MCID: GRG001
MIFTS: 53

Greig Cephalopolysyndactyly Syndrome

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

Aliases & Classifications for Greig Cephalopolysyndactyly Syndrome

MalaCards integrated aliases for Greig Cephalopolysyndactyly Syndrome:

Name: Greig Cephalopolysyndactyly Syndrome 53 12 23 49 24 55 28 13 51 41 14
Gcps 53 49 24 55 71
Polysyndactyly with Peculiar Skull Shape 53 49
Cephalopolysyndactyly Syndrome 23 24
Polysyndactyly with Peculiars Skull Shape 12
Greig Cephalo-Poly-Syndactyly Syndrome 71
Aarskog Syndrome 69
Greig Syndrome 49

Characteristics:

Orphanet epidemiological data:

55
greig cephalopolysyndactyly syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/1000000 (Europe); Age of onset: Neonatal;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
variable expressivity


HPO:

31
greig cephalopolysyndactyly syndrome:
Onset and clinical course variable expressivity
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance One case of apparent non-penetrance has been reported [debeer et al 2003]. it is difficult to estimate a rate of non-penetrance from a single instance, but it is probably a small fraction...

Classifications:



Summaries for Greig Cephalopolysyndactyly Syndrome

NIH Rare Diseases : 49 Greig cephalopolysyndactyly syndrome (GCPS) is a congenital disorder that affects development of the limbs, head, and face. Findings might include an extra finger or toe (polydactyly), fusion of the skin between the fingers or toes (syndactyly), widely spaced eyes (ocular hypertelorism), and an abnormally large head size (macrocephaly).The features of this syndrome are highly variable, ranging from polydactyly and syndactyly of the upper and/or lower limbs to seizure, hydrocephalus , and intellectual disability. Progression of GCPS is dependent on severity. Greig cephalopolysyndactyly syndrome is caused by mutations in the GLI3 gene. This condition is inherited in an autosomal dominant pattern. Treatment is symptomatic. Last updated: 12/10/2015

MalaCards based summary : Greig Cephalopolysyndactyly Syndrome, also known as gcps, is related to acrocallosal syndrome and polydactyly, and has symptoms including seizures, macrocephaly and hypertelorism. An important gene associated with Greig Cephalopolysyndactyly Syndrome is GLI3 (GLI Family Zinc Finger 3), and among its related pathways/superpathways are Pathways in cancer and Signaling by Hedgehog. The drug Menthol has been mentioned in the context of this disorder. Affiliated tissues include skin, eye and bone, and related phenotype is Increased Nanog expression.

Disease Ontology : 12 An acrocephalosyndactylia that has material basis in mutation in the GLI3 gene which results_in abnormal development located in limb, located in head, located in face.

Genetics Home Reference : 24 Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux). The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures, delayed development, and intellectual disability.

OMIM : 53 Greig cephalopolysyndactyly syndrome is characterized by frontal bossing, scaphocephaly, and hypertelorism associated with pre- and postaxial polydactyly and variable syndactyly. The phenotype shows variable expressivity and can also include craniosynostosis. Affected individuals usually have normal psychomotor development (summary by Gorlin et al., 2001). (175700)

UniProtKB/Swiss-Prot : 71 Greig cephalo-poly-syndactyly syndrome: Autosomal dominant disorder affecting limb and craniofacial development. It is characterized by pre- and postaxial polydactyly, syndactyly of fingers and toes, macrocephaly and hypertelorism.

Wikipedia : 72 Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and... more...

