Jones Syndrome: a systematic literature review

Background: Jones syndrome is an extremely rare genetic condition characterized by the coexistence of gingival fibromatosis and progressive sensorineural hearing loss. It is an autosomal dominant disorder whose genetic basis has been identified, through exome sequencing technology, as pathogenic mutations in exon 5 of the Repressor Element 1 Silencing Transcription Factor (REST) gene. This review aimed to evaluate whether integrating genetic testing improves the diagnostic accuracy of Jones syndrome compared with clinical assessment alone. Methods: An electronic and manual search was conducted in August 2025 across multiple databases (PubMed, Cochrane Library, Google Scholar, Scopus, and Web of Science) in accordance with PRISMA guidelines. Two independent reviewers performed the search. From eligible studies, the following data were extracted: author and year of publication, study design, patient age and sex, oral manifestations, systemic manifestations, diagnostic and therapeutic approaches, severity of gingival fibromatosis, and degree of sensorineural hearing loss (SNHL). Any disagreements were resolved through discussion with a third reviewer and by consensus. Results: The electronic and manual search retrieved 9,864 records. After removal of duplicates (n = 15) and title screening, 9,837 articles were excluded, leaving 12 articles for abstract and full-text screening. Two articles were excluded because their full texts were unavailable. After full-text assessment, four additional articles were excluded, resulting in six studies included in the review. The included studies comprised four case reports without genetic analysis and two studies that included analysis of the Repressor Element 1 Silencing Transcription Factor (REST) gene, documenting familial cosegregation. Conclusions: REST gene analysis currently represents an essential diagnostic tool, as it complements the clinical workup, increases diagnostic accuracy, and opens new perspectives for the management and support of patients with Jones syndrome.