[Show abstract][Hide abstract] ABSTRACT: Aetiological assessment of 71 probands whose clinical presentation suggested a genetic syndrome or auditory neuropathy.
Sanger sequencing was performed on DNA isolated from peripheral blood or lymphoblastoid cell lines. Genes were selected for sequencing based on each patient's clinical presentation and suspected diagnosis. Observed DNA sequence variations were assessed for pathogenicity by review of the scientific literature, and mutation and polymorphism databases, through the use of in silico tools including sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen), and according to the recommendations of the American College of Medical Genetics and Genomics for the interpretation of DNA sequence variations. Novel DNA sequence variations were sought in controls.
DNA sequencing of the coding and near-coding regions of genes relevant to each patient's clinical presentation revealed 37 sequence variations of known or uncertain pathogenicity in 9 genes from 25 patients. 14 novel sequence variations were discovered. Assessment of phenotypes revealed notable findings in 9 patients.
DNA sequencing in patients whose clinical presentation suggested a genetic syndrome or auditory neuropathy provided opportunities for aetiological assessment and more precise genetic counselling of patients and families. The failure to identify a genetic aetiology in many patients in this study highlights the extreme heterogeneity of genetic hearing loss, the incompleteness of current knowledge of aetiologies of hearing loss, and the limitations of conventional DNA sequencing strategies that evaluate only coding and near-coding segments of genes.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
[Show abstract][Hide abstract] ABSTRACT: Hearing loss is a common and complex condition that can occur at any age, can be inherited or acquired, and is associated with a remarkably wide array of etiologies. The diverse causes of hearing loss, combined with the highly variable and often overlapping presentations of different forms of hearing loss, challenge the ability of traditional clinical evaluations to arrive at an etiologic diagnosis for many deaf and hard-of-hearing individuals. However, identifying the etiology of a hearing loss may affect clinical management, improve prognostic accuracy, and refine genetic counseling and assessment of the likelihood of recurrence for relatives of deaf and hard-of-hearing individuals. Linguistic and cultural identities associated with being deaf or hard of hearing can complicate access to and the effectiveness of clinical care. These concerns can be minimized when genetic and other health-care services are provided in a linguistically and culturally sensitive manner. This guideline offers information about the frequency, causes, and presentations of hearing loss and suggests approaches to the clinical evaluation of deaf and hard-of-hearing individuals aimed at identifying an etiologic diagnosis and providing informative and effective patient education and genetic counseling.Genet Med advance online publication 20 March 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.2.
No preview · Article · Mar 2014 · Genetics in medicine: official journal of the American College of Medical Genetics
[Show abstract][Hide abstract] ABSTRACT: To review the presentation and management of improper electrode array placement, and to help guide clinical decision-making.
Retrospective case series.
Pediatric and adult cochlear implant patients managed from January 2001 to present whose electrode arrays were not placed properly within the cochlea or extended beyond the cochlea into the internal auditory canal or adjacent structures.
Four patients, three pediatric and one adult, were identified from over 824 cases (< 1%) managed over the study duration. All cases had normal cochlear anatomy. These cases were initially identified due to poor auditory skill development or absent behavioral responses following implantation, which prompted imaging. Two patients presented several years after surgery. Sites of improper placement included the eustachian tube, vestibule, internal carotid artery canal, and internal auditory canal (IAC). Intraoperative findings and management are reviewed.
Electrode array malpositioning is a rare, but serious and correctable complication in cochlear implant surgery. A multidisciplinary approach, including prompt audiologic evaluation and imaging, is important, particularly when benefit from the implant is limited or absent. Management of electrode arrays in the IAC may be more challenging. Laryngoscope, 2013
No preview · Article · Mar 2013 · The Laryngoscope
[Show abstract][Hide abstract] ABSTRACT: Chondroblastoma-like chondroma (CLC) of soft tissue is a rare benign neoplasm that usually involves the soft tissues of the hand. This report describes the first case of CLC of soft tissue arising in the base of the skull. A 33-year-old man was seen with a slow growing mass in the right parotid region of his face. The noncontrast computed tomographic scans showed an 8.5-cm mass with calcifications involving the right masticator space and extending through the bone into the middle cranial fossa. The radiologic differential diagnosis included osteosarcoma, leiomyosarcoma, chondrosarcoma, and giant cell tumor. During surgery, the large lateral skull base tumor appeared to involve the middle and infratemporal fossae and eroded the surrounding bone. Although the tumor was removed piecemeal, total excision was performed. On microscopic examination, the tumor displayed lobules of mature hyaline cartilage with numerous chondroblasts, coarse calcifications including chicken wire calcifications, and scattered osteoclasts. No atypia, mitoses, necrosis, or osteoid formation was seen. The tumor was diagnosed as chondroma with chondroblastoma features of the soft tissue. His postoperative clinical course was uneventful; however, after 7 months, he had a local recurrence identified on follow-up magnetic resonance imaging. He underwent repeat surgical excision of the tumor, which showed similar histology as the previous excision. This large skull based tumor eroding the bone, which clinically and radiologically mimicked a malignant process, was an unusual presentation of a benign cartilaginous neoplasm. Pathologists should be aware that CLC may occur in the base of the skull and this lesion should be differentiated from the other benign or malignant tumors arising in this area. These lesions have a potential for local recurrence; hence, a close follow-up is recommended.
