Otofaciocervical Syndrome

Graziani et al. “Otofaciocervical Syndrome and Its Overlap with Branchiootorenal Spectrum: An Integrated Literature Analysis of EYA1-Related Disorders, Including a Novel Case with an 8q13.2q13.3 Deletion”. “Genes” 2025, v. 16, 1267

Craniofacial syndrome associated with branchial arch anomalies, or congenital neck defects, represent a diverse group of disorders that include Otofaciocervical syndrome (OTFCS) and branchiootorenal spectrum disorders (BORSD). OTFCS is characterized by craniofacial features (such as a long triangular face, broad forehead, narrow nose, and mandible, and high arched palate), ear anomalies, and shoulder anomalies. BORSD has traditionally been defined by a triad of branchial, otologic, and renal anomalies. Both conditions have shared clinical manifestations, but the facial features and shoulder anomalies were historically considered to be specific to OTFCS and the renal anomalies were considered specific to BORSD. Heterozygous variants in a gene called EYA1 have been observed in patients with OTFCS and BORSD. Graziani et al. report a novel patient with OTFCS who had an 8q13 microdeletion encompassing EYA1 and performed a comprehensive review of all EYA1-related disorders. The proband is a 22-year-old female who had severe congenital bilateral mixed hearing loss, bilateral preauricular fistulas, hypoplasia of the left shoulder muscles, winged scapula, short stature, and a history of speech delay. Chromosomal microarray identified a de novo 2.3 Mb interstitial microdeletion at 8q13.2q13.3 which involved 12 genes— LINC01592, LINC01603, SULF1, SLCO5A1, PRDM14, NCOA2, LOC101926892, TRAM1, LACTB2-AS1, LACTB2, XKR9, and EYA1. To the authors’ knowledge, the current case is the first report of OTFCS due to a microdeletion encompassing EYA1. The authors collected more than 200 records of EYA1-related disorders. Renal involvement was absent in 24% of EYA1 variant cases within the BORSD spectrum, whereas the majority of published patients with OTFCS presented with renal anomalies. This observation, the authors note undermines the previous clinical separation between the two conditions. The authors further argue to group both conditions under the larger umbrella of EYA1-related disorders due to the clinical overlap.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. Review and formatting by Nicole Talaba, MS CGC. For more information on any article please contact info@chromodisorder.org