Phenotypic Characteristics and Mutational Landscape of EYA1-related OTFCS and BORS: A Report of Two Families and Comprehensive Review

Abstract

This retrospective study explores the phenotypic and mutational spectrum of rare EYA1 -related diseases in two unrelated Indian families using whole exome sequencing and segregation analysis. Patient 1, a 3-year-old male with Otofaciocervical Syndrome 1 (OTFCS1) manifested facial dysmorphism, skeletal anomalies and joint contractures and carried a novel heterozygous frameshift variant (c.419del; p.Gly140ValfsTer101) in EYA1 causing protein truncation. Patient 2 described a 27-year-old mother whose deceased neonate exhibited features of BORS, with a heterozygous frameshift variant (c. 686delAinsTT; p.Tyr229PhefsTer3) in EYA1 . The father, who carried the same variant, had auditory and renal anomalies, highlighting variable expressivity. The study findings ultimately underscore the importance of broad genetic testing for the accurate diagnosis, counseling, and management of rare genetic diseases and the need for additional investigation to elucidate the mechanisms responsible for the variable penetrance and expressivity observed in EYA1 -related syndromes.