Mondini Deformity

Embryology

Typically, the membranous labyrinth achieves its usual shape around the eighth week of development, and ossification of the otic capsule around the membranous labyrinth is complete by birth. Traditionally, pathogenesis of cochlear malformations was believed to be related to different stages of developmental arrest during inner-ear formation. Based on this rationale, developmental arrest at the seventh week of gestation produces a cochlea that is smaller and incompletely partitioned with only 1.5 turns. ^[6] However, recent evidence demonstrates that not all inner-ear anomalies result from developmental arrest at a specific date. ^[2]

Classification

In 1987, Jackler et al proposed a classification system of inner-ear malformations that was based on specific dates of cessation of cochlear development. Cessation of development at the fifth week caused cochlear agenesis, cessation at the sixth week produced cochlear hypoplasia, and developmental cessation at the seventh week produced a small cochlea that was incompletely partitioned with resultant 1.5 turns. ^[6] This classification system was created using polytomography, a form of imaging that has now been discarded and since replaced with high-resolution CT imaging, which is superior in its resolution to polytomography.

In 2004, Sennaroglu and Saatci created a modified classification system for incomplete partition of the cochlea to help differentiate different forms of incomplete partitioning. ^[7] Using a retrospective review of temporal bone CT scans from patients with sensorineural hearing loss, the researchers were able to ascertain two variants in the their study population.

The first variant, termed incomplete partition type I (IP-I), demonstrated a cochlea that was without the entire interscalar septum and the modiolus, resulting in a cystic appearance. While the vestibule was found to be dilated when compared to a normal temporal bone, enlargement of the vestibular aqueduct was rare.

Incomplete partition type II (IP-II) demonstrated a cochlea that had a normal basal turn; however, the apex was cystic in appearance owing to absence of the modiolus and the corresponding interscalar septum. Additionally, the vestibule was mildly dilated and the vestibular aqueduct was enlarged. The IP-II malformation is the deformity described by Carlo Mondini and is the basis for the title Mondini deformity.

A third type of incomplete partition (IP-III) has been recently described and is found in individuals with X-linked deafness. Morphologically IP-III demonstrates the presence of the interscalar septa; however, the modiolus is absent. ^[8]

In all three variants of incomplete partitioning, the cochleas are of normal size, which differs from the findings of Jackler et al in 1987. Additionally, Sennaroglu and Saatci state that using the term 1.5 turns for Mondini deformity is inaccurate and should be discontinued. The reasoning is that, if the cochlea has 1.5 turns, then it would technically be smaller than a normal cochlea, which would place it into the category of cochlear hypoplasia rather than incomplete partitioning. ^[6]

Schematic representation of the normal cochlea and cochlear malformations. A: normal cochlea, mid-modiolar section; Mo = modiolus, CA = cochlear aperture, B = basal turn, M = middle turn, A = apical turn, arrowheads = interscalar septa. B: Normal cochlea, inferior section passing through the round window niche (RWN); arrowhead = interscalar septum between middle and apical turns. C: Cochlear aplasia with normal vestibule. D: Cochlear aplasia with enlarged vestibule. E: Common cavity. F: Incomplete partition type I. G: Incomplete partition type II. H: Incomplete partition type III. I: Cochlear hypoplasia, bud type (type I). J: Cochlear hypoplasia, cystic cochlea type (type II). K: Cochlear hypoplasia, with less than 2 turns (type III).

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Genetics

Mutation of the SLC26A4 gene, which codes for the membrane transport protein pendrin and functions as an iodide/chloride transporter, has been implicated in congenital hearing loss. ^{[9, 10]} Mutation of the SCL26A4 gene is very heterogeneic, with more than 100 different mutations identified, including missense, nonsense, and splice-site mutations. ^[11]

The SCL26A4 mutation has been associated with Pendred syndrome and DFNB4, both of which share sensorineural hearing loss associated with Mondini deformity or an enlarged vestibular aqueduct. ^{[12, 13, 14, 15]}  Typically, individuals with Pendred syndrome are homozygous for the SCL26A4 mutation and display incomplete partition type II or an enlarged vestibular aqueduct. ^[16]

A study by Forli et al indicated that biallelic SLC26A4 mutations are associated with worse hearing thresholds; the biallelic mutations also carry a greater likelihood that thyroid pathologies and Mondini malformations are present than is isolated enlarged vestibular aqueduct. These effects particularly accompany homozygous mutations. ^[17]

Not all congenital malformations of the inner ear result from SCL26A4 gene mutation. ^[18] This is an interesting finding because the various types of cochlear malformation have always been thought of as a continuum of defects, all due to developmental arrest at some embryological stage.

In persons with IP-III, X-linked deafness has been found to be related to the pathogenesis. Males with X-linked deafness are expected to suffer from severe hearing loss, while females are expected to experience more mild-to-moderate hearing loss. ^[19]

Current estimates of the prevalence of congenital SNHL are between 1 and 6 newborns per 1,000. 20-30% of patients with congenital hearing loss demonstrate some sort of radiographically anomalous inner ear. ^{[6, 19, 3]} A study of 63 patients with SNHL and radiographically documented abnormalities found that 55% of these patients had incomplete partitioning of the cochlea. ^[6]

The prognosis of Mondini deformity varies. Depending on the degree of malformation of the cochlea, sensorineural hearing loss can range from nonexistent to profound.