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LCCS2
MCID: LTH008
MIFTS: 43

Lethal Congenital Contracture Syndrome 2 (LCCS2)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases
Genes Variations Tissues Related diseases Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Lethal Congenital Contracture Syndrome 2

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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:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Respiratory diseases Neuronal diseases Bone diseases Nephrological diseases
See all MalaCards categories (disease lists)
ICD10: 34
Orphanet: 59  
Developmental anomalies during embryogenesis


Sources

Summaries for Lethal Congenital Contracture Syndrome 2

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NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 137776Disease definitionLethal congenitalcontracturesyndrome type 2 is a rare arthrogryposis syndrome characterized by multiple congenital contactures (typically extended elbows and flexed knees), micrognathia, anterior horn cell degeneration, skeletal muscle atrophy (mainly in the lower limbs), presence of a markedly distended urinary bladder and absence of hydrops, pterygia and bone fractures. Other craniofacial (e.g. cleft palate, facial palsy) and ocular (e.g. anisocoria, retinal detachment) anomalies may be additionally observed. The disease is usually neonatally lethal however, survival into adolescence has been reported.Visit the Orphanet disease page for more resources.

MalaCards based summary : Lethal Congenital Contracture Syndrome 2, also known as lccs2, is related to lethal congenital contracture syndrome 3 and mesenteric lymphadenitis. 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 Actin Nucleation by ARP-WASP Complex and PI3K-Akt signaling pathway. 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 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.

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.

Description from OMIM: 607598
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Related Diseases for Lethal Congenital Contracture Syndrome 2

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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 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 lethal congenital contracture syndrome 3 11.1
2 mesenteric lymphadenitis 9.9 EGF ERBB3
3 neurogenic bladder 9.9 ERBB3 PIP5K1C
4 lethal congenital contracture syndrome 9.7 ERBB3 GLE1 PIP5K1C
5 lethal congenital contracture syndrome 1 9.7 ERBB3 GLE1 PIP5K1C
6 differentiated thyroid carcinoma 9.7 EGF NTRK1

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



Diseases related to Lethal Congenital Contracture Syndrome 2
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Symptoms & Phenotypes for Lethal Congenital Contracture Syndrome 2

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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 dilated cardiomyopathy 32 occasional (7.5%) HP:0001644
5 arthrogryposis multiplex congenita 32 HP:0002804
6 respiratory failure 32 HP:0002878
7 polyhydramnios 32 HP:0001561
8 ventricular septal defect 32 occasional (7.5%) HP:0001629
9 decreased fetal movement 32 HP:0001558
10 hydronephrosis 32 HP:0000126
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 10 GLE1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 10 PIP5K1C
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10 ERBB3
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 10 NTRK1 PIP5K1C
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-20 10 NTRK1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10 ERBB3
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 10 GLE1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 10 ERBB3 GLE1 NTRK1 PIP5K1C
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-60 10 ERBB3 NTRK1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.66 PIP5K1C
11 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.66 ERBB3
12 Increased shRNA abundance (Z-score > 2) GR00366-A-130 9.66 PIP5K1C
13 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.66 GLE1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.66 ERBB3
15 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.66 NTRK1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.66 PIP5K1C
17 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.66 PIP5K1C
18 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.66 GLE1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.66 PIP5K1C
20 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.66 ERBB3
21 Increased shRNA abundance (Z-score > 2) GR00366-A-31 9.66 GLE1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.66 NTRK1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.66 PIP5K1C
24 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.66 NTRK1 PIP5K1C
25 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.66 NTRK1
26 Increased shRNA abundance (Z-score > 2) GR00366-A-69 9.66 PIP5K1C
27 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.66 ERBB3 GLE1 NTRK1 PIP5K1C
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
Sources

Drugs & Therapeutics for Lethal Congenital Contracture Syndrome 2

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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
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

Search NIH Clinical Center for Lethal Congenital Contracture Syndrome 2

Cochrane evidence based reviews: lethal congenital contracture syndrome 2

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Genetic Tests for Lethal Congenital Contracture Syndrome 2