GeneReviews: NBK1446

Related Diseases for Greig Cephalopolysyndactyly Syndrome

Diseases related to Greig Cephalopolysyndactyly Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 acrocallosal syndrome 30.0 GLI3 KIF7
2 polydactyly 30.0 GLI2 GLI3
3 pallister-hall syndrome 29.7 GLI2 GLI3 KIF7
4 synostosis 10.1
5 esotropia 10.1
6 chromosome 7p deletion 10.1
7 esophageal atresia 10.1 GLI2 GLI3
8 infratentorial cancer 10.0 GLI2 GLI3
9 blood group, i system 10.0
10 basal cell nevus syndrome 9.9 GLI2 GLI3
11 prostate cancer 9.8
12 crohn's disease 9.8
13 holoprosencephaly 9.7 GLI2 GLI3

Graphical network of the top 20 diseases related to Greig Cephalopolysyndactyly Syndrome:



Diseases related to Greig Cephalopolysyndactyly Syndrome

Symptoms & Phenotypes for Greig Cephalopolysyndactyly Syndrome

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Head:
macrocephaly
trigonocephaly
scaphocephaly

Neurologic Central Nervous System:
agenesis of corpus callosum
normal intelligence
mental retardation, mild (rare)
hydrocephaly

Genitourinary External Genitalia Male:
inguinal hernia

Skeletal Skull:
craniosynostosis
broad late closing cranial sutures
metopic synostosis (rare)

Skeletal Feet:
camptodactyly
preaxial polydactyly
broad halluces
syndactyly (usually toes 1 to 3)
postaxial polydactyly (rare)

Head And Neck Nose:
broad nasal root

Head And Neck Eyes:
hypertelorism
downslanting palpebral fissures

Head And Neck Face:
frontal bossing
high forehead

Abdomen External Features:
umbilical hernia

Skeletal Hands:
camptodactyly
postaxial polydactyly
broad thumbs
syndactyly (usually fingers 3 and 4)
preaxial polydactyly (variable)

Skeletal:
advanced bone age

Laboratory Abnormalities:
translocation or deletions involving 7p13 (severe case reports)


Clinical features from OMIM:

175700

Human phenotypes related to Greig Cephalopolysyndactyly Syndrome:

55 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 occasional (7.5%) Occasional (29-5%) HP:0001250
2 macrocephaly 55 31 very rare (1%) Very frequent (99-80%) HP:0000256
3 hypertelorism 55 31 frequent (33%) Frequent (79-30%) HP:0000316
4 agenesis of corpus callosum 55 31 occasional (7.5%) Occasional (29-5%) HP:0001274
5 frontal bossing 55 31 very rare (1%) Frequent (79-30%) HP:0002007
6 finger syndactyly 55 31 frequent (33%) Frequent (79-30%) HP:0006101
7 hydrocephalus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000238
8 wide nasal bridge 55 31 very rare (1%) Frequent (79-30%) HP:0000431
9 umbilical hernia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001537
10 broad hallux phalanx 55 31 frequent (33%) Occasional (29-5%) HP:0010059
11 broad thumb 55 31 frequent (33%) Occasional (29-5%) HP:0011304
12 intellectual disability, mild 55 31 occasional (7.5%) Occasional (29-5%) HP:0001256
13 telecanthus 55 31 frequent (33%) Frequent (79-30%) HP:0000506
14 high forehead 55 31 very rare (1%) Frequent (79-30%) HP:0000348
15 craniosynostosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001363
16 preaxial hand polydactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001177
17 toe syndactyly 55 31 frequent (33%) Frequent (79-30%) HP:0001770
18 postaxial hand polydactyly 55 31 very rare (1%) Very frequent (99-80%) HP:0001162
19 postaxial foot polydactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001830
20 congenital diaphragmatic hernia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000776
21 accelerated skeletal maturation 55 31 occasional (7.5%) Frequent (79-30%) HP:0005616
22 preaxial foot polydactyly 55 31 frequent (33%) Very frequent (99-80%) HP:0001841
23 inguinal hernia 31 occasional (7.5%) HP:0000023
24 cryptorchidism 31 occasional (7.5%) HP:0000028
25 hypospadias 31 occasional (7.5%) HP:0000047
26 downslanted palpebral fissures 31 occasional (7.5%) HP:0000494
27 abnormality of muscle fibers 31 occasional (7.5%) HP:0004303
28 trigonocephaly 31 HP:0000243
29 abnormality of calvarial morphology 31 occasional (7.5%) HP:0002648
30 delayed cranial suture closure 31 occasional (7.5%) HP:0000270
31 hirsutism 31 occasional (7.5%) HP:0001007
32 abnormal heart morphology 31 occasional (7.5%) HP:0001627
33 camptodactyly of toe 31 occasional (7.5%) HP:0001836
34 hyperglycemia 31 occasional (7.5%) HP:0003074
35 broad hallux 31 very rare (1%) HP:0010055
36 joint contracture of the hand 31 occasional (7.5%) HP:0009473
37 metopic synostosis 31 occasional (7.5%) HP:0011330
38 3-4 finger syndactyly 31 frequent (33%) HP:0006097
39 scaphocephaly 31 HP:0030799
40 1-3 toe syndactyly 31 very rare (1%) HP:0001459

