Discovery of sensorineural hearing loss and ossicle deformity in a Chinese Li nationality family with spondyloepiphyseal dysplasia congenita caused by p.G504S mutation of COL2A1

Background Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant chondrodysplasia characterized by disproportionate short stature, abnormal epiphyses, and flattened vertebral bodies. COL2A1 has been confirmed as the pathogenic gene. Hearing loss represents an infrequent manifestation for 25–30% of patients with SEDC. The characteristics of the hearing impairment were rarely documented. Methods Audiological, ophthalmic, imaging examinations were conducted on the family members. The whole exome sequencing (WES) was performed to detect the candidate gene, and the Sanger sequencing was used to confirm the causative variation. Results COL2A1 c.1510G>A (p.G504S), a hot spot variation, was identified as the disease-causing mutation of the Chinese Li nationality family with SEDC. This variation was co-segregated with the SEDC phenotype in the family and was absent in the 1000 Genomes Project, ESP and ExAC. Clinically, several manifestations were first demonstrated in SEDC patients caused by p.G504S, including sensorineural hearing loss, auditory ossicles deformity, retinal detachment, sacrum cracked and elbow and wrist joints deformity. Other classical SEDC manifestations such as bones and joints pain, midfacial dysplasia, disproportionate short stature, spinal deformity, thoracocyllosis, coxa arthropathy, myopia and waddling gait were also showed in the family patients. Conclusion We first identified the mutation p.G504S in COL2A1 gene as the pathogenesis in a Chinese Li nationality family and reported the correlation between p.G504S and atypical clinical phenotypes including sensorineural hearing loss, auditory ossicles deformity, retinal detachment, sacrum cracked and elbow and wrist joints deformity. Our findings would extend the phenotypic spectrum of SEDC and deepen clinicians' understanding of genotype–phenotype correlation of the disease.

The Biophysical Function of the Human Inner Ear

The ear transforms soft mechanical vibration of air particles into electrical signals, which reach the appropriate part of the cerebral cortex for processing by means of auditory nerves. The process of the hearing is next: the eardrum vibrates from the sound waves; auditory ossicles amplify the stimulus; in an oval window, the vibration is transmitted to the fluid space of the inner ear; iIt vibrates the basilar membrane; what is pressed against the membrane tectoria; the stereocilliums of the hair cell bend, ion channels open; hair cell depolarizes; stimulus is dissipated in cerebrospinal fluid VIII (vestibulocochlearis); temporal lobe primary auditory cortex (Brodman 41, 42); association pathways: speech comprehension (Wernicke area). For the rising prevalence of psychoses (mental disorders) in the last decades among towns­people, these stimuli – as compared to the abandoned environment – and the adaptation to them may also play a definite role. The man, therefore, enjoying worths and conveniences of the civilization has to size every opportunity to get into the open, to compensate the monotony of the external stimuli, in a word, to grant his organism those stimuli which he claims as a biological creature. This human demand – it seems – is such a great physiological need that our organism cannot be without even in the evening. At least this turns out according to the researches relating sleep and dreaming.

The Biophysical Function of the Human Eardrum

The hearing analyzer consists of two main systems: the peripheral hearing system, formed of the outer ear, the middle ear and the inner ear and the central hearing system, which contains the nervous pathways which ensure the transmission of the nervous influx and the hearing area where the information is analyzed and the hearing sensation is generated. The peripheral hearing system achieves the functions of transmission of the sound vibration, the analysis of the acoustic signal and the transformation of the acoustic signal in nervous inflow and the generation of the nervous response. The human hearing is characteristics: 1. The eardrum vibrates from the sound waves; 2. Auditory ossicles amplify the stimulus; 3. In an oval window, the vibration is transmitted to the fluid space of the inner ear; 4. It vibrates the basilar membrane; 5. What is pressed against the membrane tectoria; 6. The stereocilliums of the hair cell bend, ion channels open; 7. Hair cell depolarizes; 8. Stimulus is dissipated in cerebrospinal fluid VIII (vestibulo¬cochlearis); 9. Temporal lobe primary auditory cortex (Brodman 41, 42); 10. Association pathways: speech comprehension (Wernicke area).

Treatment choice for repair of sound-conducting apparatus with isolated ossicular anomalies

Over the last decades, attention to the study of the possibilities of pediatric otorhinolaryngology has increased. The constantly evolving technologies in reconstructive surgery and advances in the field of anesthetic management have made it possible to carry out the necessary surgical interventions at the earliest possible time. Even such traditionally complex areas like treatment of isolated middle ear abnormalities receive more and more opportunities for successful development. In order to achieve maximal results of hearing in isolated ossicular abnormalities, various approaches to their reconstruction are used. In our work, we aimed to find out which of the two most topical technical solutions is optimal in terms of functional results’ achievement. To do this, we analyzed two independent groups of patients in whom different approaches to the repair of the sound conduction was applied. On the basis of the study, it can be argued that attempts to preserve a deformed, but movable chain of the auditory ossicles, that is, performing type 1 tympanoplasty with an intact stapes with anomalies in the development of auditory ossicles did not prove their feasibility. Performing surgery using a simpler technique, namely with the removal of deformed ossicles and the use of partial titanium prostheses, allows you to achieve the best anatomical and functional results.

A new method to determine the optimal orientation of Slim Modiolar cochlear implant electrode array insertion

Our goal was to determine the optimal orientation of insertion of the Slim Modiolar electrode and develop an easy-to-use method to aid implantation surgery. In some instances, the electrode arrays cannot be inserted in their full length. This can lead to buckling, interscalar dislocation or tip fold-over. In our opinion, one of the possible reasons of tip fold-over is unfavourable orientation of the electrode array. Our goal was to determine the optimal orientation of the Slim Modiolar electrode array relative to clear surgical landmarks and present our method in one specified case. For the measurement, we used the preoperative CT scan of one of our cochlear implant patients. These images were processed by an open source and free image visualization software: 3D Slicer. In the first step we marked the tip of the incus short process and then created the cochlear view. On this view we drew two straight lines: the first line represented the insertion guide of the cochlear implant and the second line was the orientation marker (winglet). We determined the angle enclosed by winglet and the line between the tip of the incus short process and the cross-section of previously created two lines. For the calculation we used a self-made python code. The result of our algorithm for the angle was 46.6055°. To validate this result, we segmented, from the CT scan, the auditory ossicles and the membranaceous labyrinth. From this segmentation we generated a 3D reconstruction. On the 3D view, we can see the position of the previous lines relative to the anatomical structures. After this we rotated the 3D model together with the lines so that the insertion guide forms a dot. In this view, the angle was measured with ImageJ and the result was 46.599°. We found that our method is easy, fast, and time-efficient. The surgery can be planned individually for each patient, based on their routine preoperative CT scan of the temporal bone, and the implantation procedure can be made safer. In the future we plan to use this method for all cochlear implantation surgeries, where the Slim Modiolar electrode is used.