Extralabyrinthine manifestations of DFNA9.
DFNA9 is an autosomal dominant cause of non-syndromic adult-onset sensorineural hearing loss with associated variable vestibular dysfunction caused by mutations in the COCH gene. DFNA9 has previously been characterized by the presence of unique histopathologic features limited to the cochlear and vestibular labyrinth. This report describes newly discovered extralabyrinthine findings within the middle ear in DFNA9 and discusses their implications. The histopathologic anatomy of extralabyrinthine structures was reviewed in 12 temporal bones from seven individuals with DFNA9 and compared with age-matched controls. All temporal bones with DFNA9 had abnormal deposits within the tympanic membrane, incudomalleal joint, and incudostapedial joint. Hematoxylin and eosin stain and Movat's pentachrome stain both revealed different staining patterns of the extralabyrinthine deposits compared with the intralabyrinthine deposits suggesting that the composition of the deposits varies with location. The deposits within the tympanic membrane resembled cartilage morphologically and stained positively for aggrecan, an extracellular matrix protein found in cartilage. However, the cellular component of the tympanic membrane deposits did not stain with immunomarkers for chondrocytes (s100 and connective tissue growth factor). These novel findings in DFNA9 have implications for the phenotypic expression of the disorder and the clinical workup of adult-onset sensorineural hearing loss.
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. mccallaa@upmc.edu
Andrew A
AA
McCall
Fred H
FH
Linthicum
Jennifer T
JT
O'Malley
Joe C
JC
Adams
Saumil N
SN
Merchant
Marc K
MK
Bassim
Robert
R
Gellibolian
Jose N
JN
Fayad
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D007758:Ear, Inner / Q000378:metabolism / Q000473:pathology; D004432:Ear, Middle / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013701:Temporal Bone / Q000378:metabolism* / Q000473:pathology; D014432:Tympanic Membrane / Q000378:metabolism* / Q000473:pathology
C110668:COCH protein, human; D016326:Extracellular Matrix Proteins; D011506:Proteins