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We report a Chinese pedigree characterized by proximal symphalangism, conductive hearing loss, and distinctive facies. We examined the genetic cause and reviewed the literature to discuss the pathogeny, treatment, and prevention of SYNS1. Audiological, ophthalmological, and radiological examinations were evaluated. Whole\u2010exome sequencing (WES) was performed to identify mutations in the proband and her parents. Sanger sequencing was used to verify the results for the proband, parents, and grandmother. The literature on the genotype\u2013phenotype correlation was reviewed. The patient was diagnosed with multiple synostoses syndrome clinically. WES and bioinformatic analysis revealed a novel missense mutation in the <jats:italic>NOG<\/jats:italic> gene, c.554C&gt;G (p.Ser185Cys), cosegregated in this family. The literature review showed that the phenotype varies widely, but the typical facies, conductive hearing loss, and proximal symphalangism occurred frequently. All reported mutations are highly conserved in mammals based on conservation analysis, and there are regional hot spots for these mutations. However, no distinct genotype\u2013phenotype correlations have been identified for mutations in <jats:italic>NOG<\/jats:italic> in different races. Regular systematic examinations and hearing aids are beneficial for this syndrome. However, the outcomes of otomicrosurgery are not encouraging owing to the regrowth of bone. This study expanded the mutation spectrum of <jats:italic>NOG<\/jats:italic> and is the first report of SYNS1 in a Chinese family. Genetic testing is recommended as part of the diagnosis of syndromic deafness. A clinical genetic evaluation is essential to guide prevention, such as preimplantation genetic diagnosis.<\/jats:p>","DOI":"10.1002\/ajmg.a.61583","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T16:08:10Z","timestamp":1586275690000},"page":"1438-1448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Multiple synostoses syndrome: Clinical report and retrospective analysis"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8366-5697","authenticated-orcid":false,"given":"Zhaoyu","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Institute of Otolaryngology, Genetic Testing Center for Deafness, Chinese PLA General Hospital  Beijing China"},{"name":"National Clinical Research Center for Otolaryngologic Diseases  Beijing China"},{"name":"Key Lab of Hearing Impairment Science of Ministry of 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