Progressive Sensorineural Hearing Loss Research Articles

Improvement of Fabry disease pain with calcium gluconate infusions given at time of agalsidase beta therapy

Fabry disease (FD) is a lysosomal storage disorder (LSD) that involves the cochleovestibular system. Tinnitus and progressive sensorineural hearing loss are frequent complains. A stabilization of hearing function has been reported with enzyme replacement therapy (ERT). This study aims to characterize the inner ear involvement, identify factors associated to hearing loss and evaluate the effect of ERT on the hearing function of FD patients.We reviewed the clinical records of patients with confirmed diagnosis of FD followed in a Reference Centre on LSD in the North of Portugal.We included a total of 122 patients with a mean age of 47.1 ± 17.6 years and 48.3% males. Hearing loss was reported by 26.2% of the patients and 23.0% mentioned tinnitus. Pure tone audiometry revealed sensorineural hearing loss in 36.9% of the cases. FD patients presented worse age-adjusted hearing thresholds in all analysed frequencies compared to the normal population (p = .001). Patients with hearing loss presented a significantly higher value of microalbuminuria (p = .001) and a higher frequency of acroparesthesias (p = .032). Patients presented a comparable hearing level one year after starting ERT (p = .384).In FD, hearing loss is common and age-matched hearing thresholds by frequency are worse than in the general population. Hearing loss was associated to the presence of acroparesthesias and higher values of microalbuminuria. Hearing loss stabilized in patients under ERT. A careful cochleo-vestibular evaluation should be part of the clinical assessment of FD.

Vestibular Involvement in Patients With Otitis Media With Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Otitis media (OM) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is a novel concept of ear disease that is characterized by progressive mixed or sensorineural hearing loss with occasional systemic involvement. Considering the accumulating knowledge about the characteristics of and treatment for auditory dysfunction in OMAAV, the objective of this study was to investigate the vestibular function and symptoms of patients with OMAAV. Retrospective chart review. University hospital. Thirty-one OMAAV patients met criteria proposed by the OMAAV study group in Japan. Clinical characteristics and vestibular tests. Eleven of 31 OMAAV patients had vestibular symptoms; 3 patients had acute vertigo attack with sudden hearing loss and 8 patients had chronic dizziness. Episodic vertigo was not seen in any of the patients. Three patients who received a less intensive therapy without immunosuppressive agents developed intractable persistent dizziness. All symptomatic patients and six of the nine OMAAV patients without vestibular symptoms showed unilateral or bilateral caloric weakness; therefore, vestibular involvement was present in 84% of OMAAV patients. Gain of vestibulo-ocular reflex was reduced in symptomatic patients. The eye-tracking test and optokinetic nystagmus revealed no evidence of central dysfunction. Vestibular dysfunction was seen in 84% of OMAAV patients. One-third of OMAAV patients showed vestibular symptoms such as acute vertigo attack or chronic dizziness, which are of peripheral origin. One-third of the symptomatic patients developed intractable dizziness. Initial intensive treatment by combination therapy with steroid and immunosuppressive agents may be essential for preventing the development of intractable dizziness.

Krukenberg Tumor with Leptomeningeal Carcinomatosis Misdiagnosed as Acoustic Neuroma

Objective: Leptomeningeal carcinomatosis (LMS) is defined as the diffuse infiltration of the leptomeninges and subarachnoid space by malignant cells metastasizing from systemic cancer. Patients usually have a known underlying malignancy, but primary presentation can be with symptoms of meningeal involvement. We describe a rare case of Krukenberg tumor with LMS initially presented as bilateral progressive sensorineural hearing loss, which was misdiagnosed as acoustic neuroma. Patient: A 50 year old man with a history of cervical cancer was referred to the Ear Nose and Throat (ENT) clinic because of progressive hearing loss, tinnitus, dizziness and blurred vision for 5 months. Results: A CT scan of the abdomen and pelvis showed a right adnexal mass, suspicious for an ovarian neoplasm. The patient underwent surgical resection of her pelvic mass. Surgical pathology revealed poorly differentiated adenocarcinoma with scattered signet ring cells, favorable with metastatic gastric adenocarcinoma. Magnetic resonance imaging revealed abnormal leptomeningeal enhancement. A lumbar puncture was performed, the CSF analysis showed elevated protein and positive for signet malignant cells. Conclusion: Our case highlights the importance of the development of new diagnostic tools and treatment regimens for LMC.

