Craniosynostosis (CSO)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Infectious diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Craniosynostosis

MalaCards integrated aliases for Craniosynostosis:

Name: Craniosynostosis 11 19 52 58 75 53 14 38 71 31 33
Premature Closure of Cranial Sutures 11 33
Craniosynostosis Syndrome 28 5
Craniostenosis 19 33
Congenital Ossification of Sutures of Skull 33
Congenital Ossification of Cranial Sutures 33
Congenital Imperfect Closure Skull 33
Premature Closure Cranium Sutures 33
Deficiency of Craniofacial Axis 33
Imperfect Fusion of Skull 33
Imperfect Closure Skull 33
Craniosynostoses 43
Craniostosis 33
Cso 19



Autosomal dominant,Autosomal recessive,X-linked recessive 58


1-5/10000 (France, Australia, United States) 58

Age Of Onset:

Infancy,Neonatal 58


Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis

External Ids:

Disease Ontology 11 DOID:2340
MeSH 43 D003398
NCIt 49 C84655
SNOMED-CT 68 205414007
ICD10 31 Q75.0
MESH via Orphanet 44 D003398
ICD10 via Orphanet 32 Q75.0
UMLS via Orphanet 72 C0010278
Orphanet 58 ORPHA1531
UMLS 71 C0010278

Summaries for Craniosynostosis

GARD: 19 Craniosynostosis is the premature closure of one or more of the joints that connect the bones of a baby's skull (cranial sutures). Normally, the bones remain separate until about age 2, while the brain is growing. They then fuse together and stay connected throughout life. The closure is premature when it occurs before brain growth is complete. Symptoms and severity vary depending on how many sutures close prematurely. For example, if only one closes prematurely (which is most common), brain growth may continue in other parts of the skull, leading only to an abnormally-shaped skull and no other health problems or complications. If multiple sutures close prematurely, brain growth can be restricted. This can lead to increased pressure in the skull, impaired brain development, seizures, blindness, and/or intellectual disability. Craniosynostosis may occur as a single abnormality (isolated Craniosynostosis) or it may occur as one feature of one of many syndromes. Most cases of isolated Craniosynostosis occur randomly (sporadically) and have no known cause. In some cases, isolated Craniosynostosis is due to a genetic change in any of several genes, with autosomal dominant inheritance. When Craniosynostosis is a feature of a larger syndrome (syndromic Craniosynostosis), the cause and inheritance pattern depend on the syndrome the person has. However, most syndromic causes of Craniosynostosis are autosomal dominant. Craniosynostosis can also be associated with a metabolic disease such as rickets, or hyperthyroidism. However, not all children with Craniosynostosis will need surgery. Children who have surgery and are otherwise healthy generally do not experience long-term complications, especially when only one suture is involved.

MalaCards based summary: Craniosynostosis, also known as premature closure of cranial sutures, is related to muenke syndrome and jackson-weiss syndrome. An important gene associated with Craniosynostosis is FGFR2 (Fibroblast Growth Factor Receptor 2), and among its related pathways/superpathways are Breast cancer pathway and Endochondral ossification. The drugs Tranexamic acid and Antifibrinolytic Agents have been mentioned in the context of this disorder. Affiliated tissues include Bone, and related phenotypes are Decreased viability in pancreas lineage and nervous system

NINDS: 52 Craniosynostosis is a birth defect of the skull characterized by the premature closure of one or more of the fibrous joints between the bones of the skull (called the cranial sutures) before brain growth is complete. Closure of a single suture is most common. Normally the skull expands uniformly to accommodate the growth of the brain; premature closure of a single suture restricts the growth in that part of the skull and promotes growth in other parts of the skull where sutures remain open. This results in a misshapen skull but does not prevent the brain from expanding to a normal volume. However, when many sutures close prematurely, the skull cannot expand to accommodate the growing brain, which leads to increased pressure within the skull and impaired development of the brain. Craniosynostosis can be gene-linked or caused by metabolic diseases (such as rickets )or an overactive thyroid. Some cases are associated with other disorders such as microcephaly (abnormally small head) and hydrocephalus (excessive accumulation of cerebrospinal fluid in the brain). The first sign of craniosynostosis is an abnormally shaped skull. Other features can include signs of increased intracranial pressure, developmental delays, or impaired cognitive development, which are caused by constriction of the growing brain. Seizures and blindness may also occur.

Orphanet: 58 Craniosynostosis is defined as the premature fusion of one or more cranial sutures leading to secondary distortion of skull shape resulting in skull deformities with a variable presentation. Craniosynostosis may occur in an isolated setting or as part of a syndrome.

Disease Ontology: 11 A synostosis that results in premature fusion located in skull.

Wikipedia: 75 Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infant's skull... more...

