Genetic Characteristic of Thai Patients with Primary Craniosynostosis
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction:
Primary craniosynostosis comprises cranial anomalies caused by premature fusion of one or more sutures due to primary ossification defects, occurring in isolated or syndromic forms. Its prevalence is approximately 1 in 2500 live births, and it is characterized by substantial phenotypic and genetic heterogeneity. Advances in exome sequencing (ES) and genome sequencing (GS) have enabled more precise identification of disease-associated variants and novel causative genes. Our objective of this study is to evaluate the diagnostic yield of genetic testing methods, including Sanger sequencing, ES, and GS in patients with primary craniosynostosis.
Methods:
We recruited 91 primary craniosynostosis patients at King Chulalongkorn Memorial Hospital (January 2018 and September 2024), who were examined by clinical geneticists and craniofacial surgeons and underwent Sanger sequencing, ES or GS.
Results:
Among 91 patients, the overall diagnostic yield was 68.1% (62 patients). For 40 patients clinically diagnosed with Apert, Crouzon, or Pfeiffer syndromes, genetic testing identified pathogenic variants in 39 (97.5%), with Sanger sequencing of FGFR2 exons 7 and 8 achieving an 80.9% (17/21) yield. For 51 patients with other syndromic or isolated forms, ES and GS identified variants in 44.4% (16/36) and 46.7% (7/15), respectively, across 18 genes.
Conclusion:
Comprehensive genetic testing offers precise diagnoses for primary craniosynostosis, highlighting its clinical value in providing targeted patient care.
Primary craniosynostosis comprises cranial anomalies caused by premature fusion of one or more sutures due to primary ossification defects, occurring in isolated or syndromic forms. Its prevalence is approximately 1 in 2500 live births, and it is characterized by substantial phenotypic and genetic heterogeneity. Advances in exome sequencing (ES) and genome sequencing (GS) have enabled more precise identification of disease-associated variants and novel causative genes. Our objective of this study is to evaluate the diagnostic yield of genetic testing methods, including Sanger sequencing, ES, and GS in patients with primary craniosynostosis.
Methods:
We recruited 91 primary craniosynostosis patients at King Chulalongkorn Memorial Hospital (January 2018 and September 2024), who were examined by clinical geneticists and craniofacial surgeons and underwent Sanger sequencing, ES or GS.
Results:
Among 91 patients, the overall diagnostic yield was 68.1% (62 patients). For 40 patients clinically diagnosed with Apert, Crouzon, or Pfeiffer syndromes, genetic testing identified pathogenic variants in 39 (97.5%), with Sanger sequencing of FGFR2 exons 7 and 8 achieving an 80.9% (17/21) yield. For 51 patients with other syndromic or isolated forms, ES and GS identified variants in 44.4% (16/36) and 46.7% (7/15), respectively, across 18 genes.
Conclusion:
Comprehensive genetic testing offers precise diagnoses for primary craniosynostosis, highlighting its clinical value in providing targeted patient care.