Clinical and Genetic Characterization of Craniosynostosis in Saudi Arabia
Open accessAbstract
Background: Craniosynostosis (CS) is defined as pre-mature fusion of one or more of the cranial sutures. CS is classified surgically as either simple or complex based on the number of cranial sutures involved. CS can also be classified genetically as isolated CS or syndromic CS if the patient has extracranial deformities. Currently, the link between clinical and genetic patterns of CS in the Saudi population is poorly understood. Methodology: We conducted a retrospective cohort study among 28 CS patients, of which 24 were operated and four were not. Clinical and genetic data were collected between February 2015 and February 2019, from consenting patient's families. The electronic chart data were collected and analyzed including patient demographics, craniofacial features, other anomalies and dysmorphic features, operative data, intra cranial pressure (ICP), parent consanguinity and genetic testing results. Results: The most common deformity in our population was trigonocephaly. The most performed procedure was cranial vault reconstruction with fronto-orbital advancement, followed by posterior vault distraction osteogenesis and suturectomy with barrel staving. Genetics analysis revealed pathogenic mutations in FGFR2 (6 cases), TWIST1 (3 cases), ALPL (2 cases), and TCF12 (2 cases), and FREM1 (2 case). Conclusion: Compared to Western countries, our Saudi cohort displays significant differences in the prevalence of CS features, such as the types of sutures and prevalence of inherited CS. The genomic background allows our phenotype-genotype study to reclassify variants of unknown significance. Worldwide, the sagittal suture is the most commonly affected suture in simple CS, but in the Saudi population, the metopic suture fusion was most commonly seen in our clinic. Further studies are needed to investigate the characteristics of CS in our population in a multicenter setting.
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Variants in genes such as FGFR2, TCF12, ERF, KAT6B, ACTB, SH3PXD2B, SALL1, IFT140, SON, CASK, FOXP2, EXTL3, and SOX6 have often been identified in patients with additional dysmorphic, skeletal, neurodevelopmental, or systemic disorders.
“More broadly, variants in genes such as FGFR2, TCF12, ERF, KAT6B, ACTB, SH3PXD2B, SALL1, IFT140, SON, CASK, FOXP2, EXTL3, and SOX6 have often been identified in patients with additional dysmorphic, skeletal, neurodevelopmental, or systemic disorders [41, 47–49, 78, 84, 86, 90, 100, 101, 108–110].”
From Genetics versus environment in the pathophysiology of sagittal synostosis (2026) · cites this paper as [41]
The Discussion (page not provided) links FGFR2, ERF, and TCF12 to syndromic craniosynostosis, and the Results: Molecular Analysis report FGFR2 variants in six patients with characteristic facial, hand, or foot findings. Our copy does not substantiate the claim for the other listed genes or establish how often variants across that full list occur in patients with the stated additional disorders. (LLM, conf=0.86)
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Genetics versus environment in the pathophysiology of sagittal synostosis
De Gregorio, V., Tosi, D. D., Vita, A., Salvati, M., Massimi, L., Tamburrini, G., Tiberio, F., & Lattanzi, W. (2026) · Child's Nervous System · doi:10.1007/s00381-026-07396-5 · Cited by 2 · see citing works
“…variants in genes such as FGFR2 , TCF12 , ERF , KAT6B , ACTB , SH3PXD2B , SALL1 , IFT140 , SON , CASK , FOXP2 , EXTL3 , and SOX6 have often been identified in patients with additional dysmorphic, skeletal, neurodevel-opmental, or systemic disorders [41, 47–49, 78, 84, 86, 90, 100, 101, 108–110].”
- Authors
- Alghamdi, M., Alhumsi, T. R., Altweijri, I., Alkhamis, W. H., Barasain, O., Cardona-Londoño, K. J., Ramakrishnan, R., Guzmán-Vega, F. J., Arold, S. T., Ali, G., Adly, N., Ali, H., Basudan, A., & Bakhrebah, M. A.
- Affiliations
- King Saud Medical City (SA)
- King Saud University (SA)
- King Abdullah University of Science and Technology (SA)
- Centre National de la Recherche Scientifique (FR)
- Imam Mohammad ibn Saud Islamic University (SA)
- King Abdulaziz City for Science and Technology (SA)
- Corresponding author
- Alghamdi, Malak
- Alhumsi, Taghreed R.
- ORCID
- Venue
- Frontiers in Pediatrics
- Publisher
- Frontiers Media SA
- Published
- 2021-04-16
- Volume
- 9
- Pages
- 582816-582816
- ISSN
- 2296-2360 (ISSN-L)
- PMC
- PMC8085561
- OpenAlex
- W3152711861
- Cited by
- 15
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 1
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pediatrics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- King Abdullah University of Science and Technology Repository (King Abdullah University of Science and Technology) (submittedVersion, other-oa)
- Funders
- King Saud University
- King Abdullah University of Science and Technology (FCC/1/1976‐25, REI/1/4446–01)
- King Abdulaziz City for Science and Technology (5-18-03-001-0010)
- National Plan for Science, Technology and Innovation
- Deanship of Scientific Research, King Saud University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Health Sciences › Medicine › Surgery › Pectus Deformity Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Keywords
- craniosynostosis, Saudi population, FGFR2 mutations, TWIST1, ALPL, TCF12, FREM1, trigonocephaly, cranial vault reconstruction, fronto-orbital advancement, consanguinity, genotype-phenotype correlation, syndromic craniosynostosis, variants of uncertain significance
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