RESUMEN

PURPOSE: This study assessed whether the Fazekas score could account for the variability in cochlear implantation (CI) outcomes among individuals with DFNA9 and evaluated signal loss in the semicircular canals (SCCs) on magnetic resonance imaging (MRI) among individuals with DFNA9. METHOD: This retrospective cross-sectional study included CI recipients with DFNA9. Pre-implantation MRI-scans were reviewed to determine the Fazekas score, localizing and grading cerebral white matter lesions (WML), and identify abnormalities in the SCCs. CI performance was assessed by evaluating phoneme scores one year post-implantation. The function of the SCCs was evaluated using rotatory chair testing with electronystagmography (ENG) and the video Head Impulse Test (vHIT). RESULTS: Forty-five subjects (49 ears) were enrolled. The phoneme scores significantly improved from 35% (IQR 11-50) pre-implantation to 84% (IQR 76-90) one year post-implantation. No correlation was observed between the Fazekas score and the one-year post-implantation phoneme score (rsp=0.003, p = 0.986). Signal loss in at least one SCCs was detected in 97.7% of subjects and 77.8% of ears. There was no correlation between vestibular test results and fluid signal loss in the SCCs on MRI. CONCLUSION: Most individuals with DFNA9 show improved speech recognition with CI. The observed variability in CI outcomes was not linked to the Fazekas score. Additionally, our study confirms a high prevalence of focal sclerosis in DFNA9. Recognizing the limitations of this study, further research is needed to explore the predictive role of the Fazekas score on CI outcomes and its relationship with vestibular function.

RESUMEN

OBJECTIVE: to report the first case series of Brazilian children diagnosed with Kleefstra syndrome, present a possible phenotype expansion to the syndrome and to raise physicians' awareness for this rare disease. RESULTS: seven patients with confirmed KS were evaluated, including 5 males and 2 females. Abnormal prenatal findings were observed in 4 patients. Most patients were born at term, with normal birth measurements. All patients had neurodevelopmental delay and 6 evolved with intellectual disability. Hearing loss was present in 57.1% of patients and 28.7% had congenital heart disease. In males, cryptorchidism was present in 75%. Despite the facial dysmorphisms, only 2 out of 7 patients had a pre-test clinical suspicion of KS. One specific patient presented bilateral agenesis of the semicircular canals, a very rare ear manifestation in Kleefstra syndrome, representing a possible phenotype expansion of the syndrome. CONCLUSION: this report aims to promote awareness among physicians evaluating patients in a context of neurodevelopmental delay or congenital malformations, especially congenital heart defects. We also highlight a possible phenotype expansion of the syndrome, with a case of semicircular anomaly, not reported in this syndrome so far.

RESUMEN

This study examines a case of lateral canal benign paroxysmal positional vertigo (BPPV) where the sequence of diagnostic positional maneuvers may have influenced the release of some canaliths into the utricle. Partial treatment during BPPV diagnostic maneuvers may complicate side identification during supine roll test, especially in canalolithiasis cases.

RESUMEN

Background: Meniere's disease (MD) is an ear-related vestibular disorder accompanied by vertigo, hearing loss, and tinnitus. The anatomical structure and spatial position of the semicircular canals are important for understanding vestibular function and disease; however, research on MD and the effect of anatomical changes in the semicircular canals is limited. This study explored the relationship between the spatial location of the semicircular canals and MD using ultra-high-resolution computed tomography (U-HRCT) and intelligent segmentation. Methods: Isotropic U-HRCT images obtained from patients with MD and healthy controls (HCs) were retrospectively analyzed. We extracted the semicircular canal structures and extracted their skeleton. The plane of the skeleton of each semicircular canal was fitted separately. The mutual angles between the semicircular canals, and the angles between each semicircular canal and each plane of the coordinate system were measured. Results: Among 45 MD-affected ears (MDAEs), 33 MD-healthy ears (MDHEs), and 45 HC ears, the angle between the superior and lateral semicircular canals (LSCs) and the angle between the superior and posterior semicircular canals (PSCs) were larger in the MDAE and MDHE groups than the HC group (P<0.01), while the angle between the posterior and LSCs was smaller in the MDAE group than the HC group (P<0.001). The angles between the superior and PSCs and coronal plane (CP) of the coordinate system were significantly smaller in the MDAE and MDHE groups than the HC group (P<0.01); however, the angles between the LSC and axial plane and CP were significantly larger in the MDAE and MDHE groups than the HC group (P<0.001). Conclusions: Spatial position changes in the semicircular canals may be the anatomical basis of MD.