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Genetic tests related to Lethal Congenital Contracture Syndrome 2:

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

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

41
Skeletal Muscle, Bone, Spinal Cord, Lung, Kidney, Thyroid
Sources

Publications for Lethal Congenital Contracture Syndrome 2

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Variations for Lethal Congenital Contracture Syndrome 2

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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
Sources

Expression for Lethal Congenital Contracture Syndrome 2

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

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

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Actin Nucleation by ARP-WASP Complex 64
Show member pathways
 12.58 ERBB3 NTRK1 PIP5K1C
2
PI3K-Akt signaling pathway 37
Show member pathways
 12.57 EGF ERBB3 NTRK1
3
PI3K/AKT activation 66
Show member pathways
 12.55 EGF ERBB3 NTRK1 PIP5K1C
4
MAPK signaling pathway 37 1
12.37 EGF ERBB3 NTRK1
5
Downstream signaling events of B Cell Receptor (BCR) 66
Show member pathways
 12.33 EGF ERBB3 PIP5K1C
6
MAPK Signaling: Mitogen Stimulation Pathway 65
Show member pathways
 11.76 ERBB3 NTRK1 PIP5K1C
7
Signaling by PTK6 66
Show member pathways
 11.69 EGF ERBB3
8
AKT Signaling Pathway 67
11.59 ERBB3 NTRK1 PIP5K1C
9
Signaling by ERBB4 66
Show member pathways
 11.58 EGF ERBB3
10
Tyrosine Kinases / Adaptors 4
11.5 EGF ERBB3 NTRK1
11
Endocytic Trafficking of EGFR 64
Show member pathways
 11.43 EGF NTRK1
12
G-protein signaling_RhoA regulation pathway 22
11.32 EGF ERBB3 NTRK1
13
G-protein signaling RAC1 in cellular process 22
Show member pathways
 11.22 EGF ERBB3 NTRK1 PIP5K1C
14
Alzheimers Disease Pathway 64
11.15 ERBB3 NTRK1
15
Stabilization and expansion of the E-cadherin adherens junction 1
11.08 EGF PIP5K1C
16
a6b1 and a6b4 Integrin signaling 1
10.92 EGF ERBB3
17
EGF receptor (ErbB1) signaling pathway 1
10.77 EGF PIP5K1C
18
G-protein signaling_Rap2B regulation pathway 22
10.16 EGF ERBB3 NTRK1 PIP5K1C
Sources

GO Terms for Lethal Congenital Contracture Syndrome 2

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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 13)
# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 9.63 ERBB3 NTRK1 PIP5K1C
2 negative regulation of neuron apoptotic process GO:0043524 9.52 ERBB3 NTRK1
3 positive regulation of MAPK cascade GO:0043410 9.51 ERBB3 NTRK1
4 membrane organization GO:0061024 9.49 EGF PIP5K1C
5 negative regulation of signal transduction GO:0009968 9.48 ERBB3 NTRK1
6 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007169 9.43 ERBB3 NTRK1
7 activation of MAPKK activity GO:0000186 9.4 EGF NTRK1
8 positive regulation of protein tyrosine kinase activity GO:0061098 9.37 EGF ERBB3
9 peptidyl-tyrosine phosphorylation GO:0018108 9.33 EGF ERBB3 NTRK1
10 ERBB2 signaling pathway GO:0038128 9.32 EGF ERBB3
11 regulation of cell motility GO:2000145 9.26 EGF ERBB3
12 phosphatidylinositol phosphorylation GO:0046854 9.13 EGF ERBB3 PIP5K1C
13 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 9.43 ERBB3 NTRK1 PIP5K1C
2 Ras guanyl-nucleotide exchange factor activity GO:0005088 9.32 EGF ERBB3
3 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 9.16 EGF ERBB3
4 transmembrane receptor protein tyrosine kinase activity GO:0004714 8.96 ERBB3 NTRK1
5 protein tyrosine kinase activity GO:0004713 8.8 EGF ERBB3 NTRK1
Sources

Sources for Lethal Congenital Contracture Syndrome 2

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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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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