Histopathology of nonsyndromic autosomal dominant midfrequency sensorineural hearing loss

Abstract

Background: Autosomal dominant, nonsyndromic, midfrequency sensorineural hearing loss (SNHL) is a well-known clinical entity. There are no reported histopathologic studies of temporal bones from individuals with such a hearing loss.

Objectives: To describe the otopathology in 2 affected individuals from 2 different kindreds with nonsyndromic, dominant, midfrequency SNHL.

Material and methods: Both subjects belonged to multigenerational families with nonsyndromic, autosomal dominant SNHL showing a cookie-bite pattern. Temporal bones were removed at autopsy and studied by light microscopy. Cytocochleograms were constructed for hair cells, stria vascularis, and cochlear neuronal cells.

Results: Subject 1 (a 77-yr-old man) from Kindred A was diagnosed in early childhood with an SNHL that was progressive, reaching profound levels by adulthood. Both cochleae showed complete loss of inner and outer hair cells, moderate to severe diffuse atrophy of the stria vascularis, and severe loss of cochlear neurons, including the peripheral dendrites. The hearing loss in Subject 2 (an 82-yr-old man from Kindred B) began in late childhood, was slowly progressive, and involved the higher frequencies later in life. Histopathology showed loss of outer and inner hair cells in the basal turn of the cochlea, moderate to severe loss of stria vascularis, but relative preservation of peripheral dendrites and cochlear neurons.

Conclusion: The main histopathologic abnormalities were loss of hair cells, stria vascularis, and cochlear neurons in 1 case and loss of hair cells and stria vascularis in the second case. Our results are consistent with the hypothesis that dysfunction and loss of hair cells may have been the primary histopathologic correlate for the midfrequency hearing losses in these 2 subjects.

FIG. 1

Subject 1 from Kindred A with autosomal dominant, nonsyndromic, midfrequency SNHL. A, Pedigree showing affected and nonaffected individuals in 3 generations. Affected individuals develop a midfrequency hearing loss in early childhood with mild-moderate-mild pattern on audiometric testing. They do not complain of vertigo. The propositus (Subject 1) was a 77-year-old man whose hearing loss was detected in early childhood. The hearing loss was progressive and reached severe to profound levels by the age of 50 years. B, Audio cytocochleograms of right and left ears of Subject 1. Audiometric thresholds at ages 39 and 73 years are shown. Speech discrimination could not be tested (CNT). The black areas in the cytocochleograms represent missing or abnormal elements. Inner hair (IHC) and outer hair cells (OHC) are shown as present (white) or absent (black). Vertical axes of the cytocochleogram for the stria vascularis and cochlear neurons represent percentage of loss. Neuronal counts were compared with age-matched controls. Both ears showed complete loss of inner and outer hair cells, severe atrophy of the stria vascularis, and severe loss of cochlear neurons. C, Histopathology of right cochlea of Subject 1. There was diffuse atrophy of the organ of Corti, severe atrophy of the stria vascularis, and severe loss of cochlear neurons.

FIG. 2

Subject 2 from Kindred B with autosomal dominant, nonsyndromic, midfrequency SNHL. A, Pedigree showing affected and nonaffected individuals in 5 generations. Affected individuals develop a midfrequency hearing loss in late childhood with slow progression. Later in life, the audiometric pattern becomes flat, with impaired hearing in the higher frequencies. The propositus (Subject 2) was an 82-year-old man who developed hearing loss in late childhood and wore amplification from approximately the age of 55 years. B, Audio cytocochleograms of right and left ears of Subject 2. Audiometric thresholds were analyzed at age 71 years, 11 years before death (test autopsy interval [TAI]). The right ear showed a severe to profound downsloping SNHL, whereas the left ear showed a moderate to severe midfrequency hearing loss. Speech discrimination was 80% on the right and 30% on the left. The cytocochleograms showed complete loss of outer and inner hair cells in the 0- to 19-mm region, with partial loss of outer hair cells in the remainder of the cochlea. There was moderate to severe atrophy of the stria vascularis. However, there was only a mild loss of cochlear neurons. C, Section from right cochlea of Subject 2. There was atrophy of the organ of Corti and moderate to severe atrophy of the stria vascularis. There was a relatively good population of cochlear neurons within Rosenthal canal (compare with Fig. 1C). The saccule was normal.