Related Diseases for Craniosynostosis

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 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 813)
# Related Disease Score Top Affiliating Genes
1 muenke syndrome 33.3 TWIST1 TCF12 MSX2 FGFR3 FGFR2 FGFR1
2 jackson-weiss syndrome 33.1 TWIST1 MSX2 FGFR3 FGFR2 FGFR1
3 beare-stevenson cutis gyrata syndrome 33.0 FGFR3 FGFR2 FGFR1
4 pfeiffer syndrome 32.8 TWIST1 MSX2 FGFR3 FGFR2 FGFR1
5 apert syndrome 32.8 TWIST1 TCF12 MSX2 MEGF8 GLI3 FGFR3
6 saethre-chotzen syndrome 32.7 TWIST1 TCF12 RECQL4 MSX2 GLI3 FGFR3
7 crouzon syndrome 32.7 TWIST1 TCF12 NPR2 MSX2 FGFR3 FGFR2
8 carpenter syndrome 1 32.7 TWIST1 MSX2 MEGF8 GLI3 FGFR3 FGFR2
9 non-syndromic bicoronal craniosynostosis 32.6 TWIST1 TCF12 FGFR3
10 osteoglophonic dysplasia 32.5 FGFR3 FGFR2 FGFR1
11 craniofrontonasal syndrome 32.5 TCF12 MSX2 FGFR2
12 antley-bixler syndrome 32.4 FGFR3 FGFR2 FGFR1
13 synostosis 32.3 TWIST1 TCF12 SMAD6 RECQL4 MSX2 GLI3
14 chromosome 2q35 duplication syndrome 32.3 MSX2 MEGF8 GLI3 GLI2 FGFR3 FGFR2
15 crouzon syndrome with acanthosis nigricans 32.1 FGFR3 FGFR2
16 plagiocephaly 32.0 SMAD6 FGFR3 FGFR2 FGFR1
17 lacrimoauriculodentodigital syndrome 31.9 FGFR3 FGFR2 FGFR1
18 hypertelorism 31.4 TWIST1 GLI3 FGFR2
19 cleft palate, isolated 31.2 TWIST1 MSX2 GLI3 GLI2 FGFR3 FGFR2
20 achondroplasia 31.1 MSX2 FGFR3 FGFR2 FGFR1
21 dysostosis 31.1 TWIST1 RECQL4 MSX2 MAN2B1 GLI3 FGFR3
22 parietal foramina 31.0 TWIST1 MSX2 FGFR3
23 hemifacial hyperplasia 31.0 FGFR3 FGFR2
24 osteochondrodysplasia 30.9 TRPS1 NPR2 MSX2 FGFR3 FGFR2 FGFR1
25 hypertelorism, microtia, facial clefting syndrome 30.9 TWIST1 MSX2 FGFR3 FGFR2 FGFR1
26 thanatophoric dysplasia, type i 30.9 NPR2 FGFR3 FGFR2 FGFR1
27 charge syndrome 30.9 SOX11 GLI3 FGFR1
28 ptosis 30.8 ZNF462 TWIST1 TCF20 GLI3
29 polydactyly 30.7 TWIST1 SMAD6 MEGF8 GLI3 GLI2 FGFR2
30 tooth agenesis 30.7 TFAP2B MSX2 GLI3 FGFR2 FGFR1
31 holoprosencephaly 30.7 TWIST1 GLI3 GLI2 FGFR3 FGFR2 FGFR1
32 hypochondroplasia 30.7 NPR2 FGFR3 FGFR2 FGFR1
33 cleidocranial dysplasia 1 30.6 MSX2 FGFR3 FGFR2
34 achondroplasia, severe, with developmental delay and acanthosis nigricans 30.4 NPR2 FGFR3 FGFR2 FGFR1
35 isolated growth hormone deficiency, type ia 30.3 NPR2 FGFR3 FGFR2
36 exposure keratitis 30.1 TCF12 FGFR2
37 simpson-golabi-behmel syndrome, type 1 29.7 MEGF8 GPC4
38 shprintzen-goldberg craniosynostosis syndrome 11.6
39 craniosynostosis 2 11.6
40 baller-gerold syndrome 11.6
41 craniosynostosis 7 11.5
42 craniosynostosis 1 11.5
43 hunter-mcalpine craniosynostosis syndrome 11.5
44 scarf syndrome 11.5
45 cdags syndrome 11.5
46 craniosynostosis 5 11.5
47 craniosynostosis and dental anomalies 11.4
48 craniosynostosis 6 11.4
49 craniosynostosis 4 11.4
50 craniosynostosis philadelphia type 11.4

Graphical network of the top 20 diseases related to Craniosynostosis:

Diseases related to Craniosynostosis

Symptoms & Phenotypes for Craniosynostosis

GenomeRNAi Phenotypes related to Craniosynostosis according to GeneCards Suite gene sharing:

# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 10.18 FGFR1 FGFR2 FGFR3 GLI2 GLI3 GPC4
2 no effect GR00402-S-2 10.18 FGFR1 FGFR2 FGFR3 GLI2 GLI3 GPC4
3 Decreased viability in pancreas lineage GR00235-A 8.96 TFAP2B TWIST1

MGI Mouse Phenotypes related to Craniosynostosis:

