FOXI3 pathogenic variants cause one form of craniofacial microsomia.

Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown. A total of 670 patients belonging to unrelated pedigrees with European and Chinese ancestry with CFM, are investigated. We identify 18 likely pathogenic variants in 21 probands (3.1%) in FOXI3. Biochemical experiments on transcriptional activity and subcellular localization of the likely pathogenic FOXI3 variants, and knock-in mouse studies strongly support the involvement of FOXI3 in CFM. Our findings indicate autosomal dominant inheritance with reduced penetrance, and/or autosomal recessive inheritance. The phenotypic expression of the FOXI3 variants is variable. The penetrance of the likely pathogenic variants in the seemingly dominant form is reduced, since a considerable number of such variants in affected individuals were inherited from non-affected parents. Here we provide suggestive evidence that common variation in the FOXI3 allele in trans with the pathogenic variant could modify the phenotypic severity and accounts for the incomplete penetrance.

Prospective evaluation of oral corticosteroid as a predictor of postoperative olfactory recovery after functional endoscopic surgery for nasal polyposis.

PURPOSE: Anticipating the possibility of olfactory recovery after functional endoscopic surgery (FES) in nasal polyposis (NP) is difficult. The main objective of this study was to assess the predictive factors of recovering the sense of smell after radical bilateral ethmoidectomy. Secondary objectives were to identify other predictors of olfactory recovery. METHODS: Open prospective study was conducted at the Nantes University Hospital including all patients with NP operated on in the Ear, Nose, and Throat Department between January 2011 and September 2017. These patients underwent functional endoscopic surgery (radical ethmoidectomy) after medical treatment failure. Olfaction was quantified prospectively and systematically during the preoperative consultation using a visual analog scale. Multivariate analysis evaluated the presence of predictive factors of postoperative olfactory recovery. RESULTS: One hundred nineteen patients were included in the study. Overall, olfaction was partially improved after surgery. For patients who presented greater than 50% recovery of olfaction after systemic corticosteroid therapy before surgery, we observed a predictive better rate of olfactory recovery after surgery (p < 0.001). Age over 65 years, a history of sinonasal surgery, associated asthma, and bacterial colonization were not associated with less postoperative olfactory recovery. CONCLUSION: This study identified an objective factor that may influence olfactory recovery after FES using a therapeutic trial for olfactory recovery after oral corticosteroid treatment taken before surgery.