EYA1-related disorders: Two clinical cases and a literature review

Objectives To delineate the diagnostic and rehabilitative aspects of syndromes that have overlapping features, we present the cases of two unrelated Caucasian males affected by hearing impairment, preauricular pits and cervical fistulae. Specific findings that are helpful in the diagnosis and management of EYA1-related disorders are highlighted. Methods Genetic, otologic, imaging, eye and renal evaluations were conducted to achieve a detailed and comprehensive assessment, leading to the most accurate diagnosis and appropriate treatment. A literature review was also carried out. Results Diagnostic criteria indicated that the two patients were affected by BOS1 (Branchio-Otic Syndrome 1). We also identified a novel sporadic missense mutation in the EYA1 gene: p.G533R (c.1597G > A, NM_000503.4), a highly conserved, heterozygotic amino acid substitution. In the other case, we identified the p.X593QextX6 (c.1777T > A, NM_000503.4) substitution, known to be responsible for BO/BOR phenotypes. Both substitutions lead to isoform 1 (EYA1B and EYA1C) which is composed of 592 amino acids. Clinical and in silico evidence suggests a pathogenic role for the new, never before described p.G533R mutation. Imaging evaluation revealed a complex pathology, characterized by external, inner and middle ear malformations, without renal anomalies. Conclusions Our results demonstrate the importance of considering the imaging evaluation and the complete DNA sequencing of the EYA1 gene for the differential diagnosis of deafness and related branchio-oto-renal disorders.