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Temporal Bone Histopathology in Alport Syndrome
Author(s) -
Merchant Saumil N.,
Burgess Barbara J.,
Adams Joe C.,
Kashtan Clifford E.,
Gregory Martin C.,
Santi Peter A.,
Colvin Robert,
Collins Bernie,
Nadol Joseph B.
Publication year - 2004
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200409000-00020
Subject(s) - organ of corti , basilar membrane , alport syndrome , basement membrane , pathology , cochlea , type iv collagen , sensorineural hearing loss , temporal bone , anatomy , inner ear , hearing loss , glomerular basement membrane , histopathology , biology , medicine , extracellular matrix , laminin , microbiology and biotechnology , kidney , glomerulonephritis , endocrinology , audiology
Abstract Objective: To determine the histopathologic abnormalities within the cochlea in Alport syndrome. Background: Alport syndrome, which manifests as hereditary nephritis and sensorineural hearing loss (SNHL), is caused by mutations in genes that code for the ∝3, ∝4, and ∝5 chains of type IV collagen. The ∝3, ∝4, and ∝5 chains of type IV collagen are present in the basement membrane of the organ of Corti. Previous temporal bone studies have failed to identify histopathologic correlates for the SNHL. Methods: We examined temporal bones from nine individuals with a clinical diagnosis of Alport syndrome. One of our cases also had genetic testing that showed a mutation in the type IV collagen ∝5 chain gene. Results: By light microscopy, eight of nine cases demonstrated two unique pathologic changes: 1) a “zone of separation” between the basilar membrane and overlying cells of the organ of Corti and 2) presence of cells filling the tunnel of Corti and extracellular spaces of Nuel. The cytologic losses of hair cells, stria vascularis, and cochlear neuronal cells were insufficient to account for the observed SNHL in our cases. Electron microscopy was performed in four cases; all four demonstrated the following: 1) the zone of separation that was observed at light microscopy occurred between the basement membrane and the basilar membrane, 2) the cells within the tunnel of Corti and spaces of Nuel were morphologically similar to supporting cells, and 3) the basement membrane of strial capillaries and the spiral vessel (under the basilar membrane) were normal. Conclusions: The histopathologic correlates of cochlear involvement in Alport syndrome are abnormalities of the basement membrane of cells of the organ of Corti and dysmorphogenesis (cellular infilling of the tunnel and extracellular spaces) of the organ of Corti. We hypothesize that these abnormalities result in SNHL by altering cochlear micromechanics.