GenomeRNAi Phenotypes related to Greig Cephalopolysyndactyly Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased Nanog expression GR00371-A-5 8.8 GLI2 GLI3 PGAM2

Drugs & Therapeutics for Greig Cephalopolysyndactyly Syndrome

Drugs for Greig Cephalopolysyndactyly Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Menthol Approved 2216-51-5 16666

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phenotype and Etiology of Pallister-Hall Syndrome Completed NCT00001404

Search NIH Clinical Center for Greig Cephalopolysyndactyly Syndrome

Cochrane evidence based reviews: greig cephalopolysyndactyly syndrome

Genetic Tests for Greig Cephalopolysyndactyly Syndrome

Genetic tests related to Greig Cephalopolysyndactyly Syndrome:

# Genetic test Affiliating Genes
1 Greig Cephalopolysyndactyly Syndrome 28 GLI3

Anatomical Context for Greig Cephalopolysyndactyly Syndrome

MalaCards organs/tissues related to Greig Cephalopolysyndactyly Syndrome:

38
Skin, Eye, Bone, Heart, Pancreas

The Foundational Model of Anatomy Ontology organs/tissues related to Greig Cephalopolysyndactyly Syndrome:

18
Limb, Head, Face

Publications for Greig Cephalopolysyndactyly Syndrome

Articles related to Greig Cephalopolysyndactyly Syndrome:

