Clinical and Genetic Characterization of Craniosynostosis in Saudi Arabia

Malak Alghamdi; Taghreed R Alhumsi; Ikhlass Altweijri; Waleed H Alkhamis; Omar Barasain; Kelly J Cardona-Londoño; Reshmi Ramakrishnan; Francisco J Guzmán-Vega; Stefan T Arold; Ghaida Ali; Nouran Adly; Hebatallah Ali; Ahmed Basudan; Muhammed A Bakhrebah

doi:10.3389/fped.2021.582816

Clinical and Genetic Characterization of Craniosynostosis in Saudi Arabia

Front Pediatr. 2021 Apr 16:9:582816. doi: 10.3389/fped.2021.582816. eCollection 2021.

Authors

Affiliations

¹ Medical Genetic Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
² Department of Pediatrics, King Saud University Medical City, Riyadh, Saudi Arabia.
³ Department of Plastic Surgery, King Saud University Medical City, Riyadh, Saudi Arabia.
⁴ Department of Neurosurgery, King Saud University Medical City, Riyadh, Saudi Arabia.
⁵ Obstetrics and Gynecology, King Saud University Medical City, Riyadh, Saudi Arabia.
⁶ College of Medicine, King Saud University, Riyadh, Saudi Arabia.
⁷ Biological and Environmental Science and Engineering (BESE), Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
⁸ Center de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, Montpellier, France.
⁹ College of Medicine, Imam Muhammad Ibn Saud University, Riyadh, Saudi Arabia.
¹⁰ College of Medicine Research Centre, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
¹¹ Chair of Medical and Molecular Genetics, Department of Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia.
¹² Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.

Abstract

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.

Keywords: ALPL gene; FGFR2 gene; TCF12 gene; TWIST1 gene; craniosynostosis; exome sequencing; trigonocephaly.