In this study, we describe three unrelated Japanese patients with hearing loss and symphalangism who were diagnosed with proximal symphalangism (SYM1), atypical multiple synostosis syndrome (atypical SYNS1) and stapes ankylosis with broad thumb and toes (SABTT), respectively, based on the clinical features. Surgical findings in the middle ear were similar among the patients. By next-generation and Sanger sequencing analyses, we identified two novel mutations, c.559C>G (p.P178A) and c.682T>A (p.C228S), in the SYM1 and atypical SYNS1 families, respectively. No pathogenic changes were found in the protein-coding regions, exon-intron boundaries or promoter regions of the NOG, GDF5 or FGF9 genes in the SABTT family. Such negative molecular data suggest there may be further genetic heterogeneity underlying SYNS1, with the involvement of at least one additional gene. Stapedotomy resulted in good hearing in all patients over the long term, indicating no correlation between genotype and surgical outcome. Given the overlap of the clinical features of these syndromes in our patients and the molecular findings, the diagnostic term 'NOG-related-symphalangism spectrum disorder (NOG-SSD)' is advocated and an unidentified gene may be responsible for this disorder.

Background: Ultra-high-resolution computed tomography (U-HRCT) utilizes a 1024 Â 1024 matrix with 0.25-mm section thickness, offering better spatial resolution than conventional multi-detector row CT to detect anatomic data for otologic surgery. Aims: We examined stapes footplate thickness using U-HRCT in relation to stapedotomy to predict the difficulty of the surgical procedure. Materials and methods: Subjects were 12 otosclerosis patients and 25 controls who underwent diagnostic U-HRCT. A profile curve (Hounsfield units) was used to measure stapes footplate thickness along a perpendicular line across the stapes footplate in a plane parallel to the lateral semicircular canal. Results: Footplate thickness was smaller at the midpoint than just before the anterior crus and just after the posterior crus. Interobserver variability was lowest at the midpoint, where foot plate thickness was significantly greater in the affected ear in otosclerosis patients compared with controls (0.60 ± 0.09 mm vs 0.46 ± 0.04 mm; p < .001). Otosclerosis patients were detected using U-HRCT with a high area under the curve. Difficulty in the stapes opening procedure correlated with stapes footplate thickness. Conclusions: Footplate thickness on U-HRCT correlated with temporal bone anatomy and corresponded to surgical difficulty. Significance: U-HRCT-derived anatomic data is useful for evaluating the stapes.