## 3 Results
### Outcome
#### 3.3.1 Fissured Tongue  
Fissured tongue (FT) is a benign, usually asymptomatic condition characterized by deep grooves on the dorsal surface and margins of the tongue [22]. Eight works investigated the prevalence of FT in groups of children with DS (Table 4): one case report [12], six cohort studies [3; 9; 14; 17; 18; 20], and one age- and sex-matched case/control study [10]. The grouping by age of the subjects was heterogeneous among studies and details for each work have been summarized in Table 4, in the legend. \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline \multirow{3}{*}{**Observational Studies**} & \multirow{3}{*}{\begin{tabular}{c} **Bias Due to** \\ **Confounding** \\ \end{tabular} } & \multirow{3}{*}{\begin{tabular}{c} **Bias in** \\ **Participant** \\ **Selection** \\ \end{tabular} } & \multirow{3}{*}{\begin{tabular}{c} **Bias in** \\ **Classification of** \\ **Interventions** \\ \end{tabular} } & \multicolumn{3}{c}{**Bias Due to**} & \multicolumn{3}{c}{**Bias in**} & \multirow{3}{*}{\begin{tabular}{c} **Bias in** \\ **Missing** \\ **Data** \\ \end{tabular} } & \multirow{3}{*}{\begin{tabular}{c} **Bias in** \\ **Measurement** \\ **of Outcomes** \\ \end{tabular} } & \multirow{3}{*}{\
\begin{tabular}{c} **Bias in** \\ **Selection of** \\ **Bias** \\ **Result** \\ \end{tabular} } & \multirow{3}{*}{
\begin{tabular}{c} **Overall** \\ **Bias** \\ **Result** \\ \end{tabular} } \\ \[PERSON] et al. [9] & UR & LR & MR & MR & LR & LR & LR & MR \\ [PERSON] et al. [11] & UR & LR & LR & MR & LR & LR & LR & MR \\ [PERSON] et al. [12] & UR & MR & MR & MR & LR & LR & SR & MR \\ [PERSON] et al. [13] & UR & UR & LR & MR & MR & LR & LR & MR \\ [PERSON] et al. [15] & UR & UR & LR & MR & LR & LR & LR & MR \\ [PERSON] et al. [4] & UR & UR & MR & MR & LR & LR & LR & MR \\ [PERSON] et al. [10] & UR & UR & MR & MR & LR & LR & LR & MR \\ [PERSON] et al. [17] & UR & LR & MR & MR & LR & LR & LR & MR \\ [PERSON] et al. [19] & UR & SR & LR & MR & LR & LR & LR & SR \\ [PERSON] et al. [14] & UR & UR & MR & MR & MR & LR & LR & MR \\ [PERSON] et al. [18] & UR & SR & LR & MR & MR & LR & LR & SR \\ [PERSON] et al. [20] & UR & LR & LR & MR & MR & LR & LR & MR \\ [PERSON] & UR & LR & MR & MR & LR & LR & MR \\ et al. [21] & UR & SR & SR & MR & MR & MR & LR & SR \\ [PERSON] et al. [16] & UR & LR & MR & MR & LR & LR & LR & MR \\ \hline \hline \end{tabular}  
* The Risk of Bias in non-randomized studies—of interventions (ROBINS-I) tool was used for observational studies. Each domain was classified as low risk (LR), moderate risk (MR), serious risk (SR), and critical risk (CR), or not interpretable (UR). An overall bias assessment was then made using the same scale.  
\end{table} 
Table 3: Risk of bias assessment for individual studies. \begin{table}
\begin{tabular}{c|c|c|c|c|c|c|c|c} \hline \multicolumn{3}{c}{**Mean Age**} & \multicolumn{1}{c}{**Fissured Tongue**} \\ \hline \multicolumn{3}{c}{**(Range) Yr**} & \multicolumn{1}{c}{**0-1 Years**} & \multicolumn{1}{c}{**1-2 Years**} & \multicolumn{1}{c}{**2-5 Years**} & \multicolumn{1}{c}{**5-10 Years**} & \multicolumn{1}{c}{**10-15 Years**} & \multicolumn{1}{c}{**>15 Years**} & \multicolumn{1}{c}{**Total**} \\ \hline
**[PERSON] et al. ** [9] & 2.83 (0.17-25) & 1/28 (6\%) & 0/16 (0\%) & 5/15 (33\%) & & 9/12 (75\%) & & 15  
The prevalence of FT increased with age. In DS children aged 0-5 years, [PERSON] et al. [9] reported 10% in a total of 59 subjects, while [PERSON] et al. [3] found no FT in the 8 DS children considered in their study. In children with DS aged 5-10 years, [PERSON] et al. [3] found FT in 21% of 33 subjects and [PERSON] et al. [20] reported a prevalence of 78% of 9 subjects. In DS subjects between 10 and 15 years of age, FT varied from 34% of 50 subjects analyzed by [PERSON] et al. [3] to 67% in 21 children by [PERSON] et al. [20], up to 75% on 12 children reported by [PERSON] et al. [9]. [PERSON] et al. [12] reported a case of a 12-old girl with FT. Regarding DS subjects over the age of 15, only the data from [PERSON] et al. [3] and [PERSON] et al.