45 (show all 22)
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 10.5 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
2 growth/size/body region MP:0005378 10.5 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
3 homeostasis/metabolism MP:0005376 10.47 FGFR1 FGFR2 FGFR3 GLI2 GLI3 GPC4
4 limbs/digits/tail MP:0005371 10.39 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
5 digestive/alimentary MP:0005381 10.36 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
6 craniofacial MP:0005382 10.34 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
7 endocrine/exocrine gland MP:0005379 10.31 FGFR1 FGFR2 GLI2 GLI3 KAT6A MAN2B1
8 behavior/neurological MP:0005386 10.31 FGFR1 FGFR2 FGFR3 GLI2 GPC4 KAT6A
9 muscle MP:0005369 10.28 FGFR1 FGFR2 GLI2 MAN2B1 MEGF8 MSX2
10 cardiovascular system MP:0005385 10.27 FGFR1 FGFR2 GLI3 KAT6A MAN2B1 MEGF8
11 embryo MP:0005380 10.26 FGFR1 FGFR2 GLI2 GLI3 KAT6A MEGF8
12 cellular MP:0005384 10.26 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
13 normal MP:0002873 10.21 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
14 skeleton MP:0005390 10.2 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
15 renal/urinary system MP:0005367 10.19 FGFR1 FGFR2 FGFR3 GLI3 MAN2B1 MEGF8
16 immune system MP:0005387 10.18 FGFR1 FGFR2 FGFR3 KAT6A MAN2B1 MEGF8
17 hearing/vestibular/ear MP:0005377 10.1 FGFR1 FGFR2 FGFR3 GLI2 GLI3 MAN2B1
18 vision/eye MP:0005391 10.03 FGFR1 FGFR2 FGFR3 GLI2 GLI3 MAN2B1
19 respiratory system MP:0005388 10.02 FGFR2 FGFR3 GLI2 GLI3 MEGF8 NPR2
20 hematopoietic system MP:0005397 9.97 FGFR1 FGFR2 FGFR3 GPC4 KAT6A MAN2B1
21 mortality/aging MP:0010768 9.91 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A
22 integument MP:0010771 9.47 FGFR1 FGFR2 FGFR3 GLI2 GLI3 KAT6A

Drugs & Therapeutics for Craniosynostosis

Drugs for Craniosynostosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 23)
# Name Status Phase Clinical Trials Cas Number PubChem Id
Tranexamic acid Approved Phase 4 1197-18-8 5526
2 Antifibrinolytic Agents Phase 4
3 Hemostatics Phase 4
4 Coagulants Phase 4
Aminocaproic acid Approved, Investigational Phase 2 60-32-2 564
Levobupivacaine Approved, Investigational 27262-47-1 92253
Acetaminophen Approved 103-90-2 1983
Tramadol Approved, Investigational 27203-92-5 33741 5523
Ferrous fumarate Approved 141-01-5
Iron Approved 7439-89-6 29936
Cholecalciferol Approved, Nutraceutical, Vet_approved 67-97-0, 1406-16-2 5280795 10883523
Imidacloprid Vet_approved 105827-78-9 86418
13 Analgesics
14 Calcium, Dietary
bilirubin 635-65-4 5280352
16 Trace Elements
Epoetin Alfa
18 Chrysarobin
19 Micronutrients
20 Vitamins
21 Calciferol
22 Anesthetics
Calcium Nutraceutical 7440-70-2 271

Interventional clinical trials:

(show all 37)
# Name Status NCT ID Phase Drugs
1 The Efficacy and Population Pharmacokinetics/ Pharmacogenomics of a Reduced Dose of Tranexamic Acid for Craniosynostosis Surgery Completed NCT02188576 Phase 4 high dose TXA;Low dose TXA
2 Tranexamic Acid for the Reduction of Allogeneic Blood Exposure in Infants and Children Having Craniofacial Surgery Terminated NCT00722436 Phase 4 Tranexamic acid;saline
3 Comparison of Allogenix Plus Demineralized Bone Matrix and Autogenous Bone Dust Versus Autogenous Bone Dust Alone in Ossification of Small Calvarial Defects, a Pilot Study. Withdrawn NCT01006148 Phase 4
4 Blood Loss and Transfusion Requirement in Infants Treated With Tranexamic Acid Undergoing Craniosynostosis Reconstruction: A Randomized Placebo-Controlled Double Blind Study of Low and High Dose Therapy Suspended NCT01094977 Phase 3 Tranexamic Acid;Saline Placebo
5 Efficacy of ε-Aminocaproic Acid (EACA) in Children Undergoing Craniofacial Reconstruction Surgery Active, not recruiting NCT02229968 Phase 2 Amicar (ε-aminocaproic acid);normal saline
6 Pharmacokinetics of Epsilon-Aminocaproic Acid in Children Undergoing Craniofacial Reconstruction Surgery Completed NCT00912119 Phase 1 Epsilon-Aminocaproic Acid
7 The Effect of Gender on the Consumption of Pain Medication in Infants Undergoing Craniosynostosis Repair or Untethering of Cord in ITU Unknown status NCT01996163
8 Genetic Analysis of Craniosynostosis, Philadelphia Type (OMIM 601222) Completed NCT00367796
9 MRI for Non-invasive Evaluation of Brain Stress Completed NCT01898650
10 Osteogenic Profiling of Tissue From Children With Craniosynostosis Completed NCT00773643
11 Craniosynostosis: How to Improve the Diagnosis and Assist Patients and Their Families? Completed NCT02287805
12 Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis) Completed NCT00106977
13 Neurobehavioral Correlates of Craniosynostosis Completed NCT00077831
14 Effect of Tranexamic Acid Based on Pharmacokinetics in Pediatric Patients Undergoing Craniosynostosis Surgery: Randomized Controlled Trial Completed NCT02180321 Tranexamic Acid;normal saline
15 The Scalp Block for Postoperative Pain Control in Craniosynostosis Surgery: a Case Control Study Completed NCT04133467
16 Changes of Optic Nerve Sheath Diameter in Modified Prone Position in Craniosynostosis Children Completed NCT03131245
17 The Affect of Radiated Versus Non-Irradiated Blood on Extracellular Potassium Levels in Infants Undergoing Craniosynostosis Repair Completed NCT02483702
18 Investigation of Anthropometric Properties of Babies With Craniosynostosis Completed NCT04827524
19 Nautilus: Dynamic Craniotomy; New Surgical Technique and Preliminary Results Completed NCT01672619
20 Effectiveness of Ottobock Helmet Therapy in Infants With Plagiocephaly, Brachycephaly or Combination of Both and Parents' Satisfaction Completed NCT05154175
21 Effectiveness of Tortle Midliner Positioning System on the Prevention and Treatment of Cranial Molding Deformities in Preterm Infants Completed NCT02366936
22 Craniosynostosis Network Recruiting NCT03025763
23 Endoscopic Strip Craniectomy for Treatment of Isolated, Non-syndromic Sagittal Craniosynostosis Recruiting NCT04721769
24 Comparison of the Rate of Preoperative Haemoglobin After Administration of Epoetin Alpha Associated With an Oral Medical Supplementation Versus Intravenous Before Surgery of Craniosynostosis at the Child Recruiting NCT03231085 Ferrous fumarate or ferrostrane
25 Effect of Burosumab and 1-25 (OH) Vitamin D on Human Osteoblasts From Patients Requiring Craniosynostosis Surgery for Idiopathic Reason or Due to Hypophosphatemic Rickets (HR) Recruiting NCT04159675
26 Clinical Feasibility Study of Preoperative Surgical Planning for Craniosynostosis Procedures Recruiting NCT03812159
27 A Monocentric, Prospective Clinical Study to Evaluation of Cerebral Oxygen Saturation by Near InfraRed Spectroscopy (NIRS) in Children With Craniosynostosis Recruiting NCT04086056
28 Neurodevelopmental Outcomes in Craniosynostosis Repair Recruiting NCT04072783
29 Craniofacial Imaging With 3D MRI: an Alternative to Ionising Radiation Recruiting NCT04695938
30 Bedside Resources to Gauge Intravascular Volume Status in Hypovolemic Infants in the Operating Room Recruiting NCT03915587
31 GROWing Up With Rare GENEtic Syndromes ….When Children With Complex Genetic Syndromes Reach Adult Age Recruiting NCT04463316
32 Comparative Analysis of Zero Echo-time MRI and CT for Pediatric Craniosynostosis Enrolling by invitation NCT04704284
33 Craniosynostosis : Surgical Treatment Modalities and Outcome Not yet recruiting NCT05511168
34 A Pilot, Prospective Study of Myelin Imaging Changes in Patients With Neurosurgical Diseases Terminated NCT03698838
35 Cranial Cup Use for the Prevention of Positional Head Shape Deformity in the NICU Terminated NCT01218087
36 Endoscopic Treatment for Isolated, Single Suture Craniosynostosis Withdrawn NCT00769847
37 Prospective Study to Evaluate Effectiveness of the Hanger Helmet vs the P Pod Helmet in Improving the Head and Face Symmetry Withdrawn NCT02561728

Search NIH Clinical Center for Craniosynostosis

Cochrane evidence based reviews: craniosynostoses

Genetic Tests for Craniosynostosis

Genetic tests related to Craniosynostosis:

# Genetic test Affiliating Genes
1 Craniosynostosis Syndrome 28

Anatomical Context for Craniosynostosis

Organs/tissues related to Craniosynostosis:

FMA: Skull
MalaCards : Bone, Brain, Thyroid, Eye, Fetal Brain, Heart, Skin
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Craniosynostosis:
# Tissue Anatomical CompartmentCell Relevance
1 Bone Rostral Sutures Fusing Suture Cells Affected by disease
2 Bone Rostral Sutures Presumptive Suture Cells Affected by disease
3 Bone Facial Sutures Presumptive Suture Cells Affected by disease
4 Bone Facial Sutures Suture Cells Affected by disease
5 Bone Rostral Sutures Suture Cells Affected by disease

Publications for Craniosynostosis

Articles related to Craniosynostosis:

