Developmental study of the long QT with deafness syndrome in the chick embryo: cochlear pathology

Developmental abnormalities of the peripheral auditory structures in an experimental animal model of the cardio-auditory (long QT with deafness) syndrome are described. Prolonged QT intervals in the electrocardiogram and deafness were induced in chick embryos by removal of tissue in the region of the right nodose and otic placodes on the first day of incubation. Electrocardiographic recordings, cochlear potential and brainstem auditory evoked responses were recorded in late embryonic life (E17), and used to identify embryos with long QTs and deafness. External and middle ears were evaluated under a dissecting microscope. Inner ears were evaluated in histological sections. Anomalies of the external and middle ears, such as the external auditory meatus, tympanic membrane and stapes, were attributed to disturbance of neural crest development. Anomalies of the inner ear, such as a complete absence of the cochlear duct and auditory nerve, or decreased length of the basilar papilla, were attributed to disturbance of otic placode development. The fact that a small lesion in the region of the nodose and otic placodes during early development in the chick animal model can produce a long QT interval in the electrocardiogram and deafness suggests that abnormal development in this region early in development might be the underlying cause of the human syndrome.