RESUMEN

Objectives: Even though BPPV is one of the most common causes of vertigo, it is often underdiagnosed and omitted in the diagnosis of patients reporting vertigo. The aim of the study was to establish a diagnostic pattern useful in patients admitted due to vertigo, based on the most common clinical characteristics of patients suffered from posterior canal BPPV (PC-BPPV), horizontal canal BPPV with geotropic (HCG-BPPV) and apogeotropic nystagmus (HCA-BPPV). Methods: The analysis covered the results obtained in 105 patients with a positive result of the Dix-Hallpike maneuver or the supine roll test. The patients were divided into 3 groups based on the BPPV type: gr.1:PC-BPPV (60%); gr.2: HCG-BPPV (27%); gr.3: HCA-BPPV (13%). Patients before the diagnostic maneuvers filled the questionnaire concerning their symptoms and previous diseases. Results: Almost all patients had vertigo during turning over in bed and the character of the symptoms was paroxysmal. The answers to questions about the type of head movement evoked vertigo and how long vertigo lasted were differentiating. The percentages of correct diagnosis speculated by the combined answers were 69.6% in PC-BPPV, 61.8% in HCG-BPPV, and 80% in HCA-BPPV. Conclusions: Basing on those observations there is presented the diagnostic schedule which could be useful in dizziness examination. The above results indicate that a properly collected interview with the patient allows for a high percentage of accurate diagnosis.

RESUMEN

We report an extremely rare case with bilateral horizontal semicircular canal (HSC) dysplasia presenting as hearing loss with recurrent vertigo mimicking Meniere's disease in a previously healthy 49-year-old male patient. HSC malformation is one of the common isolated developmental anomalies of the bony labyrinth usually associated with varying degree of hearing loss. He suffered from recurrent episodes of vertigo lasting more than 20 minutes accompanied by left hearing loss and tinnitus for 3 years. Pure-tone audiometry revealed a mild to moderate hearing loss at low frequencies in the left ear. Bithermal caloric testing revealed significant left-sided canal paralysis, but other vestibular testing was normal. Computerized tomography (CT) of the temporal bone showed the left HSC hypoplasia lacking a central bony island fused together with an enlarged vestibule, and right dysplasia, finally diagnosed with bilateral HSC dysplasia. Meniere's disease-like recurrent vertigo attack and hearing loss were suspected to be caused by subsequent endolymphatic hydrops which could be due to HSC dysplasia.

RESUMEN

During inner ear semicircular canal morphogenesis in zebrafish, patterned canal-genesis zones express genes for extracellular matrix component synthesis. These include hyaluronan and the hyaluronan-binding chondroitin sulfate proteoglycan Versican, which are abundant in the matrices of many developing organs. Charged hyaluronate polymers play a key role in canal morphogenesis through osmotic swelling. However, the developmental factor(s) that control the synthesis of the matrix components and regulation of hyaluronate density and swelling are unknown. Here, we identify the transcription factor, Lmx1b, as a positive transcriptional regulator of hyaluronan, Versican, and chondroitin synthesis genes crucial for canal morphogenesis. We show that Versican regulates hyaluronan density through its protein core, whereas the charged chondroitin side chains contribute to the osmotic swelling of hyaluronate. Versican-tuned properties of hyaluronate matrices may be a broadly used mechanism in morphogenesis with important implications for understanding diseases where these matrices are impaired, and for hydrogel engineering for tissue regeneration.

RESUMEN

PURPOSE: The most used neurosurgical approach to reach cerebellar-pontine angle is the retrosigmoid route. This article describes the presigmoid approach which requires excellent knowledge of the labyrinthine block together with quantitative analysis of temporal bone CT. METHODS: CT-based quantitative measurements were obtained in patients undergoing vestibular neurectomy with a presigmoid approach. Eighteen patients were enrolled, and five measures were taken: Trautmann's area, the petro-clival angle, presigmoid dura length and its angle. The relationship between these measurements and hospitalization days, operating times, and complications was explored. RESULTS: The posterior semicircilar canal (PSC)-sigmoid sinus (SS) distance, presigmoid dura- internal auditory canal (IAC)-PSC angle, and duration of surgery are predictors of complications. Specifically, a PSC-sigmoid sinus distance <11 mm, a dura presig-IAC-PSC angle <14 are associated with the highest risk of complications. CONCLUSION: Preoperative temporal bone CT scan can guide the surgeon through the narrowest areas of the surgical approach. Trautmann's triangle area and petro-clival angle reduction are challenging and can be faced with combined microscopic-endoscopic technique, and with optics angulation-rotation. The retrolabyrinthine approach can enable hearing preservation and minimal cerebellar retraction.

