Systematic Review of Nonsyndromic Craniosynostosis: Genomic Alterations and Impacted Signaling Pathways.

BACKGROUND: Genetic research in nonsyndromic craniosynostosis remains limited compared with syndromic craniosynostosis. This systematic review aimed to comprehensively summarize the genetic literature of nonsyndromic craniosynostosis and highlight key signaling pathways. METHODS: The authors performed a systematic literature search of PubMed, Ovid, and Google Scholar databases from inception until December of 2021 using search terms related to nonsyndromic craniosynostosis and genetics. Two reviewers screened titles and abstract for relevance, and three reviewers independently extracted study characteristics and genetic data. Gene networks were constructed using Search Tool for Retrieval of Interacting Genes/Proteins (version 11) analysis. RESULTS: Thirty-three articles published between 2001 and 2020 met inclusion criteria. Studies were further classified into candidate gene screening and variant identification studies ( n = 16), genetic expression studies ( n = 13), and common and rare variant association studies ( n = 4). Most studies were good quality. Using our curated list of 116 genes extracted from the studies, two main networks were constructed. CONCLUSIONS: This systematic review concerns the genetics of nonsyndromic craniosynostosis, with network construction revealing TGF-ß/BMP, Wnt, and NF-κB/RANKL as important signaling pathways. Future studies should focus on rare rather than common variants to examine the missing heritability in this defect and, going forward, adopt a standard definition.

Olfaction in pregnancy: systematic review and meta-analysis.

Little attention has been paid to olfactory changes during pregnancy with contemporary studies limited in number and sample size. We examined whether pregnancy is associated with differences in olfactory performance and if there were any specific gestational ages at which these differences occur through a comprehensive systematic review and meta-analysis of the current literature. An initial electronic database search identified 234 citations, which were screened at the abstract level. Twenty-three citations were germane for full-text review, and 13 met criteria for inclusion. Our review assessed 5 olfactory measures of interest: odor identification (n = 11 articles), threshold (n = 8), discrimination (n = 5), hedonics (n = 6), and intensity (n = 5). Nine of these 13 studies contained sufficient data for meta-analysis, and these studies included a total of 523 pregnant women and 365 non-pregnant controls. Despite previous subjective and objective reports of odor intolerances and odor hypersensitivity, we did not find any significant differences between pregnant and non-pregnant women in odor discrimination, thresholds, or hedonics. However, meta-analysis of 506 cases and 333 controls showed worse odor identification in pregnant women compared to controls in a random-effects model. Thus, we demonstrate worse performance at odor identification during pregnancy. In this review, we discuss the current evidence (and lack thereof) regarding olfaction in pregnancy as well as highlight current knowledge gaps in this field.