MKRN3 mutations represent the most common genetic cause of central precocious puberty (CPP) but associations between genotype and clinical features have not been extensively explored. This systematic review and meta-analysis investigated genotype-phenotype associations and prevalence of MKRN3 mutations in CPP. The search was conducted in seven electronic databases (Cochrane, EMBASE, LILACS, LIVIVO, PubMed, Scopus, and Web of Science) for articles published until 4 September 2018. Studies evaluating MKRN3 mutations in patients with CPP were considered eligible. A total of 22 studies, studying 880 subjects with CPP, fulfilled the inclusion criteria. Eighty-nine subjects (76 girls) were identified as harboring MKRN3 mutations. Girls, compared with boys, exhibited earlier age at pubertal onset (median, 6.0 years; range, 3.0 to 7.0 vs 8.5 years; range, 5.9 to 9.0; P < 0.001), and higher basal FSH levels (median, 4.3 IU/L; range, 0.7 to 13.94 IU/L vs 2.45 IU/L; range, 0.8 to 13.70 IU/L; P = 0.003), and bone age advancement ( Δ BA; median, 2.3 years; range, −0.9 to 5.2 vs 1.2 years; range, 0.0 to 2.3; P = 0.01). Additional dysmorphisms were uncommon. A total of 14 studies evaluating 857 patients were included for quantitative analysis, with a pooled overall mutation prevalence of 9.0% (95% CI, 0.04 to 0.15). Subgroup analysis showed that prevalence estimates were higher in males, familial cases, and in non-Asian countries. In conclusion, MKRN3 mutations are associated with nonsyndromic CPP and manifest in a sex-dimorphic manner, with girls being affected earlier. They represent a common cause of CPP in western countries, especially in boys and familial cases.

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Background/Aim Several strategies have been developed for tooth fragment reattachment following fracture. Although many techniques have been reported, there is no consensus on which one has the best results in terms of the bond strength between the fragment and the dentin over time. The aim of this study was to assess the currently reported tooth fragment reattachment techniques for fractured crowns of anterior teeth. Materials and Methods The PubMed, LILACS, Web of Science, Cochrane, and Scopus databases were searched in October 2016, and the search was updated in February 2017. A search of the gray literature was performed in Google Scholar and OpenGrey. Reference lists of eligible studies were cross‐checked to identify additional studies; gray literature and ongoing trials were investigated. Two authors assessed studies to determine inclusion and undertook data extraction. Case reports/series of three or more cases, cross‐sectional studies, cohort studies, and in vivo clinical trials in all languages were included. Results Five articles remained after screening. These studies predominantly reported on fragment reattachment with composite resin and resin cement. There was little consistency among the studies in regard to the technique used for tooth fragment reattachment and length of the follow‐up period. Conclusions According to the evidence found in the studies included in this review, simple tooth fragment reattachment was the preferred reattachment technique. An increase in the bond strength between tooth fragment and dentin was observed when an intermediate material was used. Further investigation is needed, using standard follow‐up periods and larger samples.

Fragment reattachment using a technique with no preparation and an adhesive system associated with an intermediate composite with good mechanical properties can restore part of the resistance of the fractured tooth.

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