(show top 50) (show all 5422)
# Title Authors PMID Year
NGS targeted screening of 100 Scandinavian patients with coronal synostosis. 62 5
31837199 2020
Mutations in TFAP2B and previously unimplicated genes of the BMP, Wnt, and Hedgehog pathways in syndromic craniosynostosis. 62 5
31292255 2019
Single suture craniosynostosis: Identification of rare variants in genes associated with syndromic forms. 62 5
29168297 2018
Co-occurrence of frameshift mutations in SMAD6 and TCF12 in a child with complex craniosynostosis. 62 5
30038786 2018
Clinical genetics of craniosynostosis. 62 5
28914635 2017
Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants. 62 5
25271085 2015
Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients. 62 5
24127277 2013
Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization. 62 5
23063620 2012
A gain-of-function mutation of Fgfr2c demonstrates the roles of this receptor variant in osteogenesis. 62 5
15316116 2004
Constitutive receptor activation by Crouzon syndrome mutations in fibroblast growth factor receptor (FGFR)2 and FGFR2/Neu chimeras. 62 5
8755573 1996
First-trimester prenatal diagnosis of Crouzon syndrome. 62 5
8650126 1996
Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. 62 5
7987400 1994
New insights into genotype-phenotype correlation for GLI3 mutations. 5
24736735 2015
Expanded mutational spectrum of the GLI3 gene substantiates genotype-phenotype correlations. 5
22903559 2012
Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation. 5
22558232 2012
Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome: five cases with intragenic mutations or complete deletions of GLI3. 5
21326280 2011
Analysis of a gain-of-function FGFR2 Crouzon mutation provides evidence of loss of function activity in the etiology of cleft palate. 5
20133659 2010
A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases. 5
17803937 2007
Saethre-Chotzen syndrome: a case report. 53 62
19860490 2010
Increased EFG- and PDGFalpha-receptor signaling by mutant FGF-receptor 2 contributes to osteoblast dysfunction in Apert craniosynostosis. 53 62
20124286 2010
Dura in the pathogenesis of syndromic craniosynostosis: fibroblast growth factor receptor 2 mutations in dural cells promote osteogenic proliferation and differentiation of osteoblasts. 53 62
20489451 2010
Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2(+P253R) mice. 53 62
20175913 2010
New insight on FGFR3-related chondrodysplasias molecular physiopathology revealed by human chondrocyte gene expression profiling. 53 62
19898608 2009
Q289P mutation in the FGFR2 gene: first report in a patient with type 1 Pfeiffer syndrome. 53 62
19066959 2009
Cleft palate in Pfeiffer syndrome. 53 62
19816260 2009
Medical treatment of craniosynostosis: recombinant Noggin inhibits coronal suture closure in the rat craniosynostosis model. 53 62
19627528 2009
Boy with pseudohypoparathyroidism type 1a caused by GNAS gene mutation (deltaN377), Crouzon-like craniosynostosis, and severe trauma-induced bleeding. 53 62
19530187 2009
Reoperation for intracranial hypertension in TWIST1-confirmed Saethre-Chotzen syndrome: a 15-year review. 53 62
19483581 2009
Craniosynostosis in patients with Noonan syndrome caused by germline KRAS mutations. 53 62
19396835 2009
Identification of novel fibroblast growth factor receptor 3 gene mutations in actinic cheilitis and squamous cell carcinoma of the lip. 53 62
19327639 2009
Rare mutations of FGFR2 causing apert syndrome: identification of the first partial gene deletion, and an Alu element insertion from a new subfamily. 53 62
18726952 2009
FGFR2 as a molecular target in endometrial cancer. 53 62
19243295 2009
Ex vivo Noggin gene therapy inhibits bone formation in a mouse model of postoperative resynostosis. 53 62
19182668 2009
Craniosynostosis, hydrocephalus, Chiari I malformation and radioulnar synostosis: probably a new syndrome. 53 62
19022412 2009
Genetics of craniosynostosis: review of the literature. 53 62
20108486 2009
Apert syndrome: report of a case with emphasis on craniofacial and genetic features. 53 62
19186770 2008
A Pro253Arg mutation in fibroblast growth factor receptor 2 (Fgfr2) causes skeleton malformation mimicking human Apert syndrome by affecting both chondrogenesis and osteogenesis. 53 62
18242159 2008
The natural history of patients treated for FGFR3-associated (Muenke-type) craniosynostosis. 53 62
18317141 2008
Adverse facial edema associated with off-label use of recombinant human bone morphogenetic protein-2 in cranial reconstruction for craniosynostosis. Case report. 53 62
18352773 2008
FGF-2 signaling induces downregulation of TAZ protein in osteoblastic MC3T3-E1 cells. 53 62
18067853 2008
Genetics of craniosynostosis: genes, syndromes, mutations and genotype-phenotype correlations. 53 62
18391498 2008
Roles of FGFR2 and twist in human craniosynostosis: insights from genetic mutations in cranial osteoblasts. 53 62
18391499 2008
P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia. 53 62
18493134 2008
Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature. 53 62
18000976 2007
Craniosynostosis associated with distal 5q-trisomy: further evidence that extra copy of MSX2 gene leads to craniosynostosis. 53 62
17955513 2007
Syndromic craniosynostosis due to complex chromosome 5 rearrangement and MSX2 gene triplication. 53 62
18000908 2007
Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes. 53 62
17525745 2007
RNA interference and inhibition of MEK-ERK signaling prevent abnormal skeletal phenotypes in a mouse model of craniosynostosis. 53 62
17694057 2007
Clinical dividends from the molecular genetic diagnosis of craniosynostosis. 53 62
17621648 2007
An 11q11-q13.3 duplication, including FGF3 and FGF4 genes, in a patient with syndromic multiple craniosynostoses. 53 62
17632770 2007

Variations for Craniosynostosis

ClinVar genetic disease variations for Craniosynostosis:

5 (show top 50) (show all 300)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ZNF462 NM_021224.6(ZNF462):c.3787C>T (p.Arg1263Ter) SNV Pathogenic
402116 rs1060499549 GRCh37: 9:109689980-109689980
GRCh38: 9:106927699-106927699
2 ZNF462 NM_021224.6(ZNF462):c.4263del (p.Glu1422fs) DEL Pathogenic
402117 rs1060499551 GRCh37: 9:109690455-109690455
GRCh38: 9:106928174-106928174
3 ZNF462 NM_021224.6(ZNF462):c.2979_2980delinsA (p.Val994fs) INDEL Pathogenic
402118 rs1060499550 GRCh37: 9:109689172-109689173
GRCh38: 9:106926891-106926892
4 TCF12 NM_207037.2(TCF12):c.1643_1647del (p.Glu548fs) DEL Pathogenic
1344584 GRCh37: 15:57555366-57555370
GRCh38: 15:57263168-57263172
5 MEGF8 NM_001271938.2(MEGF8):c.5073del (p.Phe1692fs) DEL Pathogenic
1162320 GRCh37: 19:42862352-42862352
GRCh38: 19:42358200-42358200
6 TCF20 NM_001378418.1(TCF20):c.1166_1167del (p.Leu389fs) MICROSAT Pathogenic
1172629 GRCh37: 22:42610145-42610146
GRCh38: 22:42214139-42214140
7 GLI3 NM_000168.6(GLI3):c.368-459_473+494del DEL Pathogenic
1177290 GRCh37: 7:42115857-42116915
GRCh38: 7:42076258-42077316
8 FGFR3 NM_000142.5(FGFR3):c.1172C>A (p.Ala391Glu) SNV Pathogenic
16329 rs28931615 GRCh37: 4:1806153-1806153
GRCh38: 4:1804426-1804426
9 FGFR3 NM_000142.5(FGFR3):c.598C>T (p.Arg200Cys) SNV Pathogenic
287276 rs886043613 GRCh37: 4:1803246-1803246
GRCh38: 4:1801519-1801519
10 MAN2B1 NM_000528.4(MAN2B1):c.215_216del (p.His72fs) DEL Pathogenic
1065630 GRCh37: 19:12776563-12776564
GRCh38: 19:12665749-12665750
11 FGFR2 NM_000141.5(FGFR2):c.1032G>A (p.Ala344_Gly345=) SNV Pathogenic
13268 rs121918491 GRCh37: 10:123276885-123276885
GRCh38: 10:121517371-121517371
12 FGFR3 NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg) SNV Pathogenic
16340 rs4647924 GRCh37: 4:1803571-1803571
GRCh38: 4:1801844-1801844
13 FGFR2 NM_000141.5(FGFR2):c.1025G>A (p.Cys342Tyr) SNV Pathogenic
13263 rs121918487 GRCh37: 10:123276892-123276892
GRCh38: 10:121517378-121517378
14 SMAD6 NM_005585.5(SMAD6):c.465_471del (p.Gly156fs) MICROSAT Pathogenic
638816 rs958818801 GRCh37: 15:66996051-66996057
GRCh38: 15:66703713-66703719
15 FGFR2 NM_000141.5(FGFR2):c.1570A>G (p.Thr524Ala) SNV Likely Pathogenic
376749 rs1057520044 GRCh37: 10:123258111-123258111
GRCh38: 10:121498597-121498597
16 FGFR2 NM_000141.5(FGFR2):c.1694A>C (p.Glu565Ala) SNV Likely Pathogenic
13294 rs121918506 GRCh37: 10:123256215-123256215
GRCh38: 10:121496701-121496701
17 FGFR2 NM_000141.5(FGFR2):c.1913A>C (p.Asn638Thr) SNV Likely Pathogenic
376750 rs777169135 GRCh37: 10:123247578-123247578
GRCh38: 10:121488064-121488064
18 KAT6A NM_006766.5(KAT6A):c.3661G>T (p.Glu1221Ter) SNV Likely Pathogenic
280246 rs139494583 GRCh37: 8:41792077-41792077
GRCh38: 8:41934559-41934559
19 GRIN2B NM_000834.5(GRIN2B):c.2216T>G (p.Met739Arg) SNV Likely Pathogenic
523381 rs1555103652 GRCh37: 12:13722907-13722907
GRCh38: 12:13569973-13569973
20 TRPS1 NM_014112.5(TRPS1):c.1230G>A (p.Trp410Ter) SNV Likely Pathogenic
373946 rs1057518791 GRCh37: 8:116616966-116616966
GRCh38: 8:115604739-115604739
21 MEGF8 NM_001271938.2(MEGF8):c.7970_7972del (p.Ser2657del) DEL Likely Pathogenic
1164007 GRCh37: 19:42880357-42880359
GRCh38: 19:42376205-42376207
22 SOX11 NM_003108.4(SOX11):c.191G>A (p.Arg64His) SNV Likely Pathogenic
1344679 GRCh37: 2:5833044-5833044
GRCh38: 2:5692912-5692912
23 GLI2 NM_001374353.1(GLI2):c.1600G>A (p.Ala534Thr) SNV Likely Pathogenic
1344680 GRCh37: 2:121740424-121740424
GRCh38: 2:120982848-120982848
24 CTNNA1 NM_001903.5(CTNNA1):c.2572_2586dup (p.Ser858_Lys862dup) DUP Likely Pathogenic
1344681 GRCh37: 5:138269627-138269628
GRCh38: 5:138933938-138933939
25 TFAP2B NM_003221.4(TFAP2B):c.3G>A (p.Met1Ile) SNV Likely Pathogenic
1344682 GRCh37: 6:50786607-50786607
