CJS
MCID: CLL036
MIFTS: 45

Culler-Jones Syndrome (CJS)

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

Aliases & Classifications for Culler-Jones Syndrome

MalaCards integrated aliases for Culler-Jones Syndrome:

Name: Culler-Jones Syndrome 56 12 52 58 73 29 6 15 39 71
Postaxial Polydactyly-Anterior Pituitary Anomalies-Facial Dysmorphism Syndrome 52 58
Cjs 56 73
Pallister-Hall Syndrome 2, Formerly; Phs2, Formerly 56
Pallister-Hall Syndrome 2, Formerly 56
Pallister-Hall Syndrome 2 73
Phs2, Formerly 56
Phs2 73

Characteristics:

Orphanet epidemiological data:

58
postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: infantile;

OMIM:

56
Miscellaneous:
variable expressivity
incomplete penetrance
variable phenotype

Inheritance:
autosomal dominant


HPO:

31
culler-jones syndrome:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity incomplete penetrance


Classifications:

Orphanet: 58  
Rare bone diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0080328
OMIM 56 615849
MeSH 43 D054975
ICD10 via Orphanet 33 Q87.8
Orphanet 58 ORPHA420584
UMLS 71 C4014479

Summaries for Culler-Jones Syndrome

NIH Rare Diseases : 52 Culler-Jones syndrome is a rare disease characterized by pituitary anomalies resulting in hypopituitarism , presence of extra fingers (polydactyly ) and unusual facial features. Symptoms related to the hypopituitarism may include abdominal pain, decreased appetite, short stature , delayed bone age , diabetes insipidus , slowed growth and sexual development, undescended testis (cryptorchidism) and small penis (hypogonadotropic hypogonadism ). Facial features include eyes that appear very close together (hypotelorism), cleft palate and cleft lip and a flat nose. The extra digits are usually located on the outside of the little fingers (post-axial polydactyly ). Brain imaging may show a small anterior pituitary gland . Culler-Jones syndrome is caused by changes (mutations ) in the GLI2 gene . Inheritance is autosomal dominant . Treatment may include replacement of the hormones that are lacking due to the hypopituitarism, and surgery to correct the extra digits and the facial defects. Mutations in the GLI2 gene can also cause a different condition known as holoprosencephaly-9 (HPE9) which is much more severe. That condition is characterized by a single-lobed brain structure and severe skull and facial defects.

MalaCards based summary : Culler-Jones Syndrome, also known as postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, is related to fibromatosis, gingival, with progressive deafness and holoprosencephaly. An important gene associated with Culler-Jones Syndrome is GLI2 (GLI Family Zinc Finger 2), and among its related pathways/superpathways are Hedgehog signaling pathway (KEGG) and Hedgehog signaling events mediated by Gli proteins. Affiliated tissues include pituitary, bone and eye, and related phenotypes are global developmental delay and midface retrusion

Disease Ontology : 12 A syndrome that is characterized by hypopituitarism, mainly growth hormone deficiency, and/or postaxial polydactyly and has material basis in autosomal dominant heterozygous mutation in the GLI2 gene on chromosome 2q14.

OMIM : 56 Culler-Jones syndrome (CJS) is an autosomal dominant disorder characterized by hypopituitarism, mainly growth hormone deficiency, and/or postaxial polydactyly. The phenotype is highly variable, and some patients may have midline facial defects and developmental delay. The disorder shows incomplete penetrance and variable expressivity (summary by Franca et al., 2010). (615849)

UniProtKB/Swiss-Prot : 73 Culler-Jones syndrome: An autosomal dominant disorder characterized by a wide range of clinical manifestations. Clinical features include hypothalamic hamartoma, pituitary dysfunction, central or postaxial polydactyly, and syndactyly. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia.

