LCCS2
MCID: LTH008
MIFTS: 35

Lethal Congenital Contracture Syndrome 2 (LCCS2)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Respiratory 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 20 72 29 6 44 15 70
Lccs2 57 12 20 58 72
Lethal Congenital Contractural Syndrome 2 57 29 13
Multiple Contracture Syndrome, Israeli-Bedouin Type 12 58
Multiple Contracture Syndrome, Israeli Bedouin Type a 57
Israeli Bedouin Multiple Contracture Syndrome Type a 72
Multiple Contracture Syndrome, Israeli Bedouin Type 20
Contracture Syndrome, Lethal, Congenital, Type 2 39
Lethal Congenital Contracture Syndrome Type 2 58

Characteristics:

Orphanet epidemiological data:

58
lethal congenital contracture syndrome type 2
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: infantile;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

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


HPO:

31
lethal congenital contracture syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060560
OMIM® 57 607598
OMIM Phenotypic Series 57 PS253310
ICD10 via Orphanet 33 Q68.8
UMLS via Orphanet 71 C1843478
Orphanet 58 ORPHA137776
MedGen 41 C1843478
UMLS 70 C1843478

Summaries for Lethal Congenital Contracture Syndrome 2

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 137776 Definition Lethal congenital contracture syndrome 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.

MalaCards based summary : Lethal Congenital Contracture Syndrome 2, also known as lccs2, is related to lethal congenital contracture syndrome 3 and autosomal recessive disease. An important gene associated with Lethal Congenital Contracture Syndrome 2 is ERBB3 (Erb-B2 Receptor Tyrosine Kinase 3). Affiliated tissues include skeletal muscle, spinal cord and kidney, and related phenotypes are dilated cardiomyopathy and ventricular septal defect

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 : 72 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.

More information from OMIM: 607598 PS253310

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

Human phenotypes related to Lethal Congenital Contracture Syndrome 2:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 dilated cardiomyopathy 31 occasional (7.5%) HP:0001644
2 ventricular septal defect 31 occasional (7.5%) HP:0001629
3 skeletal muscle atrophy 31 HP:0003202
4 micrognathia 31 HP:0000347
5 polyhydramnios 31 HP:0001561
6 hydronephrosis 31 HP:0000126
7 decreased fetal movement 31 HP:0001558
8 arthrogryposis multiplex congenita 31 HP:0002804
9 respiratory failure 31 HP:0002878
10 edema 31 HP:0000969
11 akinesia 31 HP:0002304
12 high myopia 31 HP:0011003
13 degenerative vitreoretinopathy 31 HP:0007964

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Respiratory:
respiratory insufficiency
respiratory failure in infancy

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
no fetal hydrops

Prenatal Manifestations Movement:
decreased fetal movement
akinesia

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

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

Genitourinary Kidneys:
hydronephrosis
cystic changes in the kidney

Head And Neck Eyes:
high myopia
degenerative vitreoretinopathy

Skeletal:
arthrogryposis

Genitourinary Bladder:
distended urinary bladder

Clinical features from OMIM®:

607598 (Updated 05-Apr-2021)

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

26 (show all 31)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-109 9.73 GLE1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 9.73 ERBB3
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-151 9.73 GLE1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 9.73 ERBB3
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-168 9.73 PIP5K1C
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-169 9.73 PIP5K1C
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-198 9.73 ERBB3
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.73 ERBB3
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-32 9.73 BRPF3
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-52 9.73 PIP5K1C
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.73 ERBB3
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-76 9.73 BRPF3
13 Increased shRNA abundance (Z-score > 2) GR00366-A-112 9.7 PIP5K1C
14 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.7 PIP5K1C
15 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.7 ERBB3
16 Increased shRNA abundance (Z-score > 2) GR00366-A-130 9.7 PIP5K1C
17 Increased shRNA abundance (Z-score > 2) GR00366-A-139 9.7 PIP5K1C SON
18 Increased shRNA abundance (Z-score > 2) GR00366-A-180 9.7 SON
19 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.7 GLE1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.7 PIP5K1C
21 Increased shRNA abundance (Z-score > 2) GR00366-A-27 9.7 SON
22 Increased shRNA abundance (Z-score > 2) GR00366-A-31 9.7 GLE1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-40 9.7 SON
24 Increased shRNA abundance (Z-score > 2) GR00366-A-48 9.7 GLE1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.7 PIP5K1C
26 Increased shRNA abundance (Z-score > 2) GR00366-A-53 9.7 GLE1 PIP5K1C
27 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.7 ERBB3
28 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.7 SON
29 Increased shRNA abundance (Z-score > 2) GR00366-A-69 9.7 PIP5K1C
30 Increased shRNA abundance (Z-score > 2) GR00366-A-75 9.7 SON
31 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.7 ERBB3 GLE1 PIP5K1C SON

Drugs & Therapeutics for Lethal Congenital Contracture Syndrome 2

Search Clinical Trials , 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
2 Lethal Congenital Contractural Syndrome 2 29

Anatomical Context for Lethal Congenital Contracture Syndrome 2

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

40
Skeletal Muscle, Spinal Cord, Kidney, Lung

Publications for Lethal Congenital Contracture Syndrome 2

Articles related to Lethal Congenital Contracture Syndrome 2:

# Title Authors PMID 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. 57 6 61
17701904 2007
2
Homozygosity mapping of lethal congenital contractural syndrome type 2 (LCCS2) to a 6 cM interval on chromosome 12q13. 61 57
15378541 2004
3
A new autosomal recessive congenital contractural syndrome in an Israeli Bedouin kindred. 57
12548738 2003
4
Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease. 61
18204449 2008
5
Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. 61
17701898 2007

Variations for Lethal Congenital Contracture Syndrome 2

ClinVar genetic disease variations for Lethal Congenital Contracture Syndrome 2:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ERBB3 ERBB3, IVS10AS, A-G, -8 SNV Pathogenic 12572 GRCh37:
GRCh38:
2 ERBB3 NM_001982.4(ERBB3):c.3944del (p.Ser1315fs) Deletion Pathogenic 1030499 GRCh37: 12:56495754-56495754
GRCh38: 12:56101970-56101970
3 ERBB3 NM_001982.4(ERBB3):c.1530G>A (p.Trp510Ter) SNV Pathogenic 1033876 GRCh37: 12:56487597-56487597
GRCh38: 12:56093813-56093813
4 ERBB3 NM_001982.4(ERBB3):c.4027dup (p.Ter1343LeuextTer?) Duplication Pathogenic 1033877 GRCh37: 12:56495836-56495837
GRCh38: 12:56102052-56102053
5 ERBB3 NM_001982.4(ERBB3):c.1253T>C (p.Ile418Thr) SNV Likely pathogenic 978710 GRCh37: 12:56486839-56486839
GRCh38: 12:56093055-56093055
6 ERBB3 NM_001982.4(ERBB3):c.3425C>T (p.Pro1142Leu) SNV Uncertain significance 800957 rs1592232580 GRCh37: 12:56495068-56495068
GRCh38: 12:56101284-56101284
7 ERBB3 NM_001982.3(ERBB3):c.2241G>C (p.Lys747Asn) SNV Uncertain significance 634469 rs760414488 GRCh37: 12:56490597-56490597
GRCh38: 12:56096813-56096813

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

GO Terms for Lethal Congenital Contracture Syndrome 2

Sources for Lethal Congenital Contracture Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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