HRCT Analysis Of Inner Ear Malformation And Deafness Gene Mutations In Chinese Pedigrees With SNHL

BackgroundProfound congenital hearing impairment is the most frequently occurring birth defect, with an estimated incidence of approximately 1-3:1000 births in the US.Deafness has many recognized genetic and environmental causes,many previous studies have suggested that about 50%of profound deafness is genetic in etiology,with the remainder of cases attributed to environmental causes such as congenital infection,fetal ototoxic drug exposure and trauma.The advance of Human Genome has brought along the epoch of molecular medicine, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment.The American College of Medical Genetics has recommended that all infants with confirmed hearing loss,who are identified in newborn screening programs, should be referred to a geneticist for clinical evaluation,the performance of indicated genetic tests,and counseling.Previous reports have described that mutations in GJB2, or connexin 26,encoding gap junction beta 2 protein are responsible for the commonest form of non-syndromic recessive deafness in many populations.A specific genetic diagnosis can sometimes be of great clinical importance,as in the case of the mitochondrial A1555G mutation which causes gene carriers to be exquisitely sensitive to the ototoxic effects of amino-glycosides. Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling, it is expected that new diagnostic techniques could be adopted to prevent part of the environmental and hereditary deafness by molecular genetic tests and genetic counseling.In addition,genetics can provide empowering knowledge to many deaf couples to know whether their children will be hearing or deaf even before they are conceived.Inner ear malformations may be associated with sensorineural hearing loss(SNHL), imaging examination plays a crucial role in the diagnosis of inner ear malformations, and so in the assessment of SNHL,detailed images with high resolution are mandatory for the demonstration of small pathological processes.With the development of HRCT in the 1980s,HRCT became the first line recommended method of choice in the evaluation and management of hearing impairment,malformations and destructive processes in the middle and inner ear.Because of the detailed display of soft tissue and bony structures,small bony pathologies can be well visualized.With special software, the acquired data allowed the reconstruction of three-dimensional images of missing sections,with this method,loss of information was compensated for by a lower radiation dose.Identification of obvious morphogenetic malformations is not difficult. However,the recognition of these less severe anomalies is dependent on the clinical experience of the clinician and nearly one-third of less severe inner ear anomalies may be missed.Children affected by SNHL before 6 years of age may leads to deficits in speaking and communication abilities,which,in turn,negatively affect the child's social and educational development.Importance of the early diagnosis and intervention of hearing loss has been increasingly valued.Cochlear implant is considered an effective procedure to treat patients with severe(between 70 and 90 dB) to profound(＞90dB) bilateral SNHL,and that have not benefited from conventional sound amplification hearing aids.In the last years,cochlear implantation has gained widespread acceptance in the Chinese profoundly deaf patients.Evaluation by imaging methods is critical in the preoperative care of cochlear implant(CI) surgery,providing safety to surgeons when indicating and performing this procedure.As demands for Cochlear implant increase,surgeons should be aware of what key points they have to check before implanting patients.HRCT has been of high value in clinical application of analysis of each inner ear malformations and help to guide proper treatment of each patient. However,there has been little written about the correlation of specific inner ear malformations with their clinical presentation and management.This paper is composed of three parts as follows:The aim of the first study was to analyze the HRCT imaging features in patients with SNHL and discussed the clinical values of HRCT in diagnosis of congenital inner ear malformations and preoperative evaluation for cochlear implantation by correlating preoperative radiological signs with surgical findings.In the second study we screened GJB2,PDS gene mutations in patients of SNHL using direct sequencing analysis,for the purpose of accumulating the experience and samples for the new technique of the detection of gene mutation and collection basic information for the clinical application of genetic diagnosis and genetic counseling of SNHL.The popurse of the third study was to evaluate the effect of semicircular canal occlusion on hearing in the treatment of labyrinthine fistula caused by cholesteatoma.Part one HRCT Analysis and Cochlear Implantation in Patients with Inner Ear MalformationObjective:1.To investigate the HRCT findings in children with SNHL and discuss it's clinical values in the diagnosis of congenital inner ear malformations and preoperative evaluation for cochlear implantation.2.Using standardized measurements of central bony island width within the LSCC to investigate the lateral semicircular canal(LSCC) anomalies and the coexistence of other inner ear anomalies on HRCT imaging that occur in association with LVAS.3.To analyze the surgical indications,prevention of complication and surgical difficulty of cochlear implant in patients with congenital inner ear malformations.Methods: 1.One hundred and twelve children with SNHL performed HRCT scan,the digitally stored temporal bone multi-slice spiral CT imaging of the inner ear structures were reviewed and the 3-dimensional reconstructions and multiplanar reformation(MPR) were performed using the volume-rendering technique(VRT) on the workstation.2.The measurements of the central bony island width within the LSCC on axial imaging at the level of LSCC from the children with LVAS were performed on the workstation.3.The cochlear implantations were performed in 86cases of our patients,routine transmastoid facial recess approach was performed in these Cases.The medical records of