Search Results (10)

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27^−/− mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation. Full article

Individuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspects of hearing loss, we collected information on hearing status from 21 individuals with KS1 and found that individuals have both sensorineural and conductive hearing loss, with the average age of presentation being 7 years. Our data suggest that while ear infections and structural abnormalities contribute to the observed hearing loss, these factors do not explain all loss. Using a KS1 mouse model, we found hearing abnormalities from hearing onset, as indicated by auditory brainstem response measurements. In contrast to mouse and human data for CHARGE syndrome, a disorder possessing overlapping clinical features with KS and a well-known cause of hearing loss and structural inner ear abnormalities, there are no apparent structural abnormalities of the cochlea in KS1 mice. The KS1 mice also display diminished distortion product otoacoustic emission levels, which suggests outer hair cell dysfunction. Combining these findings, our data suggests that KMT2D dysfunction causes sensorineural hearing loss compounded with external factors, such as infection. Full article

Tinnitus is the perception of abnormal sounds in the ears or head without external auditory stimulation. While classical test theory is often used in tinnitus questionnaire development, it has limitations in assessing item characteristics. Item response theory (IRT) offers more precise individual ability estimations and identifies key and less important items, making it superior for reliable measurement tools. This study investigated the suitability of the Korean version of the Tinnitus Handicap Inventory (K-THI) as a patient-reported outcome measure (PROM) for clinical trials. Using Rasch analysis based on IRT, we evaluated K-THI’s measurement of tinnitus-related disability in 545 patients (40.4% men, 59.6% women). Five items (2, 7, 8, 19, and 24) did not fit the Rasch model, yet a unidimensional scale and good fit for person and item data emerged (person: 0.89; item: 0.98). The three-point rating scale in K-THI proved suitable. IRT allowed precise evaluation of K-THI’s properties, vital for reliable PROMs in patient-centered care. Our findings highlight IRT’s role in questionnaire development, contributing to the advancement of PROMs. Full article

Conductive hearing losses are typically present in disorders of the external/middle ear. However, there is a rare group of inner ear conditions called third windows that can also generate a conductive hearing loss. This is due to an abnormal connection between the middle and the inner ear or between the inner ear and the cranial cavity. X-linked gusher disorder is an extremely rare congenital inner ear dysplastic syndrome with an abnormal connection due to a characteristic incomplete cochlear partition type III and an incomplete internal auditory meatus fundus. The disorder is inherited in an X-linked fashion due to the mutation of the POU3F4 gene. We present two siblings diagnosed with the condition and their long-term follow-ups. They both presented audiovestibular symptoms and showed progressive mixed losses and bilateral vestibular weakness. They were treated with cochlear implant, digital amplification and with vestibular rehabilitation. Significant others around them were involved in their journey with the medical team, and in both, a very favourable outcome was achieved. This is the first time that we have reported evolving audiovestibular function with vestibular quantification in X-linked gusher disorder and emphasize on the multidisciplinary holistic approach to manage these children effectively. Full article

Tympanosclerosis is an abnormal disorder of the middle ear or only the eardrum (i.e., myringosclerosis) in which there are calcium deposits. Normally, it is caused by recurrent middle ear infections. In this work, a 3D finite element model of the ear was developed, simulating different cases of tympanosclerosis. Through this model, the magnitude and the phase angle of the umbo and stapes displacement were obtained. The middle ear sound transfer function was determined for a stimulus of 80, 90 and 100 dB SPL, in a frequency range between 100 Hz and 10 kHz, applied on the outer surface of the eardrum in the external auditory canal. Depending on the tympanosclerosis affected area, the main conclusion is that worse results (leading to hearing loss) occur when all of the ossicular chain is affected. Full article

Herpes zoster oticus (HZO) is characterized by otalgia and erythematous vesicles in the auricle or external auditory canal. Ramsay Hunt syndrome (RHS) can be diagnosed when facial nerve palsy is accompanied by these symptoms of HZO, and in this case, audio-vestibular symptoms such as hearing loss or dizziness often develop. Recently, 3D-fluid-attenuated inversion recovery sequence (3D-FLAIR) magnetic resonance imaging (MRI) has been introduced in order to evaluate the inner ear structure pathology. The purpose of this study was to investigate the audio-vestibular characteristics in correlation with temporal bone MRI findings in HZO patients. From September 2018 to June 2022, 18 patients with HZO participated in the study. Thirteen patients (77%) showed high-signal intensity in the inner ear structures in 4 h post-contrast 3D-FLAIR images. In a bithermal caloric test, the lateral semicircular canal showed high signal intensity in 4 h post-contrast 3D-FLAIR images in 75% of patients with abnormal canal paresis. While the cochlea showed high signal intensity in 4 h post-contrast 3D-FLAIR images in 75% of patients with hearing loss, the vestibulo-cochlear nerve showed enhancement in post-contrast T1-weighted images in only 33% of patients with hearing loss. The present study demonstrates that audio-vestibular deficits are well-correlated with increased signal intensity of the inner ear endorgans in 4 h post contrast 3D-FLAIR MRI. Full article