GRCh38: 6:50818894-50818894
26 TFAP2B NM_003221.4(TFAP2B):c.601+2T>A SNV Likely Pathogenic
1344683 GRCh37: 6:50796394-50796394
GRCh38: 6:50828681-50828681
27 TFAP2B NM_003221.4(TFAP2B):c.827A>G (p.Lys276Arg) SNV Likely Pathogenic
1344684 GRCh37: 6:50805693-50805693
GRCh38: 6:50837980-50837980
28 TFAP2B NM_003221.4(TFAP2B):c.1144C>T (p.Arg382Ter) SNV Likely Pathogenic
1344685 GRCh37: 6:50810866-50810866
GRCh38: 6:50843153-50843153
29 GPC4 NM_001448.3(GPC4):c.455del (p.Val152fs) DEL Likely Pathogenic
1344686 GRCh37: X:132458429-132458429
GRCh38: X:133324401-133324401
30 CNPY2 NM_014255.7(CNPY2):c.46_50del (p.Gly16fs) DEL Likely Pathogenic
1679340 GRCh37: 12:56708952-56708956
GRCh38: 12:56315168-56315172
31 TCF12 NM_207037.2(TCF12):c.1769del (p.Asp589_Leu590insTer) DEL Likely Pathogenic
691564 rs1597816045 GRCh37: 15:57565249-57565249
GRCh38: 15:57273051-57273051
32 TCF12 NM_207037.2(TCF12):c.1606del (p.Thr536fs) DEL Likely Pathogenic
691565 rs1597730335 GRCh37: 15:57555332-57555332
GRCh38: 15:57263134-57263134
33 NPR2 NM_003995.4(NPR2):c.779A>T (p.Glu260Val) SNV Likely Pathogenic
373988 rs757744435 GRCh37: 9:35794006-35794006
GRCh38: 9:35794009-35794009
34 NPR2 NM_003995.4(NPR2):c.2162_2172del (p.Ser721fs) DEL Likely Pathogenic
373987 rs1057518817 GRCh37: 9:35805941-35805951
GRCh38: 9:35805944-35805954
35 FGFR1 NM_023110.3(FGFR1):c.*1965G>A SNV Uncertain Significance
362861 rs886062907 GRCh37: 8:38269181-38269181
GRCh38: 8:38411663-38411663
36 FGFR1 NM_023110.3(FGFR1):c.*2407C>T SNV Uncertain Significance
362855 rs758524862 GRCh37: 8:38268739-38268739
GRCh38: 8:38411221-38411221
37 FGFR1 NM_023110.3(FGFR1):c.*1616T>G SNV Uncertain Significance
362865 rs886062908 GRCh37: 8:38269530-38269530
GRCh38: 8:38412012-38412012
38 FGFR1 NM_023110.3(FGFR1):c.*391C>T SNV Uncertain Significance
908881 rs764328455 GRCh37: 8:38270755-38270755
GRCh38: 8:38413237-38413237
39 FGFR1 NM_023110.3(FGFR1):c.*345T>A SNV Uncertain Significance
908882 rs751699851 GRCh37: 8:38270801-38270801
GRCh38: 8:38413283-38413283
40 FGFR1 NM_023110.3(FGFR1):c.*203G>A SNV Uncertain Significance
908949 rs750732571 GRCh37: 8:38270943-38270943
GRCh38: 8:38413425-38413425
41 FGFR1 NM_023110.3(FGFR1):c.-444C>T SNV Uncertain Significance
909210 rs1835972353 GRCh37: 8:38325854-38325854
GRCh38: 8:38468336-38468336
42 FGFR1 NM_023110.3(FGFR1):c.-466C>T SNV Uncertain Significance
909211 rs1835975713 GRCh37: 8:38325876-38325876
GRCh38: 8:38468358-38468358
43 FGFR1 NM_023110.3(FGFR1):c.-717C>T SNV Uncertain Significance
909277 rs772480875 GRCh37: 8:38326127-38326127
GRCh38: 8:38468609-38468609
44 FGFR1 NM_023110.3(FGFR1):c.-741A>G SNV Uncertain Significance
909278 rs971464879 GRCh37: 8:38326151-38326151
GRCh38: 8:38468633-38468633
45 SPECC1L-ADORA2A, SPECC1L NM_015330.6(SPECC1L):c.1915C>T (p.Arg639Ter) SNV Uncertain Significance
691567 rs1601553546 GRCh37: 22:24718863-24718863
GRCh38: 22:24322895-24322895
46 IGF1R NM_000875.5(IGF1R):c.580_581del (p.Lys194fs) DEL Uncertain Significance
691568 rs1596214904 GRCh37: 15:99251276-99251277
GRCh38: 15:98708047-98708048
47 CYP26B1 NM_019885.4(CYP26B1):c.1179G>T (p.Met393Ile) SNV Uncertain Significance
691569 rs1341772264 GRCh37: 2:72359716-72359716
GRCh38: 2:72132587-72132587
48 SPECC1L-ADORA2A, SPECC1L NM_015330.6(SPECC1L):c.1619G>A (p.Arg540His) SNV Uncertain Significance
691915 rs140698674 GRCh37: 22:24718567-24718567
GRCh38: 22:24322599-24322599
49 ERF NM_006494.4(ERF):c.383T>G (p.Val128Gly) SNV Uncertain Significance
691916 rs781452659 GRCh37: 19:42753881-42753881
GRCh38: 19:42249729-42249729
50 ERF NM_006494.4(ERF):c.1300G>A (p.Glu434Lys) SNV Uncertain Significance
691920 rs749808726 GRCh37: 19:42752964-42752964
GRCh38: 19:42248812-42248812

