Apert syndrome is a rare congenital abnormality characterized by the fusion of multiple cranial sutures (craniosynostosis) and distinctive malformations of the skull, face, hands, feet, and dentition. Variations in the fibroblast growth factor receptor 2 (FGFR-2) gene are the cause of Apert syndrome. Currently, there is still a gap in knowledge about oro-dental features in patients with Apert syndrome. This study aimed to characterize Cranio-oro-facial manifestation and identify genetic variations related to Apert syndrome in Thai patients. Two Thai patients with Apert syndrome receiving treatment at the Princess Sirindhorn Craniofacial Center (PSC center) at King Chulalongkorn Memorial Hospital were recruited. Medical and dental records were obtained. Physical and oral manifestations, oral hygiene (OHI-S) and caries status (DMFT, dmft, DMFS, dmfs), occlusion, and maxillomandibular relationship were investigated. Pathogenic variants associated with Apert were identified by Sanger sequencing. Patient-1 and Patient-2 showed typical Apert features including craniosynostosis, hand syndactyly, and dysmorphic facial features. Cephalometric analysis revealed that the patients had retrognathic maxilla, proclined upper incisors, retroclined lower incisors, and protruded lower lip. Compared with general Thai children of the same sex and age, the patients had higher caries prevalence and caries risk score assessment. Sanger sequencing identified that both patients had hot-spot FGFR2 variants. Patient-1 possessed the heterozygous missense variant, c.755C>G (p.Ser252Trp) and Patient-2 harbored the heterozygous missense variant, c.758C>G (p.Pro253Arg). The identified pathogenic FGFR2 variants corresponding with patients’ phenotypes indicate that both patients were affected with Apert syndrome. The patients with Apert syndrome exhibit multiple Cranio-oro-facial anomalies. With poor oral hygiene and high caries risk, our study suggests that a multidisciplinary team is essential to deliver prompt management of Cranio-oro-facial abnormalities in patients with Apert syndrome. Vigilant dental check-ups and oral hygiene care must be implemented for the patients.