK1
9 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.68 PIP5K1C
10 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.68 ERBB3
11 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.68 ERBB3
12 Increased shRNA abundance (Z-score > 2) GR00366-A-130 9.68 PIP5K1C
13 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.68 GLE1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.68 ERBB3
15 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.68 NTRK1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.68 PIP5K1C
17 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.68 PIP5K1C
18 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.68 GLE1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.68 PIP5K1C
20 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.68 ERBB3
21 Increased shRNA abundance (Z-score > 2) GR00366-A-31 9.68 GLE1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.68 NTRK1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.68 PIP5K1C
24 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.68 NTRK1 PIP5K1C
25 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.68 NTRK1
26 Increased shRNA abundance (Z-score > 2) GR00366-A-69 9.68 PIP5K1C
27 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.68 NTRK1 PIP5K1C ERBB3 GLE1
28 Increased senescence-associated beta-galactosidase protein expression after pRB stimulation GR00230-A-2 8.96 ERBB3 NTRK1

MGI Mouse Phenotypes related to Lethal Congenital Contracture Syndrome 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 9.26 EGF ERBB3 NTRK1 PIP5K1C
2 normal MP:0002873 8.92 EGF ERBB3 NTRK1 PIP5K1C

Drugs & Therapeutics for Lethal Congenital Contracture Syndrome 2

Drugs for Lethal Congenital Contracture Syndrome 2 (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
Indapamide Approved 26807-65-8 3702
3
Perindopril Approved 107133-36-8, 82834-16-0 107807
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

Search NIH Clinical Center for Lethal Congenital Contracture Syndrome 2

Cochrane evidence based reviews: lethal congenital contracture syndrome 2

Genetic Tests for Lethal Congenital Contracture Syndrome 2

Genetic tests related to Lethal Congenital Contracture Syndrome 2:

# Genetic test Affiliating Genes
1 Lethal Congenital Contracture Syndrome 2 29 ERBB3

Anatomical Context for Lethal Congenital Contracture Syndrome 2

MalaCards organs/tissues related to Lethal Congenital Contracture Syndrome 2:

41
Skeletal Muscle, Spinal Cord, Lung, Kidney

Publications for Lethal Congenital Contracture Syndrome 2

Articles related to Lethal Congenital Contracture Syndrome 2:

# Title Authors Year
1
Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3- kinase/Akt pathway. ( 17701904 )
2007
2
Homozygosity mapping of lethal congenital contractural syndrome type 2 (LCCS2) to a 6 cM interval on chromosome 12q13. ( 15378541 )
2004

Variations for Lethal Congenital Contracture Syndrome 2

ClinVar genetic disease variations for Lethal Congenital Contracture Syndrome 2:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ERBB3 ERBB3, IVS10, A-G, -8 single nucleotide variant Pathogenic

Expression for Lethal Congenital Contracture Syndrome 2

Search GEO for disease gene expression data for Lethal Congenital Contracture Syndrome 2.

Pathways for Lethal Congenital Contracture Syndrome 2

Pathways related to Lethal Congenital Contracture Syndrome 2 according to GeneCards Suite gene sharing:

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.51 EGF ERBB3 NTRK1
2
Show member pathways
12.39 EGF ERBB3 NTRK1 PIP5K1C
3 12.3 EGF ERBB3 NTRK1
4
Show member pathways
12.25 EGF ERBB3 PIP5K1C
5
Show member pathways
11.66 ERBB3 NTRK1
6
Show member pathways
11.65 EGF ERBB3
7
Show member pathways
11.56 EGF ERBB3
8
Show member pathways
11.39 EGF NTRK1
9 11.29 ERBB3 NTRK1 PIP5K1C
10 11.06 ERBB3 NTRK1
11 10.97 EGF PIP5K1C
12 10.97 EGF ERBB3 NTRK1
13 10.81 EGF ERBB3
14 10.65 EGF PIP5K1C

GO Terms for Lethal Congenital Contracture Syndrome 2

Cellular components related to Lethal Congenital Contracture Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 receptor complex GO:0043235 8.8 EGF ERBB3 NTRK1

Biological processes related to Lethal Congenital Contracture Syndrome 2 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 9.65 ERBB3 NTRK1 PIP5K1C
2 negative regulation of neuron apoptotic process GO:0043524 9.54 ERBB3 NTRK1
3 membrane organization GO:0061024 9.52 EGF PIP5K1C
4 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007169 9.51 ERBB3 NTRK1
5 negative regulation of signal transduction GO:0009968 9.49 ERBB3 NTRK1
6 positive regulation of kinase activity GO:0033674 9.46 ERBB3 NTRK1
7 activation of MAPKK activity GO:0000186 9.43 EGF NTRK1
8 ERBB2 signaling pathway GO:0038128 9.4 EGF ERBB3
9 positive regulation of protein tyrosine kinase activity GO:0061098 9.37 EGF ERBB3
10 peptidyl-tyrosine phosphorylation GO:0018108 9.33 EGF ERBB3 NTRK1
11 regulation of cell motility GO:2000145 9.32 EGF ERBB3
12 negative regulation of ERBB signaling pathway GO:1901185 9.26 EGF ERBB3
13 phosphatidylinositol phosphorylation GO:0046854 9.13 EGF ERBB3 PIP5K1C
14 negative regulation of secretion GO:0051048 8.62 EGF ERBB3

Molecular functions related to Lethal Congenital Contracture Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 kinase activity GO:0016301 9.54 ERBB3 NTRK1 PIP5K1C
2 Ras guanyl-nucleotide exchange factor activity GO:0005088 9.4 EGF ERBB3
3 MAP kinase kinase kinase activity GO:0004709 9.32 ERBB3 NTRK1
4 mitogen-activated protein kinase kinase binding GO:0031434 9.26 ERBB3 NTRK1
5 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 9.16 EGF ERBB3
6 transmembrane receptor protein tyrosine kinase activity GO:0004714 8.96 ERBB3 NTRK1
7 protein tyrosine kinase activity GO:0004713 8.8 EGF ERBB3 NTRK1

Sources for Lethal Congenital Contracture Syndrome 2

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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