## 4 Discussion  
Various syndromic genetic disorders can be associated with oral manifestations, and, while some of them are extremely rare [23; 24; 25; 26; 27], many others are commonly seen: this is the case with Down syndrome (DS). DS is well known and its phenotypic aspect has been extensively described, but there is no systematic report on the particular prevalence of oral mucosal manifestation in children with DS. Therefore, the present work systematically investigated the scientific literature to establish the conditions of the oral mucosa reported in children and young adults (from 0 to 25 years of age) with DS. Among the 150 papers found, only 14 fulfilled the inclusion criteria for the qualitative review. The most reported findings were fissured tongue and lip lesions/cheilitis. Fissured tongue is a relatively common condition, more frequent in adulthood than in childhood, with a prevalence of approximately 2-5% of the general population, and ranging between 10-95% in DS, regardless of age [28]. In the studies considered here, although a precise stratification of prevalence percentages by years of age was not always reported, due to the different grouping systems adopted by the various authors, it was observed that the average prevalence of fissured tongue increases with age, being on average reported in 35% of children between 0-15 years (very rare before 2 years of age) and 65% of subjects over 15 years of age. The highest prevalence of FT was found by [PERSON] et al. [17] in 52% of 67 children younger than 15 years. Geographic tongue (GT) is reported in 1-3% of the healthy population, with no difference between females and males and ages [22]. Our results reported higher percentages of GT in DS children, being, in all studies considered, higher than the average prevalence in the population without Down syndrome. However, discordant trends were observed by age groups, as GT was reported higher (14%) in 0-5 years of age compared to 6-25 years in one study [9] and the opposite by [PERSON] et al. [3] (4% of DS subjects between 6-20 years). Cheilitis was reported in eight studies, but the definitions of sites and origins were homogeneous and not always considered. In particular, in the works in which the examination was performed by dentists and/or oral pathologists; these data were generally more defined than those reported by dermatologists or other medical specialists. Oral candidiasis, _Candida_ spp. typing and carriages have been the subject of various studies considered. Active oral candidiasis at clinical examination was more common in children/young adults with DS than in controls, as was the carrier status with no clinical signs of infection. Only the work by [PERSON] et al. [19] has countered this finding, as they reported the frequency of the _Candida_ spp. carriage was higher in the control group than in the DS, without reaching statistical significance. This could explain the lower caries rates in children with DS compared to healthy controls, but it does not endorse their greater susceptibility to oral candidiasis, thus imputing greater responsibility towards immunological disorders and/or oral lesions co-occurring in DS than the simple load of _Candida_ spp. [29; 30; 31]. This hypothesis is reinforced by the evidence that _C. albicans_ was the most prevalent species in both healthy subjects and DS ones, as well as it was found twice as frequently in those DS patients with lip lesions compared to those without lip lesions [13; 20]; thus supporting the role of immunity, hyposlavation, and oral lesions in the onset of frequent oral infections in children with DS. Lastly, the work by [PERSON] et al. [16] highlighted the coexistence of other _Candida species_ (non-albicans Candida, NAC) besides _C. albicans_ in DS compared with controls. Only sporadic reports have been found regarding other oral mucosal conditions, such as herpes labialis, ulcerative/traumatic lesions, and check biting.