No preview · Article · Jun 2012 · Annals of diagnostic pathology
[Show abstract][Hide abstract] ABSTRACT: Objective: Cochlear implant (CI) candidates undergo a preoperative workup including radiologic, audiologic, and neurologic testing to determine if they are candidates for implantation. A percentage of these patients are found to have aplasia/hypoplasia of the cochleovestibular nerve (CVN). Past literature has debated if this population of children benefit from CI.
Preview · Article · Sep 2011 · Otolaryngology Head and Neck Surgery
[Show abstract][Hide abstract] ABSTRACT: Selection of diagnostic tests for children with sensorineural hearing loss (SNHL) is influenced by clinical suspicion. Testing results reported in the literature are similarly biased. We evaluate the usefulness of a comprehensive diagnostic battery for each child.
Tertiary care university hospital.
A total of 270 children referred for severe to profound SNHL between January 2002 and June 2009.
Results of the following were reviewed: magnetic resonance imaging, computed tomography, renal ultrasound, electrocardiography, fluorescent treponemal antibody absorption test, connexin 26 sequencing, genetic consultation, and ophthalmologic consultation.
Diagnostic yield of each test was determined.
Each diagnostic test or consultation was completed by at least 95% of patients for whom it was ordered. Magnetic resonance imaging revealed abnormalities explaining SNHL in 24% of patients. Computed tomography showed inner ear anomalies in 18% of patients. Biallelic connexin 26 mutations were found in 15%. Renal ultrasound found anomalies in 4% of patients. Electrocardiography found 1% of patients with prolonged QT intervals. Fluorescent treponemal antibody absorption test result was positive in 0.5%. Genetic consultation found a genetic cause for hearing loss in 25%. Ophthalmologic consultation found abnormalities associated with hearing loss in 8%.
Diagnostic radiologic imaging is the highest yielding test for evaluating children with SNHL. Connexin 26 sequencing identifies a nearly nonoverlapping subset of children compared with imaging. Specialty consultations, particularly from a clinical geneticist, can improve diagnostic yield. Other tests, although of lower diagnostic yield for SNHL, can identify important diseases that significantly affect patient health.
Preview · Article · Feb 2011 · Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
[Show abstract][Hide abstract] ABSTRACT: To define the prevalence of inner ear anomalies in aural atresia patients and to recognize patterns of developmental anomalies in aural atresia patients.
Academic medical center.
Physical exam, audiometry, and temporal bone CT in selected patients.
Pediatric patients with aural atresia.
Prevalence of inner ear anomalies and coexisting facial paralysis or sensorineural hearing loss.
In this series of 118 patients with aural atresia, associated facial palsy was seen in 13%, whereas inner ear anomalies were present in 22%, including all patients with facial palsy. Interestingly, the inner ear anomalies often did not display a significant sensorineural hearing loss. Bilateral inner ear anomalies were frequently encountered despite unilateral atresia. Most anomalies involved the semicircular canals including several uncommon variants of posterior semicircular canal anatomy.
Inner ear anomalies are common in the presence of aural atresia, especially when there is concurrent congenital facial palsy. The presence of inner ear anomalies should be recognized as a common feature of craniofacial microsomia.
No preview · Article · Dec 2010 · Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
[Show abstract][Hide abstract] ABSTRACT: To examine the characteristics of pediatric cochlear implant channel malfunction preceding device failure.
: Retrospective review.
All pediatric patients who underwent cochlear implantation at a tertiary academic medical center were reviewed regarding device type, reason for replacement, time to replacement, and timing and pattern of channel faults in failed versus nonfailed devices.
Between 1993 and 2008, 264 pediatric cochlear implantations were performed. With an average 894-day follow-up, the replacement rate was 9.5% (25/264). Reasons for replacement were device failure (6.4%), medical/surgical failure (2.3%), and obsolescence (0.8%). Replacement rates were comparable among Advanced Bionics (13.3%), Cochlear Corporation (6.3%), and MED-EL (10.3%) devices. Fifty-two cochlear implants developed at least one channel fault, and 13 eventually progressed to failure requiring replacement. MED-EL devices comprised 12 of these 13 failures. At the 12-month follow-up interval, one, three, and five channel faults predicted 40%, 75%, and 100% probabilities of eventual electrode failure, respectively. Channels destined to fail demonstrated small, yet statistically significant, impedance elevations 12 months before failure and large elevations 3 months before failure.
Replacement of cochlear implants in pediatric patients is common and is due to device malfunction about one half of the time. Earlier initial channel fault, earlier subsequent channel faults, adjacent channel faults, and a greater total number of channel faults were associated with the need for replacement surgery. Elevations in a channel's impedance should raise the concern for an impending failure. These predictors can help the cochlear implant team when considering surgery to replace the device.