A New Pathogenic Variant in POU3F4 Causing Deafness Due to an Incomplete Partition of the Cochlea Paved the Way for Innovative Surgery

Abstract

Incomplete partition type III (IP-III) is a relatively rare inner ear malformation that has been associated with a POU3F4 gene mutation. The IP-III anomaly is mainly characterized by incomplete separation of the modiolus of the cochlea from the internal auditory canal. We describe a 71-year-old woman with profound sensorineural hearing loss diagnosed with an IP-III of the cochlea that underwent cochlear implantation. Via targeted sequencing with a non-syndromic gene panel, we identified a heterozygous c.934G > C p. (Ala31Pro) pathogenic variant in the POU3F4 gene that has not been reported previously. IP-III of the cochlea is challenging for cochlear implant surgery for two main reasons: liquor cerebrospinalis gusher and electrode misplacement. Surgically, it may be better to opt for a shorter array because it is less likely for misplacement with the electrode in a false route. Secondly, the surgeon has to consider the insertion angles of cochlear access very strictly to avoid misplacement along the inner ear canal. Genetic results in well describes genotype-phenotype correlations are a strong clinical tool and as in this case guided surgical planning and robotic execution.

Cochlear Size Assessment Predicts Scala Tympani Volume and Electrode Insertion Force- Implications in Robotic Assisted Cochlear Implant Surgery

“…Personalized treatment in cochlear implantation is being developed at multiple timepoints throughout the patient's journey, for instance during audio processor fitting (6) and otological pre-planning software (e.g., OTOPLAN R ) in assessing cochlear size and choosing electrode array length matching the cochlear size (7). Robotic assisted CI surgery and controlled speed electrode array insertion, such as the HEARO R system and ROBOTOL R , respectively (8)(9)(10) are in the early stages of clinical practice. To complement these technological advancements and to take the concept of personalized CI treatment to the next level where the electrode insertion speed can be personalized to the individual's ST size and volume, a study on the following objectives is essential.…”

Cochlear implantation in a Chinese patient with a novel frameshift variant in POU3F4 gene and incomplete partition type III: a case report

“…Cerebrospinal fluid gushing during cochlear implantation has been previously reported in patients with IP-III caused by a POU3F4 gene mutation, and profuse CSF gushing has also been observed. 10 Intraoperative repair and early postoperative detection are important factors in avoiding serious complications. The electrode arrays may be inserted via cochleostomy or a round window, and muscle tissue should be used to seal the site after electrode insertion to avoid post-operative CSF leakage or meningitis.…”

Sordera neurosensorial congénita con malformación de oído interno ligada al X en una familia mexicana

“…Es una MOI poco frecuente, [10][11][12] y se puede distinguir la cóclea y el vestíbulo. Presenta un septo interescalar con un modiolo ausente, las medidas de la cóclea son normales, tiene un aspecto quístico, sin arquitectura interna, y el vestíbulo se encuentra dilatado.…”

“…La cóclea se localiza directamente lateral al conducto auditivo interno (CAI), el cual es "bulboso" o dilatado, con una separación incompleta de las espirales de la cóclea, y ambos están ampliamente comunicados por una deficiencia completa de la lámina cribosa. La cápsula ótica es más delgada alrededor del laberinto membranoso, en comparación con una cóclea normal [7,[9][10][11][12]. La PI-III es una de las MOI menos frecuentes; también, entre los grupos de partición incompleta.…”

“…La PI-III es una de las MOI menos frecuentes; también, entre los grupos de partición incompleta. Se observa en el 2% de todas las malformaciones cocleares, de herencia ligada al cromosoma X. Típicamente afecta a los hombres y cursa con hipoacusia mixta rápidamente progresiva [10][11][12][13]. Se ha asociado frecuentemente con una variante patogénica del gen POU3F4, y en algunos casos variantes del gen COL4A6 [7,8,[10][11][12][13].…”