Audiological and surgical evidence for the presence of a third window effect for the conductive hearing loss in DFNX2 deafness irrespective of types of mutations

Abstract

The objective of this study was to clarify the cause of the air-bone gap in incomplete partition (IP) type III cases according to the POU3F4 gene (DFNX2) mutation type. A retrospective analysis of patient medical records was done in a tertiary referral medical center. Five IP type III patients proved to be carrying a mutation in or affecting POU3F4. The hearing and the middle ear status at either exploratory tympanotomy or cochlear implantation from these DFNX2 cases was reviewed. Four of five unrelated IP type III patients harbored a point mutation of POU3F4 and the fifth patient carried a large genomic deletion upstream to POU3F4. Two of the four DFNX2 patients carrying a point mutation had moderate to severe mixed hearing loss with a substantial amount of air-bone gap. These patients underwent exploratory tympanotomy to identify the cause of their hearing loss. The other three patients, including one carrying a large deletion, had profound hearing loss at presentation and received a cochlear implant. In the exploratory tympanotomy group with a substantial amount of air-bone gap and a point mutation (n = 2), one patient had a perfect ossicular chain with normal mobility, a positive ipsilateral stapedial reflex, and a positive round window reflex. In the cochlear implantation group (n = 3), we found a stapes with normal mobility and a positive round window reflex in one patient who harbored a large genomic deletion upstream to POU3F4. We concluded that the probable presence of the third window effect is not limited to the particular type of POU3F4 mutation.

Audiological and Radiological Characteristics in Incomplete Partition Malformations

“…In IP-II and IP-III patients, the IAC does not appear to cause the pathology, and therefore, the cochlear nerve is normal in IP-II and IP-III patients [7] . Consistent with previous studies, the present study noted the presence of severe to profound MHL in all IP-III patients [12,14,15] . Among these studies, Choi et al [14] stated that the conductive component found in IP-III malformations is related to the pathologic third window.…”

“…Consistent with previous studies, the present study noted the presence of severe to profound MHL in all IP-III patients [12,14,15] . Among these studies, Choi et al [14] stated that the conductive component found in IP-III malformations is related to the pathologic third window. A recent paper by Sennaroğlu [7] .…”

“…Many studies have analyzed the audiological findings of IEMs [2,10,[12][13][14][15][16][17][18] . This study, however, is the first paper to compare the audiological and radiological findings of patients diagnosed with IP malformations.…”

A New Classification of Cochleovestibular Malformations and Implications for Predicting Speech Perception Ability after Cochlear Implantation

“…X-linked stapes gusher syndrome was first reported in 1971 [Nance et al, 1971]. It was considered as an independent disease entity in many reports [Choi et al, 2013], and the original classifications of CVMs did not include this syndrome [Jackler et al, 1987;Sennaroglu and Saatci, 2002]. In 2006, Sennaroglu et al suggested that the radiological phenotype of X-linked stapes gusher syndrome be called incomplete partition type III [Sennaroglu et al, 2006].…”

“…There is also a difference in pathogenesis between X-linked stapes gusher syndrome and other types of CVM. Most CVMs are thought to be caused by arrested or aberrant development during inner ear embryogenesis, but Xlinked stapes gusher syndrome is caused by a mutation in the POU3F4 gene on the X chromosome [Choi et al, 2013]. Therefore, X-linked stapes gusher syndrome is much better considered separately from other types of CVM because of its different audiological nature and different pathogenesis.…”