LCCS2
MCID: LTH008
MIFTS: 38

Lethal Congenital Contracture Syndrome 2 (LCCS2)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Respiratory diseases
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Aliases & Classifications for Lethal Congenital Contracture Syndrome 2

MalaCards integrated aliases for Lethal Congenital Contracture Syndrome 2:

Name: Lethal Congenital Contracture Syndrome 2 57 11 19 73 28 5 43 14 71
Lccs2 57 11 19 58 73
Multiple Contracture Syndrome, Israeli-Bedouin Type 11 58
Lethal Congenital Contractural Syndrome 2 57 12
Multiple Contracture Syndrome, Israeli Bedouin Type a 57
Israeli Bedouin Multiple Contracture Syndrome Type a 73
Multiple Contracture Syndrome, Israeli Bedouin Type 19
Contracture Syndrome, Lethal, Congenital, Type 2 38
Lethal Congenital Contracture Syndrome Type 2 58

Characteristics:


Inheritance:

Lethal Congenital Contracture Syndrome 2: Autosomal recessive 57
Lethal Congenital Contracture Syndrome Type 2: Autosomal recessive 58

Prevelance:

Lethal Congenital Contracture Syndrome Type 2: <1/1000000 (Worldwide) 58

Age Of Onset:

Lethal Congenital Contracture Syndrome Type 2: Antenatal,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
most affected infants die shortly after birth from respiratory failure


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 11 DOID:0060560
OMIM® 57 607598
OMIM Phenotypic Series 57 PS253310
ICD10 via Orphanet 32 Q68.8
UMLS via Orphanet 72 C1843478
Orphanet 58 ORPHA137776
MedGen 40 C1843478
UMLS 71 C1843478

Summaries for Lethal Congenital Contracture Syndrome 2

UniProtKB/Swiss-Prot: 73 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 3 and distal arthrogryposis. An important gene associated with Lethal Congenital Contracture Syndrome 2 is ERBB3 (Erb-B2 Receptor Tyrosine Kinase 3), and among its related pathways/superpathways is Striated muscle contraction pathway. Affiliated tissues include skeletal muscle, spinal cord and bone, and related phenotypes are dilated cardiomyopathy and ventricular septal defect

GARD: 19 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.

Orphanet: 58 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.

OMIM®: 57 Lethal congenital contracture syndrome-2 (LCCS2) is an autosomal recessive disorder characterized by severe multiple congenital contractures with muscle wasting and atrophy. Micrognathia and other craniofacial anomalies, including cleft palate, as well as cardiac defects and enlarged urinary bladder at birth have also been reported. Hydrops fetalis and multiple pterygia are absent. Most patients have died in the neonatal period, although 2 survived to early adolescence (Landau et al., 2003). For a general phenotypic description and a discussion of genetic heterogeneity of LCCS, see LCCS1 (253310). (607598) (Updated 08-Dec-2022)

Disease Ontology: 11 A lethal congenital contracture syndrome that can be that has material basis in homozygous mutation in the ERBB3 gene on chromosome 12q13.

Related Diseases for Lethal Congenital Contracture Syndrome 2

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:

(show all 19)
# Related Disease Score Top Affiliating Genes
1 lethal congenital contracture syndrome 3 31.6 PIP5K1C MYBPC1
2 distal arthrogryposis 28.1 ZBTB42 PIP5K1C MYBPC2 MYBPC1 GLE1 GLDN
3 myasthenic syndrome, congenital, 4b, fast-channel 10.0 MYBPC1 GLE1
4 neurogenic bladder 10.0 PIP5K1C ERBB3
5 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 10.0 MYBPC1 GLE1
6 anterior horn cell disease 10.0 SON GLE1
7 oto-palatal-digital syndrome 10.0
8 arthrogryposis, distal, type 10 9.9 ZBTB42 MYBPC1 GLE1
9 arthrogryposis, distal, type 7 9.9 ZBTB42 MYBPC1 GLE1
10 fetal akinesia deformation sequence 1 9.9 GLE1 GLDN
11 multiple pterygium syndrome, escobar variant 9.8 PIP5K1C MYBPC1 GLDN
12 demyelinating polyneuropathy 9.8 GLDN ADGRG6
13 cardiomyopathy, familial hypertrophic, 4 9.8 MYBPC2 MYBPC1
14 polyhydramnios 9.7 ZBTB42 GLDN
15 arthrogryposis, distal, type 2a 9.7 MYBPC2 MYBPC1
16 lethal congenital contracture syndrome 4 9.5 MYBPC2 MYBPC1 ADGRG6
17 lethal congenital contracture syndrome 1 9.5 ZBTB42 SON PIP5K1C MYBPC1 GLE1
18 arthrogryposis, distal, type 5 8.8 ZBTB42 PIP5K1C MYBPC2 MYBPC1 GLE1 GLDN
19 lethal congenital contracture syndrome 8.5 ZBTB42 SON PIP5K1C NEK9 MYBPC1 GLE1

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:

30 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dilated cardiomyopathy 30 Occasional (7.5%) HP:0001644
2 ventricular septal defect 30 Occasional (7.5%) HP:0001629
3 skeletal muscle atrophy 30 HP:0003202
4 micrognathia 30 HP:0000347
5 polyhydramnios 30 HP:0001561
6 hydronephrosis 30 HP:0000126
7 decreased fetal movement 30 HP:0001558
8 arthrogryposis multiplex congenita 30 HP:0002804
9 respiratory failure 30 HP:0002878
10 edema 30 HP:0000969
11 akinesia 30 HP:0002304
12 high myopia 30 HP:0011003
13 degenerative vitreoretinopathy 30 HP:0007964

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
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 08-Dec-2022)

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

25 (show all 26)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-112 9.94 PIP5K1C
2 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.94 PIP5K1C
3 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.94 ERBB3
4 Increased shRNA abundance (Z-score > 2) GR00366-A-130 9.94 PIP5K1C
5 Increased shRNA abundance (Z-score > 2) GR00366-A-139 9.94 PIP5K1C SON
6 Increased shRNA abundance (Z-score > 2) GR00366-A-180 9.94 SON
7 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.94 GLE1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-188 9.94 PIP5K1C
9 Increased shRNA abundance (Z-score > 2) GR00366-A-27 9.94 SON
10 Increased shRNA abundance (Z-score > 2) GR00366-A-31 9.94 GLE1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-40 9.94 SON
12 Increased shRNA abundance (Z-score > 2) GR00366-A-48 9.94 GLE1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-50 9.94 PIP5K1C
14 Increased shRNA abundance (Z-score > 2) GR00366-A-53 9.94 GLE1 PIP5K1C
15 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.94 ERBB3
16 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.94 SON
17 Increased shRNA abundance (Z-score > 2) GR00366-A-69 9.94 PIP5K1C
18 Increased shRNA abundance (Z-score > 2) GR00366-A-75 9.94 SON
19 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.94 ERBB3 GLE1 PIP5K1C SON
20 Decreased viability GR00106-A-0 9.65 ERBB3
21 Decreased viability GR00173-A 9.65 NEK9
22 Decreased viability GR00221-A-1 9.65 NEK9
23 Decreased viability GR00221-A-2 9.65 ERBB3 PIP5K1C
24 Decreased viability GR00221-A-4 9.65 ERBB3 NEK9 PIP5K1C
25 Decreased viability GR00301-A 9.65 ERBB3
26 Decreased viability GR00402-S-2 9.65 NEK9

MGI Mouse Phenotypes related to Lethal Congenital Contracture Syndrome 2:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.23 ADGRG6 ERBB3 GLDN GLE1 MYBPC1 MYBPC2

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 28 ERBB3

Anatomical Context for Lethal Congenital Contracture Syndrome 2

Organs/tissues related to Lethal Congenital Contracture Syndrome 2:

MalaCards : Skeletal Muscle, Spinal Cord, Bone, Lung, Kidney

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. 62 57 5
17701904 2007
2
Homozygosity mapping of lethal congenital contractural syndrome type 2 (LCCS2) to a 6 cM interval on chromosome 12q13. 62 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. 62
18204449 2008
5
Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. 62
17701898 2007

Variations for Lethal Congenital Contracture Syndrome 2

ClinVar genetic disease variations for Lethal Congenital Contracture Syndrome 2:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ERBB3 NM_001982.4(ERBB3):c.1184-9A>G SNV Pathogenic
12572 GRCh37: 12:56486761-56486761
GRCh38: 12:56092977-56092977
2 ERBB3 NM_001982.4(ERBB3):c.1253T>C (p.Ile418Thr) SNV Likely Pathogenic
978710 rs141230043 GRCh37: 12:56486839-56486839
GRCh38: 12:56093055-56093055
3 ERBB3 NM_001982.4(ERBB3):c.3425C>T (p.Pro1142Leu) SNV Likely Pathogenic
800957 rs1592232580 GRCh37: 12:56495068-56495068
GRCh38: 12:56101284-56101284
4 ERBB3 NM_001982.4(ERBB3):c.2241G>C (p.Lys747Asn) SNV Uncertain Significance
634469 rs760414488 GRCh37: 12:56490597-56490597
GRCh38: 12:56096813-56096813
5 ERBB3 NM_001982.4(ERBB3):c.3129+9A>C SNV Benign
1226099 GRCh37: 12:56493822-56493822
GRCh38: 12:56100038-56100038
6 ERBB3 NM_001982.4(ERBB3):c.3348G>A (p.Arg1116=) SNV Benign
1248586 GRCh37: 12:56494991-56494991
GRCh38: 12:56101207-56101207
7 ERBB3 NM_001982.4(ERBB3):c.234+8A>T SNV Benign
1255390 GRCh37: 12:56477694-56477694
GRCh38: 12:56083910-56083910
8 ERBB3 NM_001982.4(ERBB3):c.2616+16G>C SNV Benign
1255391 GRCh37: 12:56491740-56491740
GRCh38: 12:56097956-56097956

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:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.49 MYBPC2 MYBPC1

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 myosin filament GO:0032982 8.92 MYBPC2 MYBPC1

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

# Name GO ID Score Top Affiliating Genes
1 Schwann cell differentiation GO:0014037 8.92 ERBB3 ADGRG6

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

# Name GO ID Score Top Affiliating Genes
1 structural constituent of muscle GO:0008307 8.92 MYBPC2 MYBPC1

Sources for Lethal Congenital Contracture Syndrome 2

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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