all patients undergoing CI surgery were studied.Results:1.Among 112 patients,78 patients were normal and 34 patients(68ears) were congenital inner ear malformations.The malformations were as follows:Michel deformity one case(two ears Fig.2),incomplete partition typesⅠone case(IP-Ⅰ,two ears,accompanyied by vestibule lateral semicircular canal dysplasia),incomplete partition typesⅡ3 cases(IP-Ⅱ,Mondini deformity,6 ears,accompanied by dilation of lateral semicircular canal and vestibule,enlarged vestibular aqueduct),vestibule and lateral semicircular canal dysplasia 3cases(6ears),isolated semicircular canal abnormality 4 cases(8ears), narrow internal auditory canal one case(two ears),X-linked inherited deafness one case(two ears),enlarged vestibular aqueduct 20 cases(39ears).2.The axial,MPR and VRT reconstruction images can display the site and degree in the ears with inner ear malformations.The VRT reconstruction images can display the malformations of inner ear three-dimensionally and intuitively.3.In all cases the diagnosis of inner ear malformation was made by CT imaging. Combined deformities were found in all of the patients with cochlear or vestibule dysplasia in our sieries,and the single structure abnormalities were found only in isolated semicircular canal dysplasia or isolated enlarged vestibular aqueduct.4.The measurements of the central bony island width within the LSCC showed:A small bony island of the LSCC(＜3mm in diameter) appears highly typical in patients with LVAS.Coexistent inner ear anomalies are common in LVAS. 5.Eighty-six patients received a cochlear implant.The cochlear implantations were performed in 8 patients with the malformation of inner ear.In this series,there were 6cases of large vestibular aqueduct syndrome(LVAS),1 cases of incomplete partition typesⅠ,and 1 cases of Mondini malformation.Conclusion:1.HRCT allows a comprehensively assessing various congenital inner ear malformations through high quality MPR and VRT reconstructions.It is very useful to the cochlear implantation.2.Measurement of the inner ear structures,in conjunction with visual inspection of CT images,will increase recognition of subtle inner ear abnormalities.3.For the patients with inner ear malformations,it is important to accurately assess the extent of abnormalities in the inner ear and accompanied malformations before operation,and to evaluate the full extent of difficulties of the operation in order to minimize the risk of CSF leakage.4.Inner ear malformations can not be a contraindication to implantationfor cochlear implantation in children,but it is important to be aware of the various aspects of the surgical management and to attempt to minimize the risks of complications.Cochlear implant is potentially a good functional solution for patients suffering from large vestibular aqueduct syndrome.Part two Detection of Heredity Deafness Gene Mutations in Chinese Family Suffered from SNHLObjective:To identify the prevalence of deafness related gene mutations in patients with SNHL, for the purpose of accumulating the experience and samples for the new technique of the detection of gene mutation and collection basic information for the clinical application of genetic diagnosis and genetic counseling of SNHL. Methods:Two Chinese families suffered from SNHL accompanied by diabetes mellitus and three Chinese families suffered from SNHL associated with enlarged vestibular aqueduct(EVA) were collected.Genomic DNA was extracted from peripheral blood cells of all patients and the others of their pedigree.All the coding exons and their flanking sequences of the testing gene were amplified by polymerase chain reaction (PCR).The products were analyzed totest the PDS gene,GJB2 gene and Mt 3243 gene mutations in these families.Results:There are no GJB2 and Mt 3243 gene mutations found in the two Chinese family suffered from SNHL accompanied by diabetes mellitus.SLC26A4 gene mutation was found in two of the three Chinese families suffered from SNHL associated with enlarged vestibular aqueduct.Conclusion:The mutations of GJB2 are not likely to be the cause of SNHL accompanied by diabetes mellitus in our siries.More studies are needed.SLC26A4 mutations were found in the family with EVA.Genetic test for this mutation is necessary for prenatal diagnosis of these two families,and genetic testing can provide efficient information about hearing condition of their offsprings.Part three Lateral Semicircular Canal Plugging for Treatment of Labyrinthine Fistula Caused by CholesteatomaObjective:To evaluate the effect of semicircular canal occlusion on hearing in the treatment of labyrinthine fistula caused by cholesteatomaMethods:Retrospective study based on 16 cases of labyrinthine fistula caused by cholesteatoma. The preoperative symptoms,incidence of labyrinthine fistula,type of surgery and preoperative and postoperative hearing function and intraoperative findings were analyzed.Preoperative high resolution computed tomography(HRCT) scans and the MPR reconstruction were performed on all patients,Results:1.All patients were detected to be with labyrinthine fistula in preoperative HRCT imaging.During the operation the lateral semicircular canal was found in all of the cases.2.During surgery the matrix over the fistula was removed in all cases.Occlusion of the lateral semicircular canal for the treatment of labyrinthine fistula was performed in all cases.Postoperative change of bone conduction threshold was not significantly different compared with preoperative bone conduction threshold(P＜0.05).3.The patients were followed up for an average time of 15 months,dizziness disappeared completely in all cases and the preservation of the bone conduction threshold was obtained when semicircular canal occlusion surgical technique is used.Conclusion:1.Preoperative HRCT scan and MPR reconstruction technique is useful in diagnosis of labyrinthine fistula.but it s limitations should also be recognized.The verification of a labyrinthine fistula can be definitively established only at the time of surgery.2.The current study confirmed that careful manipulation of the labyrinthine fistula is safe to preserve hearing functions for these patients.3.Hearing preservation can be obtained when semicircular canal occlusion surgical technique is used.