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BackgroundWith the advancement of next-generation sequencing, clinicians are now able to detect ultra-rare mutations that are barely encountered by the majority of physicians. Ultra-rare and rare diseases cumulatively acquire a prevalence equivalent to type 2 diabetes with 80% being genetic in origin and more prevalent among high consanguinity communities including Saudi Arabia. The challenge of these diseases is the ability to predict their prevalence and define clear phenotypic features.MethodsThis is a non-interventional retrospective multicenter study. We included pediatric patients with a pathogenic variant designated as ultra-rare according to the National Institute for Clinical Excellence's criteria. Demographic, clinical, laboratory, and radiological data of all patients were collected and analyzed using multinomial regression models.ResultsWe included 30 patients. Their mean age of diagnosis was 16.77 months (range 3-96 months) and their current age was 8.83 years (range = 2-15 years). Eleven patients were females and 19 were males. The majority were of Arab ethnicity (96.77%). Twelve patients were West-Saudis and 8 patients were South-Saudis. SCN1A mutation was reported among 19 patients. Other mutations included SZT2, ROGDI, PRF1, ATP1A3, and SHANK3. The heterozygous mutation was reported among 67.86%. Twenty-nine patients experienced seizures with GTC being the most frequently reported semiology. The mean response to ASMs was 45.50% (range 0-100%).ConclusionThe results suggest that ultra-rare diseases must be viewed as a distinct category from rare diseases with potential demographic and clinical hallmarks. Additional objective and descriptive criteria to detect such cases are needed.

Background:. Although many published studies have investigated the benefits of tranexamic acid (TXA) in reducing perioperative bleeding, no large meta-analysis has been conducted to demonstrate its overall benefit. Methods:. A systematic review was performed by following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Cochrane, Ovid, Embase, Web of Science, ClinicalTraisl.Gov, and Scopus databases were searched for articles reporting the benefit of TXA in reducing perioperative bleeding in craniosynostosis surgery from establishment through October 2022. The results of our meta-analysis were pooled across the studies using a random-effects model, and presented as a weighted mean difference with 95% confidence interval (95% CI). Results:. The database search yielded 3207 articles, of which 27 studies with a corresponding number of 9696 operations were eligible. The meta-analysis included only 18 studies, accounting for 1564 operations. Of those operations, 882 patients received systemic TXA, whereas 682 patients received placebo (normal saline), no intervention, low dose TXA, or other control substances. This meta-analysis demonstrated a significant beneficial effect of TXA in reducing perioperative bleeding, particularly when compared with other controlled substances, with a weighted mean difference of −3.97 (95% CI = −5.29 to −2.28). Conclusions:. To our knowledge, this is the largest meta-analysis in the literature investigating the benefit of TXA in reducing perioperative blood loss in craniosynostosis surgery. We encourage implementing TXA-protocol systems in hospitals after the appraisal of the data presented in this study.