목적: Unilateral sensorineural hearing loss (USNHL) or single side deafness (SSD) cause educational and behavioral problems. The etiology of a substantial portion of USNHL/SSD cases remains unknown and genetic causes have not been clearly elucidated. USNHL/SSD was anecdotally reported in Waardenburg syndrome (WS) subjects. In this study, the authors tried to evaluate the heritability of USNHL/SSD. 방법:The authors recruited 50 unrelated children manifesting SSD and investigated whether there were either siblings or parents with hearing loss to address the heritability of SSD. They also took temporal bone CT or internal auditory canal MRI. For the molecular genetic diagnosis, the authors performed mutational analyses including Sanger sequencing of MITF, SOX10, and PAX3, and if necessary, targeted exome sequencing of 134 deafness genes. 결과:Among the 50 probands, the authors were able to identify four (8%) unrelated SSD children from four families (SH136, SB173, SB177 and SB199) with at least one more hearing impaired family member. Interestingly, the heritable SSD was statistically associated with presence of brown freckles or premature gray hair within the first degree relative of the probands which are the signs of WS. Subsequent molecular genetic tests have revealed that SB199 carried a substitution mutation of PAX3 (p.Arg223Gln) commonly found in WS type1. And SH136 carried a novel nonsense mutation of MITF (p.Arg356X), confirming a diagnosis of WS type2. 결론:The authors for the first time identify the heritability at least in 8% of UNSHL/SSD cases and report strong association of the heritability of UNSHL/SSD with WS. It seems crucial to obtain a comprehensive family history and perform a multidisciplinary physical examination not to miss gray hair, brown freckles especially in WS type2 if a child with congenital SSD visits the clinic. WS should be included in the differential diagnosis of children with UNSHL/SSD.