Kisho

Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy

craniosynostosis 2 (CRS2) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

craniosynostosis 2

MONDO:0011481

Also known as:CRS2MSX2-related craniosynostosisWarman-Mulliken-Hayward syndrome

Overview

A form of syndromic craniosynostosis, characterized by a highly variable craniosynostosis with frontal bossing, turribrachycephaly and cloverleaf skull anomaly. Hypoplasia of the supraorbital ridges, cleft palate, extra teeth and limb anomalies (triphalangeal thumb, 3-4 syndactyly of the hands, a short first metatarsal, middle phalangeal agenesis in the feet) have also been described. Associated problems include headache, poor vision, and seizures. Intelligence is normal.

GeneticsAutosomal dominant · MSX2 (chr 5)

ResearchLimited published research (4 articles)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include always present findings: Craniosynostosis; and sometimes findings: Triphalangeal thumb, Brachydactyly, Hypermetropia, and Trigonocephaly and others. 20 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	3	Seizure, Headache, Intellectual disability

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

MSX2 encodes msh homeobox 2 (267 aa). Acts as a transcriptional regulator in bone development. Represses the ALPL promoter activity and antagonizes the stimulatory effect of DLX5 on ALPL expression during osteoblast differentiation. Highest expression in Bladder (17.6 TPM) and Artery Tibial (11.3 TPM).

Craniosynostosis 2 is caused by mutations in the MSX2 gene on chromosome 5.

The MSX2 protein participates in RUNX2 gene expression from distal (P1) promoter is inhibited by NKX3-2, MSX2 and RUNX2-P1, and stimulated by DLX5,(DLX6), KLF4 stimulates CDH1 gene transcription, and Expression of MSX1 in the neural plate border pathways.

MSX2 is classified as a druggable target (Transcription Factor Complex category) with score 0.0.

Diagnosis

Genetic testing for MSX2 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for craniosynostosis 2 has been reported in the published literature.

Prognosis

Phenotype severity distribution: 1 always present feature.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for craniosynostosis 2.

4 publications have been identified in PubMed for craniosynostosis 2. Research spans Other (25%), Diagnostic / Biomarker (25%), and Case Report / Case Series (25%).

Recent Publications

Alter NE (2026). [PMID: 41483067](https://pubmed.ncbi.nlm.nih.gov/41483067/). *Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery*. [Diagnostic / Biomarker]
McGivern B (2025). [PMID: 39600096](https://pubmed.ncbi.nlm.nih.gov/39600096/). *HGG advances*. [Other]
Bambakidis E (2025). [PMID: 40146214](https://pubmed.ncbi.nlm.nih.gov/40146214/). *The Journal of craniofacial surgery*. [Case Report / Case Series]
Scagnet M (2025). [PMID: 38953669](https://pubmed.ncbi.nlm.nih.gov/38953669/). *Operative neurosurgery (Hagerstown, Md.)*. [Clinical Trial Publication]

Data assembled from 7 of 12 sources · Last updated Sep 19, 2026, 12:59 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:604757

Orphanet

European rare disease database

Orphanet:1541

GARD

Genetic and Rare Diseases Info Center

GARD:5538

Questions for Your Care Team

→Should I pursue genetic testing for MSX2, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

craniosynostosis 2

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Explore clinical features