(show all 31)
# Title Authors Year
1
Novel GLI3 variant causing overlapped Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS) phenotype with agenesis of gallbladder and pancreas. ( 29368652 )
2018
2
Novel GLI3 mutation in a Greek-Cypriot patient with Greig cephalopolysyndactyly syndrome. ( 25714367 )
2015
3
A novel GLI3c.750delC truncation mutation in a multiplex Greig cephalopolysyndactyly syndrome family with an unusual phenotypic combination in a patient. ( 25606469 )
2014
4
Prenatal diagnosis of Greig cephalopolysyndactyly syndrome: a case report. ( 25297527 )
2014
5
Crossed polydactyly and Greig cephalopolysyndactyly syndrome. ( 24222286 )
2013
6
Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome: five cases with intragenic mutations or complete deletions of GLI3. ( 21326280 )
2011
7
MODY type 2 in Greig cephalopolysyndactyly syndrome (GCPS) as part of a contiguous gene deletion syndrome. ( 22043488 )
2011
8
Greig cephalopolysyndactyly syndrome: diagnosis based on prenatal sonographic features coupled with comparative genomic hybridization. ( 19933491 )
2009
9
The clinical atlas of Greig cephalopolysyndactyly syndrome. ( 18241058 )
2008
10
The Greig cephalopolysyndactyly syndrome. ( 18435847 )
2008
11
Greig cephalopolysyndactyly syndrome in a family. ( 16927636 )
2006
12
Japanese family with Greig cephalopolysyndactyly syndrome, including bilateral seven toes, and esotropia, over three generations. ( 16912002 )
2006
13
Genomic analysis of five chromosome 7p deletion patients with Greig cephalopolysyndactyly syndrome (GCPS). ( 16829355 )
2006
14
Gene symbol: GLI3. Disease: Greig cephalopolysyndactyly syndrome. ( 12575660 )
2003
15
Variable phenotype in Greig cephalopolysyndactyly syndrome: clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations. ( 12794692 )
2003
16
A Turkish family with Greig cephalopolysyndactyly syndrome. ( 10770668 )
1999
17
Greig cephalopolysyndactyly syndrome: altered phenotype of a microdeletion syndrome due to the presence of a cytogenetic abnormality. ( 9520255 )
1997
18
Greig cephalopolysyndactyly syndrome with dysgenesis of the corpus callosum in a Bedouin family. ( 8985483 )
1996
19
Isolation of a yeast artificial chromosome contig spanning the Greig cephalopolysyndactyly syndrome (GCPS) gene region. ( 8001967 )
1994
20
Greig cephalopolysyndactyly syndrome in a large family: a comparison of the clinical signs with those described in the literature. ( 8205322 )
1994
21
A mouse model of greig cephalopolysyndactyly syndrome: the extra-toesJ mutation contains an intragenic deletion of the Gli3 gene. ( 8387379 )
1993
22
Greig Cephalopolysyndactyly Syndrome ( 20301619 )
1993
23
Deletion of GLI3 supports the homology of the human Greig cephalopolysyndactyly syndrome (GCPS) and the mouse mutant extra toes (Xt). ( 1322743 )
1992
24
A 2.5-Mb physical map within 3p21.1 spans the breakpoint associated with Greig cephalopolysyndactyly syndrome. ( 1662666 )
1991
25
Greig cephalopolysyndactyly syndrome: a possible mouse homologue (Xt-extra toes). ( 3239570 )
1988
26
The occurrence of a fibro-osseous lesion and multiple dental anomalies in a patient with the Greig cephalopolysyndactyly syndrome. ( 2847100 )
1988
27
The Greig cephalopolysyndactyly syndrome. ( 3025136 )
1986
28
Greig cephalopolysyndactyly syndrome. Report of a sporadic case. ( 3007398 )
1985
29
The Greig cephalopolysyndactyly syndrome: report of a family and review of the literature. ( 3901752 )
1985
30
The Greig cephalopolysyndactyly syndrome in a Canadian family. ( 6295159 )
1982
31
Greig cephalopolysyndactyly syndrome. ( 223435 )
1979

Variations for Greig Cephalopolysyndactyly Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Greig Cephalopolysyndactyly Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 GLI3 p.Cys515Gly VAR_010053
2 GLI3 p.Cys520Tyr VAR_010054
3 GLI3 p.Pro707Ser VAR_010055 rs121917716
4 GLI3 p.Ile808Met VAR_010056 rs62622373
5 GLI3 p.Arg625Trp VAR_021481 rs121917712
6 GLI3 p.Ala934Pro VAR_021482 rs28933372

ClinVar genetic disease variations for Greig Cephalopolysyndactyly Syndrome:

6 (show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 GLI3 GLI3, DEL deletion Pathogenic
2 GLI3 NM_000168.5(GLI3): c.1627G> T (p.Glu543Ter) single nucleotide variant Pathogenic rs121917711 GRCh37 Chromosome 7, 42018218: 42018218
3 GLI3 NM_000168.5(GLI3): c.1873C> T (p.Arg625Trp) single nucleotide variant Pathogenic rs121917712 GRCh37 Chromosome 7, 42012166: 42012166
4 GLI3 NM_000168.5(GLI3): c.868C> T (p.Arg290Ter) single nucleotide variant Pathogenic rs121917713 GRCh37 Chromosome 7, 42079797: 42079797
5 GLI3 NM_000168.5(GLI3): c.2374C> T (p.Arg792Ter) single nucleotide variant Pathogenic rs121917714 GRCh37 Chromosome 7, 42007251: 42007251
6 GLI3 NM_000168.5(GLI3): c.1486C> T (p.Gln496Ter) single nucleotide variant Pathogenic rs121917715 GRCh37 Chromosome 7, 42063078: 42063078
7 GLI3 GLI3, 4-BP DEL, 4542CCAC deletion Pathogenic
8 GLI3 GLI3, 1-BP DEL, 1018A deletion Pathogenic
9 GLI3 NM_000168.5(GLI3): c.2685C> G (p.Tyr895Ter) single nucleotide variant Pathogenic rs772948115 GRCh38 Chromosome 7, 41966388: 41966388
10 GLI3 NM_000168.5(GLI3): c.1878delA (p.Lys626Asnfs) deletion Pathogenic GRCh38 Chromosome 7, 41972562: 41972562
11 GLI3 NM_000168.5(GLI3): c.4395delC (p.Ser1466Alafs) deletion Pathogenic GRCh37 Chromosome 7, 42004276: 42004276

