Anatomical variations and abnormalities of the maxillary region and clinical implications: A systematic review and metaanalysis.

OBJECTIVE: The objective of this review is to investigate and analyze the anatomical variations present in the maxillary sinus (MS), through the examination of the prevalence of these variations, as well as the corresponding prevalence of clinically significant pathologies and complications associated with them. METHODS: The search process was carried out in the following databases; MEDLINE, SCIELO, WOS, CINHAL, SCOPUS, and GOOGLE SCHOLAR, using as search terms; "Maxillary bone," "Maxillary sinus," "Paranasal sinus," "Anatomical variations," "Sinusitis" and "Clinical anatomy." RESULTS: A total of 26 articles and 12969 samples were included, from which 12,594 subjects had their sex recorded giving a total of 5802 males and 6792 females. The variants reported by the included were Haller cells, Concha Bullosa, Number of septa, Hypoplastic sinus, Agger Nasi, Thickening of the MS mucosa, Deviation of the nasal septum, Accessory ostium, and Onodi cells. Among the mentioned, the ones that presented the greatest number of studies (between 8 and 10 studies included) were: the Haller Cells, the Concha Bullosa, and the Number of septa, where prevalence was 0.30, 0.36, 0.39 respectively. These variations can lead to sinusitis, cause some types of tumors, or affect neighboring structures that could be compromised by this variation. CONCLUSION: As a result, it is certainly complex to distinguish the presence of anatomical variations from pathological abnormalities. Therefore, knowledge of the different variations and their clinical relationships could be a useful asset for clinicians dedicated to this region.

Beyond the exome: What's next in diagnostic testing for Mendelian conditions.

Despite advances in clinical genetic testing, including the introduction of exome sequencing (ES), more than 50% of individuals with a suspected Mendelian condition lack a precise molecular diagnosis. Clinical evaluation is increasingly undertaken by specialists outside of clinical genetics, often occurring in a tiered fashion and typically ending after ES. The current diagnostic rate reflects multiple factors, including technical limitations, incomplete understanding of variant pathogenicity, missing genotype-phenotype associations, complex gene-environment interactions, and reporting differences between clinical labs. Maintaining a clear understanding of the rapidly evolving landscape of diagnostic tests beyond ES, and their limitations, presents a challenge for non-genetics professionals. Newer tests, such as short-read genome or RNA sequencing, can be challenging to order, and emerging technologies, such as optical genome mapping and long-read DNA sequencing, are not available clinically. Furthermore, there is no clear guidance on the next best steps after inconclusive evaluation. Here, we review why a clinical genetic evaluation may be negative, discuss questions to be asked in this setting, and provide a framework for further investigation, including the advantages and disadvantages of new approaches that are nascent in the clinical sphere. We present a guide for the next best steps after inconclusive molecular testing based upon phenotype and prior evaluation, including when to consider referral to research consortia focused on elucidating the underlying cause of rare unsolved genetic disorders.