RESUMEN

Introduction: Lateral semicircular canal (LSCC) dysplasia is the most common inner ear malformation. The severity of dysplasia can appear in various spectrums, from a short and broad LSCC with normal or small-sized central bony island (CBI) to a single fluid-filled cavity confluent with the vestibule without CBI. However, reports on the association between LSCC dysplasia and the loss of vestibular function are still lacking. In this study, the results of vestibular function tests [caloric test and video-head impulse test (vHIT)] in patients with LSCC dysplasia were analyzed and compared between groups with and without CBI. Methods: This study retrospectively enrolled 17 patients (23 ears) who had LSCC dysplasia following computed tomography or magnetic resonance imaging and underwent vestibular function tests. Results: LSCC dysplasia was observed unilaterally in 11 patients and bilaterally in six patients. Nine of 23 ears had CBIs, and 14 ears had no CBI. Three of 17 patients experienced dizziness. Abnormal caloric tests were detected in 11 of the 16 patients who underwent the caloric tests (69%); in contrast, 11 of 12 patients who underwent the vHIT (92%) had normal LSCC vestibulo-ocular reflex (VOR) gain on vHIT. A significant correlation was found between the maximum slow-phase velocity of the caloric test and LSCC VOR gain of the vHIT (correlation coefficient 0.792, p = 0.004). The CBI-absent group showed significantly lower SPV and LSCC VOR gains than the CBI-present group (p = 0.001 and 0.004, respectively). Discussion: LSCC dysplasia impairs VOR function, especially in the absence of CBI.

RESUMEN

INTRODUCTION: Gentamicin is a vestibulotoxic antibiotic often used in patients with Ménière's disease for its vestibular ablative effects. Gentamicin's effect on the horizontal semicircular canal does not always correlate with the degree of vertigo control achieved by patients; its effect on the vertical semicircular canals remains unknown. We sought to examine the effect of intratympanic gentamicin on vertical semicircular canal function in patients with Ménière's disease using video head impulse testing. METHODS: A retrospective case series was carried out at a tertiary academic center. Patients with Ménière's disease who received ≥1 intratympanic gentamicin injection from 2019-2022 and had video head impulse testing performed were included. Outcomes of interest were vertical semicircular canal function following intratympanic gentamicin, correlations between vertical semicircular canal function and horizontal semicircular canal function, and residual symptoms following injection. RESULTS: Ten patients met inclusion criteria. Twenty percent had abnormal V-SCC function prior to any injection and 40% following the first injection. There was an association between abnormal vertical and horizontal semicircular canal function following the first intratympanic gentamicin injection, though the relationship did not reach statistical significance (p = 0.058). While patients with abnormal vertical semicircular canal function following the first injection were less likely to report ongoing vertigo attacks, the relationship was not statistically significant (p = 0.260). CONCLUSIONS: Intratympanic gentamicin leads to changes in vertical semicircular canal function in at least a proportion of patients with Ménière's disease. Further study is required to better assess correlations between vertical semicircular canal function and symptom control following intratympanic gentamicin.

Asunto(s)

RESUMEN

SOX proteins are transcription factors which play a role in regulating the development of progenitor cells and tissue differentiation. Twenty members are known, clustered in eight groups named A through H and sharing a common DNA-binding domain called the HMG (high-mobility-group) box. Eleven of the SOX genes have been associated with genetic disorders so far, covering a broad spectrum of developmental diseases. SOX4 is a single-exon gene and belongs to the SOXC group, together with SOX11 and SOX12. SOX4 variants have been recently described to cause a highly penetrant but heterogeneous disorder, with a phenotypic spectrum ranging from mild developmental delays and learning difficulties to intellectual disabilities with congenital anomalies. Nineteen pathogenic variants have been reported to date, generally de novo, heterozygous, and inactivating, either stop-gain or missense, the latter ones primarily targeting the HMG domain. Further, a bi-allelic variant was reported in a single consanguineous family. Copy number variants leading to whole gene deletion or duplication are rare and not clearly associated with any neurodevelopmental disorder. Many open questions remain regarding the definition of variants of unknown significance, a possible role of missense variants outside the HMG domain, genotype-phenotype correlation, the range of phenotypic spectrum and modifying factors, and treatment options.

