Chrono-immunotherapy in genitourinary oncology: From emerging evidence to clinical translation (Review).

Down syndrome (DS), also known as trisomy 21, is the most common chromosomal disorder associated with intellectual disability. It results from the presence of an extra copy of chromosome 21 []. Individuals with DS typically present with a characteristic phenotype that includes developmental delay, hypotonia, distinctive craniofacial features, and a higher prevalence of congenital heart disease (CHD), endocrine disorders, hearing impairment, and other systemic conditions []. In Saudi Arabia, DS is notably prevalent, with an estimated incidence of one in 554 live births, a rate higher than that reported in many Western countries []. Advanced maternal age remains the principal risk factor, although demographic and cultural factors may also contribute to the increased prevalence observed in the Kingdom []. From a dental perspective, children with DS frequently exhibit oral, craniofacial, and airway abnormalities that significantly influence oral health and dental management [-]. Common findings include delayed tooth eruption, atypical tooth morphology, periodontal disease, malocclusion, hypodontia, relative macroglossia, and disturbances in craniofacial growth [-]. Medical comorbidities, such as CHD, obstructive sleep apnea (OSA), hypotonia, and possible cervical spine instability, may further complicate dental treatment planning, behavior management, and the safe delivery of sedation or general anesthesia [,]. Consequently, a thorough understanding of characteristic dental findings and associated medical conditions is essential for general dentists to provide safe, effective, and comprehensive oral healthcare for this population. Recent evidence emphasizes that periodontal disease is one of the most clinically important oral health concerns in individuals with DS. The increased susceptibility is thought to be multifactorial, involving immune dysregulation, altered oral microbiota, reduced manual dexterity, hypotonia, mouth breathing, and challenges in maintaining effective plaque control [,]. Although dental caries has traditionally been reported as less frequent in some children with DS, recent systematic reviews indicate that the evidence remains inconsistent and should not reduce the emphasis on caries prevention [,]. Therefore, preventive care should include early dental assessment, individualized oral hygiene instruction, caregiver education, dietary counseling, fluoride exposure, fissure sealants when indicated, and more frequent periodontal monitoring. Dental management of children with DS should be individualized and coordinated with the child’s medical team. Behavior guidance may require shorter appointments, desensitization visits, visual communication aids, positive reinforcement, and close caregiver involvement [,]. For children requiring sedation or general anesthesia, careful preoperative assessment is essential because airway obstruction, OSA, CHD, hypotonia, and possible cervical spine instability may increase perioperative risk [,]. Accordingly, dentists should document relevant medical history, obtain appropriate medical clearance when needed, and ensure that advanced procedures are performed in settings equipped for pediatric airway and medical emergencies.