variation in RELN gene. Loci include: Pathophysiology The pathophysiology of otosclerosis is complex. The key lesions of otosclerosis are multifocal areas of sclerosis within the endochondral temporal bone. These lesions share some characteristics with Paget's Disease, but they are not thought to be otherwise related. Histopathological studies have all been done on cadaveric temporal bones, so only inferences can be made about progression of the disease histologically. It seems that the lesions go through an active "spongiotic" or hypervascular phase before developing into "sclerotic" phase lesions. There have been many genes and proteins identified that, when mutated, may lead to these lesions. Also there is mounting evidence that measles virus is present within the otosclerotic foci, implicating an infectious etiology (this has also been noted in Paget's Disease). Conductive hearing loss (CHL) in otosclerosis is caused by two main sites of involvement of the sclerotic (or scar-like) lesions. The best understood mechanism is fixation of the stapes footplate to the oval window of the cochlea. This greatly impairs movement of the stapes and therefore transmission of sound into the inner ear ("ossicular coupling"). Additionally the cochlea's round window can also become sclerotic, and in a similar way impair movement of sound pressure waves through the inner ear ("acoustic coupling"). CHL is usually concomitant with impingement of abnormal bone on the stapes footplate. This involvement of the oval window forms the basis of the name fenestral otosclerosis. The most common location of involvement of otosclerosis is the bone just anterior to the oval window at a small cleft known as the fissula ante fenestram. The fissula is a thin fold of connective tissue extending through the endochondral layer, approximately between the oval window and the cochleariform process, where the tensor tympani tendon turns laterally toward the malleus. The mechanism of sensorineural hearing loss in otosclerosis is less well understood. It may result from direct injury to the cochlea and spiral ligament from the lytic process or from release of proteolytic enzymes into the cochlea. There are certainly a few well documented instances of sclerotic lesions directly obliterating sensory structures within the cochlea and spiral ligament, which have been photographed and reported post-mortem. Other supporting data includes a consistent loss of cochlear hair cells in patients with otosclerosis; these cells being the chief sensory organs of sound reception. A suggested mechanism for this is the release of hydrolytic enzymes into the inner