Asunto(s)

RESUMEN

Different head positions affect the responses of the vestibular semicircular canals (SCCs) to angular movement. Specific head positions can relieve vestibular disorders caused by excessive stimulating SCCs. In this study, we quantitatively explored responses of human SCCs using numerical simulations of fluid-structure interaction and vestibulo-ocular reflex (VOR) experiments under different forward-leaning angles of the head, including 0°, 10°, 20°, 30°, 40°, 50°, and 60°. It was found that the horizontal nystagmus slow-phase velocity and corresponding biomechanical responses of the cupula in horizontal SCC increased with the forward-leaning angles of the head, reached a maximum when the head was tilted 30° forward, and then gradually decreased. However, no obvious vertical or torsional nystagmus was observed in the VOR experiments. In the numerical model of bilateral SCCs, the biomechanical responses of the cupula in the left anterior SCC and the right anterior SCC showed the same trends; they decreased with the forward-leaning angles, reached a minimum at a 40° forward tilt of the head, and then gradually increased. Similarly, the biomechanical responses of the cupula in the left posterior SCC and in the right posterior SCC followed a same trend, decreasing with the forward-leaning angles, reaching a minimum at a 30° forward tilt of the head, and then gradually increasing. Additionally, the biomechanical responses of the cupula in both the anterior and posterior SCCs consistently remained lower than those observed in the horizontal SCCs across all measured head positions. The occurrence of these numerical results was attributed to the consistent maintenance of mutual symmetry in the bilateral SCCs with respect to the mid-sagittal plane containing the axis of rotation. This symmetry affected the distribution of endolymph pressure, resulting in biomechanical responses of the cupula in each pair of symmetrical SCCs exhibiting same tendencies under different forward-leaning angles of the head. These results provided a reliable numerical basis for future research to relieve vestibular diseases induced by spatial orientation of SCCs.

RESUMEN

PURPOSE: To determine the prevalence of benign paroxysmal positional vertigo without dizziness, a treatable falls risk factor in people attending outpatient falls clinics. METHODS: Over 6 years, 618 people at risk of falls attending 2 falls clinics were assessed for benign paroxysmal positional vertigo, whether dizzy or non dizzy. Data regarding demographics, canal location of positive tests and comorbidities were collected from medical records. RESULTS: Thirty-nine percent (238) of people with falls risk tested positive for benign paroxysmal positional vertigo; 62 (26%) or 1 in 4 of those testing positive were not dizzy. Thirty-nine of 104 (38%) testing positive for single canal benign paroxysmal positional vertigo and twenty-four of 134 (18%) testing positive for multiple canal benign paroxysmal positional vertigo were not dizzy. Comorbidities were common for all with falls risk but did not differentiate for benign paroxysmal positional vertigo on testing. CONCLUSIONS: Benign paroxysmal positional vertigo is common in people attending falls clinics and contributes to falls risk. Dizziness is common in BPPV though 26% or 1 in 4 people testing positive were not dizzy and would be missed without mandatory testing. Testing should also include all semicircular canals as multiple-canal involvement was high.

Benign paroxysmal positional vertigo is a common and treatable falls risk factor, however screening for benign paroxysmal positional vertigo in people who fall usually only occurs if they are dizzy.1 in 4 people with falls risk who have benign paroxysmal positional vertigo do not report symptoms of dizzinessScreening for benign paroxysmal positional vertigo in all people who fall whether dizzy or not, is required to comprehensively identify and treat benign paroxysmal positional vertigoAll semicircular canals should be screened for benign paroxysmal positional vertigo as the incidence of multiple-canal involvement is high.