Related Diseases for Culler-Jones Syndrome

Diseases related to Culler-Jones Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 108)
# Related Disease Score Top Affiliating Genes
1 fibromatosis, gingival, with progressive deafness 10.3
2 holoprosencephaly 10.3
3 hypopituitarism 10.3
4 anxiety 10.2
5 conduct disorder 10.2
6 hemimelia 10.2 GLI3 GLI2
7 atherosclerosis susceptibility 10.1
8 autism spectrum disorder 10.1
9 viral hepatitis 10.1
10 orchitis 10.1
11 oropharynx cancer 10.1
12 48,xyyy 10.1
13 age-related hearing loss 10.1
14 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
15 hepatitis a 10.1
16 mood disorder 10.1
17 plague 10.1
18 scrapie 10.1
19 cytokine deficiency 10.1
20 chronic pain 10.1
21 anus, imperforate 10.0 GLI3 GLI2
22 pallister-hall syndrome 10.0 GLI3 GLI2
23 esophageal atresia 10.0 GLI3 GLI2
24 nephrolithiasis/osteoporosis, hypophosphatemic, 2 10.0 SMN2 SMN1
25 spinal muscular atrophy, type i 9.9 SMN2 SMN1
26 spinal muscular atrophy, type ii 9.9 SMN2 SMN1
27 proximal spinal muscular atrophy 9.9 SMN2 SMN1
28 anterior horn cell disease 9.9 SMN2 SMN1
29 amelogenesis imperfecta, type ia 9.9 SMN2 SMN1
30 spinal muscular atrophy, type iv 9.9 SMN2 SMN1
31 progressive muscular atrophy 9.9 SMN2 SMN1
32 alcohol dependence 9.9
33 creutzfeldt-jakob disease 9.9
34 attention deficit-hyperactivity disorder 9.9
35 renal cell carcinoma, nonpapillary 9.9
36 hypertension, essential 9.9
37 keratitis, hereditary 9.9
38 papillomatosis, confluent and reticulated 9.9
39 autism 9.9
40 lymphoma, hodgkin, classic 9.9
41 kuru 9.9
42 insulin-like growth factor i 9.9
43 yemenite deaf-blind hypopigmentation syndrome 9.9
44 branchiootic syndrome 1 9.9
45 lymphoma, non-hodgkin, familial 9.9
46 major depressive disorder 9.9
47 microvascular complications of diabetes 5 9.9
48 hearing loss, noise-induced 9.9
49 leptin deficiency or dysfunction 9.9
50 pulmonary hypertension 9.9

Graphical network of the top 20 diseases related to Culler-Jones Syndrome:



Diseases related to Culler-Jones Syndrome

Symptoms & Phenotypes for Culler-Jones Syndrome

Human phenotypes related to Culler-Jones Syndrome:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 midface retrusion 31 occasional (7.5%) HP:0011800
3 cleft palate 31 occasional (7.5%) HP:0000175
4 diabetes insipidus 31 occasional (7.5%) HP:0000873
5 cleft upper lip 31 occasional (7.5%) HP:0000204
6 hypotelorism 31 occasional (7.5%) HP:0000601
7 postaxial polydactyly 31 occasional (7.5%) HP:0100259
8 short stature 31 HP:0004322
9 cryptorchidism 31 HP:0000028
10 hypogonadism 31 HP:0000135
11 micropenis 31 HP:0000054
12 hypopituitarism 31 HP:0040075
13 anterior pituitary hypoplasia 31 HP:0010627
14 ectopic posterior pituitary 31 HP:0011755

Symptoms via clinical synopsis from OMIM:

56
Growth Height:
short stature

Endocrine Features:
hypopituitarism
hypogonadotropic hypogonadism
diabetes insipidus (in some patients)
combined pituitary hormone deficiency
low or absent growth hormone
more
Head And Neck Mouth:
cleft lip (in some patients)
cleft palate (in some patients)

Head And Neck Face:
midface hypoplasia (in some patients)

Skeletal Feet:
postaxial polydactyly (in some patients)

Genitourinary External Genitalia Male:
cryptorchidism
micropenis

Neurologic Central Nervous System:
anterior pituitary hypoplasia
ectopic posterior pituitary
thin pituitary stalk
delayed psychomotor development (in some patients)

Head And Neck Eyes:
hypotelorism (in some patients)

Skeletal Hands:
postaxial polydactyly (in some patients)

Clinical features from OMIM:

615849

MGI Mouse Phenotypes related to Culler-Jones Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.26 CCM2 GLI2 GLI3 SMN2
2 growth/size/body region MP:0005378 9.1 CCM2 GLI2 GLI3 SERPINI2 SMN2 TRAP1

Drugs & Therapeutics for Culler-Jones Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Integrating Services for Noncommunicable Diseases in Continuum of Care for Mothers and Children: a Cluster Randomized Control Trial in Myanmar Completed NCT03145155

Search NIH Clinical Center for Culler-Jones Syndrome

Genetic Tests for Culler-Jones Syndrome

Genetic tests related to Culler-Jones Syndrome:

# Genetic test Affiliating Genes
1 Culler-Jones Syndrome 29 GLI2

Anatomical Context for Culler-Jones Syndrome

MalaCards organs/tissues related to Culler-Jones Syndrome:

40
Pituitary, Bone, Eye, Brain, Heart, Testis, Thyroid

Publications for Culler-Jones Syndrome

Articles related to Culler-Jones Syndrome:

# Title Authors PMID Year
1
Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly. 56 6
20685856 2010
2
A previously unidentified amino-terminal domain regulates transcriptional activity of wild-type and disease-associated human GLI2. 56 6
15994174 2005
3
Hypopituitarism in association with postaxial polydactyly. 56 6
6726521 1984
4
Pathogenic mutations in GLI2 cause a specific phenotype that is distinct from holoprosencephaly. 56
24744436 2014
5
Relatively high frequency of non-synonymous GLI2 variants in patients with congenital hypopituitarism without holoprosencephaly. 56
22967285 2013
6
Clinical findings in patients with GLI2 mutations--phenotypic variability. 56
21204792 2012
7
Interaction of staphylococcal delta-toxin and synthetic analogues with erythrocytes and phospholipid vesicles. Biological and physical properties of the amphipathic peptides. 52
2474443 1989
8
A novel GLI2 mutation responsible for congenital hypopituitarism and polymalformation syndrome. 61
30583238 2019
9
A novel truncating variant of GLI2 associated with Culler-Jones syndrome impairs Hedgehog signalling. 61
30629636 2019
10
Human Malformation Syndromes of Defective GLI: Opposite Phenotypes of 2q14.2 (GLI2) and 7p14.2 (GLI3) Microdeletions and a GLIA/R Balance Model. 61
29298444 2017

Variations for Culler-Jones Syndrome

ClinVar genetic disease variations for Culler-Jones Syndrome:

6 (show all 22) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GLI2 GLI2, 1256TERSNV Pathogenic 139428
2 GLI2 NM_005270.4(GLI2):c.2362_2368del (p.Leu788Serfs)deletion Pathogenic 139429 rs587777455 2:121745849-121745855 2:120988273-120988279
3 GLI2 NM_005270.4(GLI2):c.2081_2084del (p.Leu694Argfs)deletion Pathogenic 139430 rs587777456 2:121743977-121743980 2:120986401-120986404
4 GLI2 NM_005270.4(GLI2):c.1138G>T (p.Glu380Ter)SNV Pathogenic 139431 rs374155310 2:121729595-121729595 2:120972019-120972019
5 GLI2 NM_005270.4(GLI2):c.322delG (p.Ala108Leufs)deletion Pathogenic 520904 rs1553471273 2:121708885-121708885 2:120951309-120951309
6 GLI2 NM_005270.4(GLI2):c.2314delA (p.Ser772Valfs)deletion Pathogenic 522404 rs1553478423 2:121745804-121745804 2:120988228-120988228
7 GLI2 NM_005270.4(GLI2):c.192dup (p.Asp65Terfs)duplication Pathogenic 573009 rs1388607733 2:121684978-121684979 2:120927402-120927403
8 GLI2 NM_005270.4(GLI2):c.1956+1G>ASNV Likely pathogenic 576501 rs1558937172 2:121742320-121742320 2:120984744-120984744
9 GLI2 NM_005270.4(GLI2):c.1120C>T (p.Arg374Cys)SNV Conflicting interpretations of pathogenicity 198528 rs200076785 2:121729577-121729577 2:120972001-120972001
10 GLI2 NM_005270.4(GLI2):c.451G>C (p.Ala151Pro)SNV Uncertain significance 541904 rs781771721 2:121709015-121709015 2:120951439-120951439
11 GLI2 NM_005270.4:c.677G>ASNV Uncertain significance 665586 2:121726323-121726323 2:120968747-120968747
12 GLI2 NM_005270.4:c.1178C>TSNV Uncertain significance 645913 2:121729635-121729635 2:120972059-120972059
13 GLI2 NM_005270.4:c.2158C>TSNV Uncertain significance 650369 2:121744055-121744055 2:120986479-120986479
14 GLI2 NM_005270.4:c.3893G>ASNV Uncertain significance 662958 2:121747383-121747383 2:120989807-120989807
15 GLI2 NM_005270.4(GLI2):c.2554G>A (p.Ala852Thr)SNV Uncertain significance 282738 rs751028726 2:121746044-121746044 2:120988468-120988468
16 GLI2 NM_005270.4(GLI2):c.1426G>C (p.Ala476Pro)SNV Uncertain significance 443998 rs772017351 2:121736067-121736067 2:120978491-120978491
17 GLI2 NM_005270.4(GLI2):c.4198G>T (p.Gly1400Cys)SNV Uncertain significance 475119 rs143914758 2:121747688-121747688 2:120990112-120990112
18 GLI2 NM_005270.4(GLI2):c.1541A>C (p.Tyr514Ser)SNV Uncertain significance 475118 rs1553477146 2:121740314-121740314 2:120982738-120982738
19 GLI2 NM_005270.4(GLI2):c.713T>C (p.Leu238Pro)SNV Uncertain significance 565646 rs1558923316 2:121726359-121726359 2:120968783-120968783
20 GLI2 NM_005270.4(GLI2):c.3048C>T (p.Asp1016=)SNV Benign/Likely benign 194220 rs140479803 2:121746538-121746538 2:120988962-120988962
21 GLI2 NM_005270.4(GLI2):c.1761G>A (p.Thr587=)SNV Benign/Likely benign 259719 rs61732852 2:121742124-121742124 2:120984548-120984548
22 GLI2 NM_005270.4(GLI2):c.3943C>T (p.Pro1315Ser)SNV Benign/Likely benign 95274 rs114376238 2:121747433-121747433 2:120989857-120989857