Primary Solitary Intralabyrinthine Schwannoma: A Report of 7 Cases and a Review of the Literature

Intralabyrinthine schwannomas (ILSs) are uncommon benign tumors that originate in the Schwann cell sheath of the intralabyrinthine distal branches of the vestibulocochlear nerve. They have no initial involvement in the internal auditory canal, although that might develop later. These lesions can arise inside the cochlea, originate in the vestibule or, in rare cases, develop in the semicircular canals. From these sites, spread might take place via the anatomic connections between the perilymphatic spaces in the scala vestibuli and the anterior vestibule. Thus, ILSs centered in the cochlea might involve the vestibule, and those originating in the vestibular end organs would reach the cochlea. Presenting signs and symptoms include a progressive or sudden sensorineural hearing loss (which occurs in more than 95% of patients), as well as tinnitus and vertigo. Magnetic resonance imaging characteristics include sharp circumscription and hypointensity on thin, heavily T2-weighted 3D images and strong enhancement after gadolinium administration on T1-weighted images. We describe a series of 7 cases of primary ILS that were managed at two of our institutions. We also discuss the need for a comprehensive otoneurologic evaluation that encompasses the functional derangement and the tumor location as delineated by MRI, and we describe the treatment options.

Syndrome d’Alport : néphropathie héréditaire associée à des mutations dans les gènes codant les chaînes de collagène de type IV

Alport syndrome is an inherited disorder characterized by the association of a progressive haematuric nephropathy with ultrastructural abnormalities of the glomerular basement membranes, a progressive sensorineural hearing loss and sometimes ocular involvement. Its incidence is less than 1 per 5000 individuals and the disease is the cause of about 2% of end stage renal disease in Europe and the United States. Alport syndrome is clinically and genetically heterogeneous. It is related to mutations in the genes encoding one of three chains, α3, α4 α5 of type IV collagen, the main component of basement membranes, expressed in the glomerular basement membrane. COL4A5 mutations are associated with X-linked Alport syndrome, which represents 80 to 85% of cases and is more severe in boys than in girls. Mutations in COL4A3 or COL4A4 are associated with autosomal Alport syndrome. The expression of collagen chains in skin and kidney basement membranes allows for the diagnosis and characterization of the mode of transmission in most patients. It is necessary to diagnose this syndrome because its family involvement, its severity, and the importance of genetic counseling. Angiotensin blockers are increasingly prescribed in proteinuric patients. Prospective studies are needed to assess the effectiveness of these treatments on proteinuria and progression of kidney failure, and to specify indications. Animal studies have shown the potential value of different molecules (protease inhibitors, chemokine receptor blockers, transforming growth factor-β1 inhibitors, hydroxy-methyl-coenzyme A reductase inhibitors, bone morphogenetic protein-7 inhibitors), hematopoietic stem cells, and of a anti-micro-RNA.

Discovery of CDH23 as a Significant Contributor to Progressive Postlingual Sensorineural Hearing Loss in Koreans.

CDH23 mutations have mostly been associated with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic or nonsyndromic SNHL (DFNB12). Herein, we demonstrate the contribution of CDH23 mutations to postlingual nonsyndromic SNHL (NS-SNHL). We screened 32 Korean adult probands with postlingual NS-SNHL sporadically or in autosomal recessive fashion using targeted panel or whole exome sequencing. We identified four (12.5%, 4/32) potential postlingual DFNB12 families that segregated the recessive CDH23 variants, qualifying for our criteria along with rapidly progressive SNHL. Three of the four families carried one definite pathogenic CDH23 variant previously known as the prelingual DFNB12 variant in a trans configuration with rare CDH23 variants. To determine the contribution of rare CDH23 variants to the postlingual NS-SNHL, we checked the minor allele frequency (MAF) of CDH23 variants detected from our postlingual NS-SNHL cohort and prelingual NS-SNHL cohort, among the 2040 normal control chromosomes. The allele frequency of these CDH23 variants in our postlingual cohort was 12.5%, which was significantly higher than that of the 2040 control chromosomes (5.53%), confirming the contribution of these rare CDH23 variants to postlingual NS-SNHL. Furthermore, MAF of rare CDH23 variants from the postlingual NS-SNHL group was significantly higher than that from the prelingual NS-SNHL group. This study demonstrates an important contribution of CDH23 mutations to poslingual NS-SNHL and shows that the phenotypic spectrum of DFNB12 can be broadened even into the presbycusis, depending on the pathogenic potential of variants. We also propose that pathogenic potential of CDH23 variants and the clinical fate of DFNB12 may be predicted by MAF.