RESUMEN

The semicircular canals of the inner ear are involved in balance and velocity control. Being crucial to ensure efficient mobility, their morphology exhibits an evolutionary conservatism attributed to stabilizing selection. Release of selection in slow-moving animals has been argued to lead to morphological divergence and increased inter-individual variation. In its natural habitat, the house mouse Mus musculus moves in a tridimensional space where efficient balance is required. In contrast, laboratory mice in standard cages are severely restricted in their ability to move, which possibly reduces selection on the inner ear morphology. This effect was tested by comparing four groups of mice: several populations of wild mice trapped in commensal habitats in France; their second-generation laboratory offspring, to assess plastic effects related to breeding conditions; a standard laboratory strain (Swiss) that evolved for many generations in a regime of mobility reduction; and hybrids between wild offspring and Swiss mice. The morphology of the semicircular canals was quantified using a set of 3D landmarks and semi-landmarks analyzed using geometric morphometric protocols. Levels of inter-population, inter-individual (disparity) and intra-individual (asymmetry) variation were compared. All wild mice shared a similar inner ear morphology, in contrast to the important divergence of the Swiss strain. The release of selection in the laboratory strain obviously allowed for an important and rapid drift in the otherwise conserved structure. Shared traits between the inner ear of the lab strain and domestic pigs suggested a common response to mobility reduction in captivity. The lab-bred offspring of wild mice also differed from their wild relatives, suggesting plastic response related to maternal locomotory behavior, since inner ear morphology matures before birth in mammals. The signature observed in lab-bred wild mice and the lab strain was however not congruent, suggesting that plasticity did not participate to the divergence of the laboratory strain. However, contrary to the expectation, wild mice displayed slightly higher levels of inter-individual variation than laboratory mice, possibly due to the higher levels of genetic variance within and among wild populations compared to the lab strain. Differences in fluctuating asymmetry levels were detected, with the laboratory strain occasionally displaying higher asymmetry scores than its wild relatives. This suggests that there may indeed be a release of selection and/or a decrease in developmental stability in the laboratory strain.

Asunto(s)

RESUMEN

PURPOSE: The determinism of the sex is of most importance for reconstruction of the biological profile of deceased individuals. In this study, we aim to implement a technique to improve the accessibility of sex determination by the study of the bony labyrinth on cone-beam computed tomography (CBCT) and computed tomography (CT) scans. METHODS: CBCT and CT scans of temporal bones performed between 2014 and 2022 were collected with demographic information. The width of the lateral (LSCw), posterior (PSCw), and anterior semicircular canal (ASCw) was measured. The primary outcome was the diagnostic performance of the individual linear measures and the product of these measures. This analysis is supplemented by establishing thresholds using ROC curves. Inter-judge and intra-judge reliability evaluation was performed blinded in randomly selected exams. RESULTS: One hundred forty-one petrous bones were included for analysis of their imaging. The analysis of the PSCw, ASCw, and ASCw*PSCw for sex determination was associated with area under curves of 0.88 ± 0.11, 0.82 ± 0.14, and 0.84 ± 0.10 respectively and accuracies of 0.74 ± 0.13, 0.78 ± 0.11, and 0.79 ± 0.13 respectively. In ROC-curve analysis, a PSCw*ASCw product > 48.5 allows to determine a male sex with > 95% specificity and a sensitivity of 50.1%. A PSCw*ASCw product ≤ 43 allows to determine a female sex with 88% specificity and 64% sensitivity. Reproducibility analyses showed good to excellent intra-judge and inter-judge reproducibility for ASCw and PSCw. CONCLUSION: Linear measurement of the semicircular canals of the vestibule on CBCT or CT could provide easy-to-use sex determination of the majority of females and males with a good predictive value.

Asunto(s)

RESUMEN

OBJECTIVE: To search for any morphological variation contributing to aetiopathogenesis and the diagnosis of benign paroxysmal positional vertigo, we measured the sizes of the semicircular canals in patients with and without benign paroxysmal positional vertigo using multidetector computed tomography. METHODS: Cranial bone computed tomography images of 30 benign paroxysmal positional vertigo patients and 30 control patients were acquired with a 128-slice computed tomography scanner and a transverse plane with a thickness of 0.67 mm. The inner diameter, height and width of the canals were measured. RESULTS: The width of the anterior semicircular canals, and the width and height of the posterior semicircular canals of the affected ears in benign paroxysmal positional vertigo patients (n = 30) were significantly greater than in the control patients (n = 90; p = 0.001, p = 0.023, p = 0.003, respectively). CONCLUSION: In benign paroxysmal positional vertigo patients, the posterior and anterior semicircular canals are longer than those in people without benign paroxysmal positional vertigo. These morphological changes may contribute to elucidating the aetiopathogenesis and be used as a radiological sign for diagnosis of benign paroxysmal positional vertigo disease.