Copy number variations for Greig Cephalopolysyndactyly Syndrome from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 225048 7 41967072 42243321 Deletion GLI3 Greig cephalo-polysyndactyly syndrome
2 225147 7 43300000 46600000 Copy number GLI3 Greig cephalo-polysyndactyly syndrome

Expression for Greig Cephalopolysyndactyly Syndrome

Search GEO for disease gene expression data for Greig Cephalopolysyndactyly Syndrome.

Pathways for Greig Cephalopolysyndactyly Syndrome

GO Terms for Greig Cephalopolysyndactyly Syndrome

Cellular components related to Greig Cephalopolysyndactyly Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cilium GO:0005929 9.33 GLI2 GLI3 KIF7
2 axoneme GO:0005930 9.26 GLI2 GLI3
3 ciliary base GO:0097546 8.96 GLI2 GLI3
4 ciliary tip GO:0097542 8.8 GLI2 GLI3 KIF7

Biological processes related to Greig Cephalopolysyndactyly Syndrome according to GeneCards Suite gene sharing:

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.8 ACY1 GCK PGAM2
2 kidney development GO:0001822 9.64 GLI2 GLI3
3 anterior/posterior pattern specification GO:0009952 9.63 GLI2 GLI3
4 lung development GO:0030324 9.63 GLI2 GLI3
5 smoothened signaling pathway GO:0007224 9.62 GLI2 GLI3
6 embryonic digit morphogenesis GO:0042733 9.61 GLI2 GLI3
7 odontogenesis of dentin-containing tooth GO:0042475 9.61 GLI2 GLI3
8 pattern specification process GO:0007389 9.6 GLI2 GLI3
9 neural tube development GO:0021915 9.59 GLI2 GLI3
10 dorsal/ventral pattern formation GO:0009953 9.58 GLI2 GLI3
11 glycolytic process GO:0006096 9.58 GCK PGAM2
12 mammary gland development GO:0030879 9.57 GLI2 GLI3
13 developmental growth GO:0048589 9.56 GLI2 GLI3
14 branching morphogenesis of an epithelial tube GO:0048754 9.55 GLI2 GLI3
15 canonical glycolysis GO:0061621 9.54 GCK PGAM2
16 proximal/distal pattern formation GO:0009954 9.52 GLI2 GLI3
17 negative regulation of smoothened signaling pathway GO:0045879 9.51 GLI3 KIF7
18 spinal cord motor neuron differentiation GO:0021522 9.49 GLI2 GLI3
19 embryonic digestive tract development GO:0048566 9.48 GLI2 GLI3
20 anatomical structure formation involved in morphogenesis GO:0048646 9.46 GLI2 GLI3
21 prostate gland development GO:0030850 9.43 GLI2 GLI3
22 anatomical structure development GO:0048856 9.4 GLI2 GLI3
23 smoothened signaling pathway involved in dorsal/ventral neural tube patterning GO:0060831 9.37 GLI2 GLI3
24 spinal cord dorsal/ventral patterning GO:0021513 9.32 GLI2 GLI3
25 hindgut morphogenesis GO:0007442 9.26 GLI2 GLI3
26 smoothened signaling pathway involved in ventral spinal cord interneuron specification GO:0021775 9.16 GLI2 GLI3
27 smoothened signaling pathway involved in spinal cord motor neuron cell fate specification GO:0021776 8.96 GLI2 GLI3
28 tube development GO:0035295 8.62 GLI2 GLI3

Sources for Greig Cephalopolysyndactyly Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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