New Imaging Findings of Incomplete Partition Type III Inner Ear Malformation and Literature Review

DISCUSSION

X-linked nonsyndromic deafness has been estimated to contribute only 1%–5% of genetic nonsyndromic deafness.² DFNX2 is the most common form of X-linked nonsyndromic deafness, which accounts for approximately 50% of all families with X-linked nonsyndromic deafness.² Most interestingly, DFNX2 is the only form of X-linked deafness to show anatomic anomalies on CT of the temporal bone.² Sennaroglu et al⁴ considered these anomalies as a type between incomplete partition type I (cystic cochleovestibular malformation) and incomplete partition type II (classic Mondini deformity) and called it IP-III. The term IP-III could help radiologists better understand this rare and characteristic type of deformity in the comprehensive classification of inner ear malformations. Choi et al¹⁰ identified IP-III in 10 (4.8%) of 206 patients with inner ear abnormalities in their research. Sennaroğlu and Bajin⁸ reported that IP-III constituted 2% of inner ear malformations in their data base. In our case series, it only accounted for 0.9%. IP-III mainly occurs in males, but female carriers may have milder forms of some characteristic findings.^6,11,12

Phelps et al³ first reported the following characteristic CT findings: bulbous IACs, incomplete separation of the basal turn of the cochleae from the fundi of the IAC, and wide first and second parts of the intratemporal facial nerve canals. Talbot and Wilson⁵ later added absence of the bony modiolus, an abnormal VA, and a dilated singular nerve canal. Sennaroglu¹³ noted that the otic capsule around the membranous labyrinth was thinner than normal. Saylisoy et al⁶ observed an enlarged VA with a cystic appearance and middle ear anomalies, including dysplasia at the oval and/or round window and stapes abnormalities such as a thickened footplate and single crus. Gong et al⁷ reported the stapes abnormalities, enlarged superior VN canal, and the cystic bulge in the superior vestibular margin. Anderson et al¹⁴ described the cystic changes in the SCC and vestibule, and they also reported a potential association between IP-III and hypothalamic hamartoma.

This case series demonstrates that the entire bony labyrinth, otic capsule, and IAC are all involved in IP-III. A dilated IAC at the lateral end and absence of modiolus with interscalar septa present are the most typical imaging findings. The size of the cochlea is slightly smaller, especially in the middle turn width, but the upper turn height is within the normal range. Although the cochlear cavity appears to be empty on CT, a hypointense spiral structure can be observed on MR imaging. This structure probably represents the membranous labyrinth, which extends into the dilated IAC due to the incomplete separation of the cochlear base from the IAC, and correspondingly, the branches of the CN can also be observed in the IAC. The enlarged superior VN canal has some noteworthy details as well. Because the superior VN has several branches from the ampullae of superior and lateral SCC and the utricle, the enlarged bony canals of some of these small branches can also be seen in some cases. An irregular vestibule with a cystic appearance is also a very common imaging finding, which could be seen in about 90% of our cases, and a cystic appearance of the SCC was present in nearly half of our patients. A slightly enlarged VA with a cystic appearance can also be observed in some cases. These cystic bulges show the same signal as the inner ear fluid on MR imaging. Dysplasia of the oval and round windows is also common, and the stapes footplate is sometimes involved.

DFNX2 hearing loss is due to loss of function of the POU3F4 protein.² The POU3F4 gene is expressed in early embryos in the otic capsule, which is involved in mesenchymal-mesenchymal signaling for the development of the inner ear.² During the inner ear development of the mouse, the Brn4/Pou3f4 gene product is initially detected in the ventral aspect of the otic capsule and later throughout the otic capsule in the mesenchyme of both the cochlear and vestibular aspects.¹⁵ The subcellular localization of the Brn4/Pou3f4 gene product also changes during the differentiation of the otic capsule. It remains nuclear in those regions of the otic capsule that eventually give rise to the mature bony labyrinth. However, the subcellular localization of the product shifts from strictly nuclear to perinuclear in those regions of the otic capsule that will cavitate to form acellular regions in the temporal bone, such as the scala tympani, scala vestibuli, and the internal auditory meatus.¹⁵ Brn4/Pou3f4-deficient mice also show very similar anomalies to those in human DFNX2.¹⁶ Most of the phenotypic features of these mutant animals result from the reduction or thinning of the bony compartment of the inner ear, including malformations of the stapes, cochlea, IAC, and superior SCC.¹⁵

The abnormal development of the otic capsule should be the key factor in these malformations in IP-III. It may lead to a thin otic capsule, absence of the bony modiolus, enlarged nerve canals in the IAC fundus, dysplastic oval and round windows, and an abnormal stapes footplate as well. Sennaroglu¹³ reported that the thin otic capsule may be formed by a thick endosteal layer, and probably the second and third layers are either absent or very thin instead of the usual 3 layers. It may not be possible to observe the normal endosteal layer or differentiate these 3 layers on CT with today’s level of radiologic precision. However, we still observed hypodense areas in the region of the fissula ante fenestram in the thin otic capsule in most of our young patients, which are prevalent among healthy children.¹⁷ This pericochlear hypodensity suggests that the thin otic capsule may have >1 layer. With respect to the cystic changes of the vestibule, SCC, and VA, we speculate that they might be caused by the abnormal development of the perilymphatic space.

The disadvantage of this case series is that we did not perform genetic analyses. However, the diagnosis of IP-III can be established with typical imaging features. Radiologists should be familiar to these imaging features, thereby preventing harmful interventions and providing proper genetic counseling.