Otitis is an ear inflammation characterized by an accumulation of polluted fluids in the ear, inflating the drum, causing ear pain, and draining the mucous membrane (pus) into the ear canal if the drum is perforated. Swimmer’s otitis, also known as acute external otitis, is a medical condition that frequently affects competitive swimmers. The risk factor analysis study was based on data obtained between May 2018 and May 2019 from four public swimming pools in Patras, Achaia. A checklist was created to evaluate the pools’ operational conditions, and it included information on the pools’ sanitation as well as swimming pool hygiene guidelines. In addition, a questionnaire was devised to collect data on pool swimmers’ use of the pools. Microbiological testing of the pool water was done ahead of time, and data on external otitis cases from hospitals was gathered. Based on this information, a risk factor analysis was conducted. Gender, weight, and age do not appear to have an impact on the number of otitis media cases that occur because of swimming in the pools. There is also no statistically significant link between episodes and the frequency of otitis events in locker rooms, restrooms, or swimming pools. The frequency with which swimmers utilize the pool, rather than the pool’s microbial burden, is the most significant determinant in otitis episodes. Furthermore, there is no statistically significant link between chlorine odor and otitis episodes. Additionally, several abnormalities in the ear or the child’s history do not appear to affect otitis episodes. More research is needed to determine whether infections are linked to microbial load or if other factors are responsible for the emergence of waterborne infections. Full article

Itch (pruritus) is a common chronic condition with a lifetime prevalence of over 20%. The mechanisms underlying itch are poorly understood, and its therapy is difficult. There is recent evidence that following nerve injury or inflammation, intercellular communications in sensory ganglia are augmented, which may lead to abnormal neuronal activity, and hence to pain, but there is no information whether such changes take place in an itch model. We studied changes in neurons and satellite glial cells (SGCs) in trigeminal ganglia in an itch model in mice using repeated applications of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the external ear over a period of 11 days. Treated mice showed augmented scratching behavior as compared with controls during the application period and for several days afterwards. Immunostaining for the activation marker glial fibrillary acidic protein in SGCs was greater by about 35% after TNCB application, and gap junction-mediated coupling between neurons increased from about 2% to 13%. The injection of gap junction blockers reduced scratching behavior, suggesting that gap junctions contribute to itch. Calcium imaging studies showed increased responses of SGCs to the pain (and presumed itch) mediator ATP. We conclude that changes in both neurons and SGCs in sensory ganglia may play a role in itch. Full article

Labyrinthine aplasia, microtia, and microdontia (LAMM) is an autosomal recessive condition causing profound congenital deafness, complete absence of inner ear structures (usually Michel’s aplasia), microtia (usually type 1) and microdontia. To date, several families have been described with this condition and a number of mutations has been reported. We report on eight further cases of LAMM syndrome including three novel mutations, c. 173T>C p.L58P; c. 284G>A p.(Arg95Gln) and c.325_327delinsA p.(Glu109Thrfs*18). Congenital deafness was the primary presenting feature in all affected individuals and consanguinity in all but two families. We compare the features in our patients to those previously reported in LAMM, and describe a milder, asymmetrical phenotype associated with FGF3 mutations. Full article

This paper describes a rare case of fibrous dysplasia with cystic degeneration in the mandibular condyle. Diagnostic and therapeutic considerations are discussed. A 40-year old woman presented with pain near the region of her right ear. Physical and radiographic examination showed no abnormalities besides the presence of a mixed radiopaque/radiolucent expansive lesion of the right condyle. Pathologic examination showed high bone-turnover with bone formation. Bone scintigraphy showed a monostotic active fibrous lesion in the right part of the mandible. Bisphosphonate treatment did not sufficiently treat the patient’s symptoms and physiotherapy to treat craniomandibular dysfunction as a factor in the pain was also unsuccessful. The patient later developed an acute external otitis due to a narrowed outer ear canal and had to be admitted to the hospital for treatment with intravenous antibiotics. Approximately two years after first presentation, resection of the affected bone (condylectomy) and reconstruction with a custom total joint prosthesis was indicated due to repeated functional deficits with considerable morbidity. Pathologic examination of the resected mandibular condyle showed increased bone formation including formation of neocortex and some cystic formation. This was diagnosed as fibrous dysplasia with cystic degeneration. Approximately two years after surgery, the patient functioned well. Full article