Asunto(s)

RESUMEN

OBJECTIVE To investigate the effect of individualized repositioning maneuver in the treatment of posterior semicircular canal benign paroxysmal positional vertigo(PC-BPPV)with limited neck movement.METHODS There were 163 patients with PC-BPPV admitted to the Department of Otolaryngology of Xiaolan People's Hospital of Zhongshan from January,2019 to July,2022 who were selected and divided into observation group(57 cases)and control group(106 cases)according to whether there was neck movement limitation or not.The control group was divided into control group 1(51 cases)and control group 2(55 cases)based on different reduction methods.The control group 1 were treated with modified Epley maneuver,and the observation group and the control group 2 were treated with individualized Epley maneuver.The cure rate and effective rate were compared among the three groups.The scores of vestibular symptom index(VSI),Berg balance scale(BBS)and the dimension scores of vertigo handicap inventory(DHI)were compared among the three groups before and after treatment.RESULTS There was no significant difference in the cure rate(84.37%vs.81.82%vs.80.70%)and effective rate(11.76%vs.10.91%vs.12.28%)among the three groups(P>0.05).After treatment,the scores of each dimension of VSI and DHI of PC-BPPV patients of the three groups decreased(P<0.01),and the scores of BBS increased(P<0.01),and there was no statistically significant difference in the scores of VSI(23.19±3.88 vs.23.70±4.01 vs.23.46±3.92),BBS(45.56±5.02 vs.45.14±4.98 vs.44.84±5.11)and each dimension of DHI among the three groups(P>0.05),respectively.CONCLUSION The individual Epley maneuver can effectively improve the vertigo status of patients with PC-BPPV with limited neck movement.

RESUMEN

OBJECTIVE: To outline the clinical picture of bilateral posterior canal benign paroxysmal positional vertigo. METHODS: A total of 573 patients with posterior canal benign paroxysmal positional vertigo were classified as having unilateral, or true or pseudo bilateral, posterior canal benign paroxysmal positional vertigo, and were treated with the Epley manoeuvre. Statistical significance was set at p < 0.05. RESULTS: Of the patients, 483 had unilateral and 90 (15.7 per cent) had bilateral presentation. Of the latter, 72 patients had pseudo bilateral posterior canal benign paroxysmal positional vertigo. Comparisons of site of involvement, male to female ratio and the incidence of associated problems in unilateral, and true and pseudo bilateral posterior canal benign paroxysmal positional vertigo did not reveal any statistically significant differences (p = 0.828, p = 0.200, p = 0.142). Comparisons of the number of manoeuvres required to provide symptom relief and the rate of recurrence were significant (p < 0.05). CONCLUSION: Identification of true and pseudo bilateral posterior canal benign paroxysmal positional vertigo is important given the differences in aetiology and treatment outcome. Treatment of patients with true bilateral posterior canal benign paroxysmal positional vertigo requires several therapeutic manoeuvre attempts, and patients should be warned about recurrence.

Asunto(s)

RESUMEN

Phosphatidylinositol 4 kinase-ß (PI4KB) plays critical roles in human genetic diseases. In zebrafish, Pi4kb is strongly expressed in hair cells (HCs), which are necessary for detecting sound vibrations, head movements, and water motion. However, the role of PI4KB in HC or semicircular canal development is unclear. Herein, we report that pi4kb morphants exhibit insensitivity to sound stimulation and abnormal morphological vestibular organs, including cilium loss in HCs of the cristae and semicircular canal malformation. As bone morphogenetic protein (BMP) signaling is associated with HC and semicircular canal development, we analyzed the expression of BMP-related genes; the phosphorylated Smad1/5/9 (p-Smad1/5/9) expression was markedly reduced in otic HCs. RNA-sequencing data indicated that the transcriptional levels of BMP membrane receptor 2 (bmpr2a and bmpr2b) and hes-related family of bHLH transcription factors with YRPW motif 1 (hey1), a direct downstream target gene of p-Smad, were significantly reduced in the pi4kb morphants, as verified using quantitative reverse transcription-polymerase chain reaction and in situ hybridization. Co-injection of hey1 mRNA and pi4kb morpholino notably recovered vestibular apparatus development, including the number and length of cilia in HCs of the cristae and semicircular canal formation. Collectively, these results suggest that Pi4kb is involved in vestibular apparatus development in zebrafish by regulating BMP membrane receptor 2 and p-Smad1/5/9 levels, thereby affecting the transcriptional activation of the target gene hey1. This study sheds light on the interaction between Pi4kb and the BMP-Hey1 signaling axis, which is critical for HC and semicircular canal formation.

Asunto(s)