Sensorineural hearing impairment is a common sensory deficit in children and more than 50% of these cases are caused by genetic etiologies, that is, hereditary hearing impairment (HHI). Recent advances in genomic medicine have revolutionized the diagnostics of, and counseling for, HHI, including preimplantation genetic diagnosis (PGD), thus providing parents-to-be with better reproductive choices. Over the past decade, we have performed PGD using the amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) technique in 11 couples with a history of HHI, namely eight with GJB2 variants, one with OTOF variants, one with SLC26A4 variants, and one with an MITF variant. We demonstrated that PGD can be successfully applied to HHI of different inheritance modes, namely autosomal dominant or recessive, and phenotypes, namely syndromic or non-syndromic HHI. However, certain ethical concerns warrant scrutiny before PGD can be widely applied to at-risk couples with a history of HHI.

Rationale:Mitochondrial DNA mutations have been associated with many maternal inherited diseases. A1555G mutation in mtDNA effects the gene code for rRNA, resulting in the structural change of human ribosome rending it susceptible to binding of the common antibiotic, aminoglycosides. Such mutation has linked with non-syndromic hearing loss and is one of the most common mtDNA mutations in Asian populations.Patient concerns:A 50-year-old Taiwanese female visited our neurology department with concern for multiple members with hearing loss in her family, including herself.Diagnoses:Physical examination findings were not significant besides hearing loss and brain MRI did not reveal any lesions. BAEP confirmed bilateral peripheral sensory deficit. Given the multiple cases of hearing loss in the family, a genetic cause was suspected. Using PCR and sequences chromatogram technique we have identified A1555G mutation on her mtDNA affecting region codes for 12S rRNA. Additionally, we observed severe speech disorder in two young family members with the onset of hearing loss began in their early childhood.Interventions:The patient declined any form of intervention at the time for personal reasons.Outcomes:The patient was satisfied with the diagnosis, her and her families are continuously followed by our neurology department.Lessons:We report on a family with mtDNA mutation hearing loss that is related to exposure to aminoglycosides. Children with such mutation are at high risk for impaired linguistic function. Early identification and intervention with cochlear implant should be considered.