The Role of Clinical Observation: Red Flag 4 — Cardiomyopathies and Sensorineural Hearing Loss

Early onset hearing loss is frequently of genetic origin and usually caused by cochlear hair cell and/or neuronal malfunction. Associated heart and hearing abnormalities may be found in different syndromes, frequently in association with diseases of other organs, but cardio-auditory diseases [1] in the absence of other organ involvement are rare. A typical example is Jervell and Lange-Nielsen syndrome, characterized by congenital deafness, long QT and cardiac arrhythmias, but “normal” cardiac structure. In 2000, Schonberger et al. [1] reported two families with many members affected by sensorineural hearing loss, which occurred mostly in early adulthood and preceded the appearance of dilated cardiomyopathy (DCM), which usually occurred in the fourth decade [1]. The cardiac involvement in these patients was severe and was the cause of death or it necessitated a heart transplant, in all affected patients. Schonberger et al. [1] considered the gene encoding epicardin (a transcription factor expressed in the myocardium and the cochlea) to be a candidate gene, but a specific mutation was not identified. In a later study, Schonberger et al. [2] found a deletion in the EYA4 gene, which was present in all affected family members and absent in 300 control chromosomes. In contrast to the sarcomeric/cytoskeletal genes involved in DCM that encode structural proteins, EYA4 encodes a transcriptional coactivator.