CRS4
MCID: CRN221
MIFTS: 27

Craniosynostosis 4 (CRS4)

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

Aliases & Classifications for Craniosynostosis 4

MalaCards integrated aliases for Craniosynostosis 4:

Name: Craniosynostosis 4 56 73 71
Crs4 56 73
Familial Lambdoid Synostosis 58
Craniosynostosis, Type 4 39

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
craniosynostosis 4:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Craniosynostosis 4

OMIM : 56 Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Craniosynostosis-4 includes lambdoid, sagittal, metopic, coronal, and multisuture forms. For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100). (600775)

MalaCards based summary : Craniosynostosis 4, also known as crs4, is related to lambdoid synostosis. An important gene associated with Craniosynostosis 4 is ERF (ETS2 Repressor Factor). Affiliated tissues include brain, bone and pituitary, and related phenotypes are flat occiput and plagiocephaly

UniProtKB/Swiss-Prot : 73 Craniosynostosis 4: A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability.

Related Diseases for Craniosynostosis 4

Diseases in the Craniosynostosis family:

Craniosynostosis 1 Craniosynostosis 4
Craniosynostosis 2 Craniosynostosis Syndrome, Autosomal Recessive
Craniosynostosis 3 Craniosynostosis 5
Craniosynostosis 6 Craniosynostosis 7
Craniosynostosis Autosomal Dominant

Diseases related to Craniosynostosis 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 lambdoid synostosis 11.5

Symptoms & Phenotypes for Craniosynostosis 4

Human phenotypes related to Craniosynostosis 4:

58 31 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 flat occiput 58 31 hallmark (90%) Very frequent (99-80%) HP:0005469
2 plagiocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001357
3 stomatocytosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004446
4 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
5 prominent forehead 58 31 frequent (33%) Frequent (79-30%) HP:0011220
6 external ear malformation 58 31 frequent (33%) Frequent (79-30%) HP:0008572
7 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
8 hydrocephalus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000238
9 hypertonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001276
10 protruding ear 58 31 occasional (7.5%) Occasional (29-5%) HP:0000411
11 telecanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000506
12 downturned corners of mouth 58 31 occasional (7.5%) Occasional (29-5%) HP:0002714
13 facial asymmetry 58 31 occasional (7.5%) Occasional (29-5%) HP:0000324
14 round ear 58 31 occasional (7.5%) Occasional (29-5%) HP:0100830
15 blepharophimosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000581
16 macrocephaly 31 occasional (7.5%) HP:0000256
17 short nose 31 occasional (7.5%) HP:0003196
18 optic nerve hypoplasia 31 occasional (7.5%) HP:0000609
19 anterior plagiocephaly 31 occasional (7.5%) HP:0011326
20 ectopic posterior pituitary 31 occasional (7.5%) HP:0011755
21 dimple chin 31 occasional (7.5%) HP:0010751
22 pansynostosis 31 occasional (7.5%) HP:0011325
23 malar flattening 31 HP:0000272
24 hypertelorism 31 HP:0000316
25 frontal bossing 31 HP:0002007
26 midface retrusion 31 HP:0011800
27 retrognathia 31 HP:0000278
28 chin dimple 58 Occasional (29-5%)
29 lambdoidal craniosynostosis 31 HP:0004443
30 posterior plagiocephaly 31 HP:0011327
31 diminished ability to concentrate 31 HP:0031987

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Face:
retrognathia
midface hypoplasia
prominent forehead (major feature)

Head And Neck Head:
macrocephaly (in some patients)

Head And Neck Nose:
short nose (in some patients)
vertical displacement of nose (in some patients)

Skeletal Skull:
sagittal synostosis (in some patients)
lambdoid synostosis (in some patients)
coronal synostosis (in some patients)
pansynostosis (in some patients)

Neurologic Central Nervous System:
learning difficulties
poor concentration
increased intracranial pressure preoperatively (in some patients)
chiari type i malformation (in some patients)
ectopic posterior pituitary (rare)
more
Head And Neck Eyes:
hypertelorism (major feature)
exorbitism (major feature)

Head And Neck Teeth:
dental malocclusion, class i (rare)

Skeletal Hands:
mild shortening of digits (in some patients)

Clinical features from OMIM:

600775

Drugs & Therapeutics for Craniosynostosis 4

Search Clinical Trials , NIH Clinical Center for Craniosynostosis 4

Genetic Tests for Craniosynostosis 4

Anatomical Context for Craniosynostosis 4

MalaCards organs/tissues related to Craniosynostosis 4:

40
Brain, Bone, Pituitary, Testes

Publications for Craniosynostosis 4

Articles related to Craniosynostosis 4:

(show all 15)
# Title Authors PMID Year
1
Heterozygous mutations in ERF cause syndromic craniosynostosis with multiple suture involvement. 56 6
26097063 2015
2
Reduced dosage of ERF causes complex craniosynostosis in humans and mice and links ERK1/2 signaling to regulation of osteogenesis. 56 6
23354439 2013
3
Filling in the gaps in cranial suture biology. 56
23438589 2013
4
Lambdoid synostosis and craniofacial dysmorphism with normal intellect: A novel syndrome? 56
21204239 2011
5
Recurrent lambdoid synostosis within two families. 56
8533829 1995
6
ERF-related craniosynostosis: The phenotypic and developmental profile of a new craniosynostosis syndrome. 61
30758909 2019
7
Biomarkers of cardio-renal syndrome in uremic myocardiopathy animal model. 61
29738042 2018
8
wft4galaxy: a workflow testing tool for galaxy. 61
29036536 2017
9
Clinical therapeutic strategy of recombinant human brain natriuretic peptide and dopamine in cardiorenal syndrome type 4 patients combined with hypotension. 61
29043996 2017
10
Evidence-Based Medicine: Nonsyndromic Craniosynostosis. 61
28654618 2017
11
QTREDS: a Ruby on Rails-based platform for omics laboratories. 61
24564791 2014
12
Simulating systems genetics data with SysGenSIM. 61
21737438 2011
13
Genes regulated by Nkx2-3 in sporadic and inflammatory bowel disease-associated colorectal cancer cell lines. 61
20165982 2010
14
Expression of beta-defensins in the tubotympanum of experimental otitis media. 61
16923707 2006
15
A physiological role for Saccharomyces cerevisiae copper/zinc superoxide dismutase in copper buffering. 61
8530401 1995

Variations for Craniosynostosis 4

ClinVar genetic disease variations for Craniosynostosis 4:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ERF NM_006494.4(ERF):c.23-2A>GSNV Pathogenic 218956 rs864321680 19:42754719-42754719 19:42250567-42250567
2 ERF NM_006494.4(ERF):c.1A>G (p.Met1Val)SNV Pathogenic 218957 rs864321681 19:42759151-42759151 19:42254999-42254999
3 ERF NM_006494.4(ERF):c.547C>T (p.Arg183Ter)SNV Pathogenic 55923 rs587777006 19:42753717-42753717 19:42249565-42249565
4 ERF NM_006494.4(ERF):c.256C>T (p.Arg86Cys)SNV Pathogenic 55925 rs587777008 19:42754484-42754484 19:42250332-42250332
5 ERF NM_006494.4(ERF):c.194G>A (p.Arg65Gln)SNV Pathogenic 55926 rs587777009 19:42754546-42754546 19:42250394-42250394
6 ERF NM_006494.4(ERF):c.1270C>T (p.Gln424Ter)SNV Pathogenic 55927 rs587777010 19:42752994-42752994 19:42248842-42248842
7 ERF NM_006494.4(ERF):c.891_892del (p.Gly299fs)deletion Likely pathogenic 55924 rs587777007 19:42753372-42753373 19:42249220-42249221
8 ERF NM_006494.4(ERF):c.286A>T (p.Lys96Ter)SNV Likely pathogenic 635528 19:42754066-42754066 19:42249914-42249914
9 MYH7 NM_000257.4(MYH7):c.3667G>A (p.Glu1223Lys)SNV Uncertain significance 195928 rs794727410 14:23889113-23889113 14:23419904-23419904
10 46;XY;t(6;11)(q23;q21)or(q25;q21)dnTranslocation Uncertain significance 267823

UniProtKB/Swiss-Prot genetic disease variations for Craniosynostosis 4:

73
# Symbol AA change Variation ID SNP ID
1 ERF p.Arg65Gln VAR_070098 rs587777009
2 ERF p.Arg86Cys VAR_070099 rs587777008

Expression for Craniosynostosis 4

Search GEO for disease gene expression data for Craniosynostosis 4.

Pathways for Craniosynostosis 4

GO Terms for Craniosynostosis 4

Sources for Craniosynostosis 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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30 HMDB
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32 ICD10
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56 OMIM
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61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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