Copy number variations for Craniosynostosis from CNVD:

# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 97908 16 14700000 16700000 Duplication or deletion Craniosynostosis
2 112785 17 41062469 41719833 Deletion Craniosynostosis
3 142095 2 219500000 222200000 Duplication IHH Craniosynostosis

Expression for Craniosynostosis

Search GEO for disease gene expression data for Craniosynostosis.

Pathways for Craniosynostosis

Pathways directly related to Craniosynostosis:

# Pathway Source
1 Defective CYP26B1 causes RHFCA Reactome 66

GO Terms for Craniosynostosis

Cellular components related to Craniosynostosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.21 ZNF462 TWIST1 TRPS1 TFAP2B TCF20 TCF12
2 GLI-SUFU complex GO:1990788 8.8 GLI3 GLI2

Biological processes related to Craniosynostosis according to GeneCards Suite gene sharing:

(show all 35)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 10.51 FGFR2 GLI2 GLI3 MSX2 SOX11 TFAP2B
2 positive regulation of transcription by RNA polymerase II GO:0045944 10.4 FGFR2 GLI2 GLI3 KAT6A SOX11 TCF12
3 positive regulation of cell population proliferation GO:0008284 10.39 FGFR1 FGFR2 FGFR3 GLI2 SOX11 TFAP2B
4 negative regulation of apoptotic process GO:0043066 10.38 TWIST1 TFAP2B SMAD6 MSX2 GLI3 GLI2
5 kidney development GO:0001822 10.17 TFAP2B SOX11 GLI3 GLI2
6 osteoblast differentiation GO:0001649 10.16 TWIST1 MSX2 GLI3 GLI2
7 fibroblast growth factor receptor signaling pathway GO:0008543 10.14 FGFR3 FGFR2 FGFR1
8 skeletal system development GO:0001501 10.13 TRPS1 SOX11 GLI2 FGFR3 FGFR1
9 bone development GO:0060348 10.06 TWIST1 NPR2 FGFR2
10 chondrocyte differentiation GO:0002062 10.05 GLI3 GLI2 FGFR3
11 regulation of cell differentiation GO:0045595 10.04 TFAP2B GLI3 FGFR1
12 positive regulation of neuron differentiation GO:0045666 10.02 FGFR1 GLI2 SOX11 TCF12
13 odontogenesis GO:0042476 10 TWIST1 MSX2 FGFR2
14 outflow tract septum morphogenesis GO:0003148 10 SMAD6 MSX2 FGFR2
15 bone morphogenesis GO:0060349 9.96 MSX2 FGFR3 FGFR2
16 mitral valve morphogenesis GO:0003183 9.95 TWIST1 SMAD6
17 cranial suture morphogenesis GO:0060363 9.93 MSX2 TWIST1
18 negative regulation of smoothened signaling pathway GO:0045879 9.93 MEGF8 GLI3 GLI2
19 embryonic digestive tract morphogenesis GO:0048557 9.93 SOX11 GLI3 FGFR2
20 hindgut morphogenesis GO:0007442 9.88 GLI3 GLI2
21 frontal suture morphogenesis GO:0060364 9.87 GLI3 MSX2
22 smoothened signaling pathway involved in ventral spinal cord interneuron specification GO:0021775 9.85 GLI3 GLI2
23 embryonic digit morphogenesis GO:0042733 9.85 TWIST1 MSX2 GLI3 GLI2
24 hindlimb morphogenesis GO:0035137 9.83 TWIST1 TFAP2B
25 smoothened signaling pathway involved in dorsal/ventral neural tube patterning GO:0060831 9.8 GLI3 GLI2
26 embryonic skeletal system morphogenesis GO:0048704 9.8 GLI3 MEGF8 SOX11 TWIST1
27 negative regulation of hh target transcription factor activity GO:1990787 9.78 GLI3 GLI2
28 regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning GO:1901620 9.77 GLI3 GLI2
29 spinal cord dorsal/ventral patterning GO:0021513 9.76 GLI3 GLI2
30 tube development GO:0035295 9.69 GLI3 GLI2
31 smoothened signaling pathway involved in spinal cord motor neuron cell fate specification GO:0021776 9.67 GLI3 GLI2
32 embryonic limb morphogenesis GO:0030326 9.65 TWIST1 MSX2 MEGF8 GLI3
33 endochondral bone growth GO:0003416 9.63 MSX2 FGFR3 FGFR2
34 positive regulation of phospholipase activity GO:0010518 9.43 FGFR3 FGFR2 FGFR1
35 cellular response to endogenous stimulus GO:0071495 8.8 FGFR3 FGFR2 FGFR1

Molecular functions related to Craniosynostosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity GO:0003700 10.07 GLI2 GLI3 SOX11 TCF12 TFAP2B TRPS1
2 RNA polymerase II transcription regulatory region sequence-specific DNA binding GO:0000977 10.06 TWIST1 TRPS1 TFAP2B MSX2 GLI3 GLI2
3 transcription cis-regulatory region binding GO:0000976 10.02 TCF12 SOX11 SMAD6 MSX2 GLI2
4 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.88 FGFR3 FGFR2 FGFR1
5 DNA binding GO:0003677 9.86 ZNF462 TWIST1 TRPS1 TFAP2B TCF20 TCF12
6 cis-regulatory region sequence-specific DNA binding GO:0000987 9.83 TFAP2B TCF12 SOX11
7 fibroblast growth factor binding GO:0017134 9.63 FGFR3 FGFR2 FGFR1
8 fibroblast growth factor receptor activity GO:0005007 9.1 FGFR3 FGFR2 FGFR1

Sources for Craniosynostosis

8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
27 GO
28 GTR
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
36 LifeMap
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
70 Tocris
72 UMLS via Orphanet
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