UniProtKB/Swiss-Prot genetic disease variations for Culler-Jones Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 GLI2 p.Pro608Leu VAR_071700 rs149800897
2 GLI2 p.Arg516Pro VAR_075214

Expression for Culler-Jones Syndrome

Search GEO for disease gene expression data for Culler-Jones Syndrome.

Pathways for Culler-Jones Syndrome

Pathways related to Culler-Jones Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.85 GLI3 GLI2
2 10.6 GLI3 GLI2
3
Show member pathways
9.9 GLI3 GLI2

GO Terms for Culler-Jones Syndrome

Cellular components related to Culler-Jones Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.67 SMN2 SMN1 GLI3 GLI2
2 axoneme GO:0005930 9.46 GLI3 GLI2
3 cytoplasmic ribonucleoprotein granule GO:0036464 9.43 SMN2 SMN1
4 Cajal body GO:0015030 9.4 SMN2 SMN1
5 ciliary tip GO:0097542 9.32 GLI3 GLI2
6 ciliary base GO:0097546 9.26 GLI3 GLI2
7 SMN-Sm protein complex GO:0034719 9.16 SMN2 SMN1
8 Gemini of coiled bodies GO:0097504 8.96 SMN2 SMN1
9 SMN complex GO:0032797 8.62 SMN2 SMN1

Biological processes related to Culler-Jones Syndrome according to GeneCards Suite gene sharing:

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 heart development GO:0007507 9.75 GLI3 GLI2 CCM2
2 in utero embryonic development GO:0001701 9.72 GLI3 GLI2 CCM2
3 lung development GO:0030324 9.64 GLI3 GLI2
4 smoothened signaling pathway GO:0007224 9.63 GLI3 GLI2
5 odontogenesis of dentin-containing tooth GO:0042475 9.63 GLI3 GLI2
6 pattern specification process GO:0007389 9.62 GLI3 GLI2
7 embryonic digit morphogenesis GO:0042733 9.62 GLI3 GLI2
8 inner ear development GO:0048839 9.61 GLI3 CCM2
9 neural tube development GO:0021915 9.61 GLI3 GLI2
10 anatomical structure development GO:0048856 9.6 GLI3 GLI2
11 dorsal/ventral pattern formation GO:0009953 9.59 GLI3 GLI2
12 mammary gland development GO:0030879 9.58 GLI3 GLI2
13 developmental growth GO:0048589 9.57 GLI3 GLI2
14 spliceosomal snRNP assembly GO:0000387 9.56 SMN2 SMN1
15 branching morphogenesis of an epithelial tube GO:0048754 9.54 GLI3 GLI2
16 spliceosomal complex assembly GO:0000245 9.52 SMN2 SMN1
17 proximal/distal pattern formation GO:0009954 9.51 GLI3 GLI2
18 import into nucleus GO:0051170 9.49 SMN2 SMN1
19 spinal cord motor neuron differentiation GO:0021522 9.48 GLI3 GLI2
20 anatomical structure formation involved in morphogenesis GO:0048646 9.46 GLI3 GLI2
21 embryonic digestive tract development GO:0048566 9.43 GLI3 GLI2
22 DNA-templated transcription, termination GO:0006353 9.4 SMN2 SMN1
23 smoothened signaling pathway involved in dorsal/ventral neural tube patterning GO:0060831 9.37 GLI3 GLI2
24 spinal cord dorsal/ventral patterning GO:0021513 9.32 GLI3 GLI2
25 hindgut morphogenesis GO:0007442 9.26 GLI3 GLI2
26 tube development GO:0035295 9.16 GLI3 GLI2
27 smoothened signaling pathway involved in spinal cord motor neuron cell fate specification GO:0021776 8.96 GLI3 GLI2
28 smoothened signaling pathway involved in ventral spinal cord interneuron specification GO:0021775 8.62 GLI3 GLI2

Sources for Culler-Jones Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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