Clinical Reasoning: A complicated case of MELAS

A 48-year-old right-hand-dominant woman presented to the emergency department with sudden onset of visual loss of her left visual field. She had a complicated medical history—end-stage renal disease requiring renal transplant 6 years prior to presentation secondary to biopsy-proven focal segmental glomerulosclerosis (FSGS), coronary artery disease, left atrial enlargement due to pulmonic stenosis, progressive sensorineural hearing loss 10 years prior and subsequent placement of a right cochlear implant, hypertension, and type 2 diabetes mellitus for the last year. At presentation, the patient's medications included cotrimoxazole prophylaxis, mycophenolate mofetil, tacrolimus, insulin, and folic acid. On examination, she was of short stature and had a low-grade fever and a left homonymous hemianopsia (L-HH). Within the next 3 weeks, she subsequently developed further visual disturbance to the point of being cortically blind in addition to new left upper extremity paresthesias. Initial CT head scan showed a subacute right occipital infarct and bilateral basal ganglia calcification. Subsequent CT imaging done 3 weeks later demonstrated interval development of new left temporoparietal and left occipital infarcts (figure, A). CT angiogram showed intracranial stenoses affecting basilar artery, both posterior cerebral arteries, and to a lesser degree bilateral anterior cerebral arteries and middle cerebral arteries, suggestive of possible atherosclerosis, but were not believed to be hemodynamically significant (figure, B). Due to her cochlear implant, significant streak artifact affected the interpretation of her CT scans and precluded her from obtaining an MRI.

Risk of progressive hearing loss in untreated superior semicircular canal dehiscence.

Patients with incidental or minimally symptomatic superior semicircular canal dehiscence (SSCD) are usually observed, without surgical repair. However, it remains unknown whether a labyrinthine fistula of the superior semicircular canal is associated with progressive conductive or sensorineural hearing loss over time. Retrospective review at two tertiary care academic referral centers. Adults analyzed were diagnosed with SSCD by high-resolution temporal bone computed tomography and vestibular evoked myogenic potential testing and observed with a minimum of two sequential audiograms. Patients with other potential causes of hearing impairment were excluded. A total of 40 ears in 30 adult patients (median age: 59 years; 63% female) were analyzed. Median audiometric follow-up was 23 months (range 1-136 months). None experienced a sudden hearing loss over the follow-up period. In patients with audiometric follow-up of at least 20 months (median 34 months), the median change in air-conduction pure tone average and air-bone gap was 0.9 decibels (dB) per year (interquartile range [IQR] 0-2.1) and 0.7 dB per year (IQR 0-2.0), respectively. Speech discrimination scores did not differ when comparing median initial (100%) and median final (98%) scores (P = 0.77). There was no statistically significant change in bone-conduction thresholds at 0.5, 1, 2, and 4 kHz over the period of observation. The risk of progressive hearing loss with observed SSCD is low during short- and intermediate-term follow-up. Further studies are necessary to determine whether late hearing loss occurs. Such information may be critical toward patient counseling regarding the need for and timing of surgery. 4. Laryngoscope, 127:1181-1186, 2017.

Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice

The TPRN gene encodes taperin, which is prominently present at the taper region of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177–187 in exon 1 of TPRN, which results in a truncated form of taperin protein. Heterozygous TPRN+/− mice showed apparently normal auditory phenotypes to their wide-type (WT) littermates. Homozygous TPRN−/− mice exhibited progressive sensorineural hearing loss as reflected by auditory brainstem response to both click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60). Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell numbers in the cochlea between TPRN−/− mice and WT mice under light microscope. However, scanning electronic microscopy revealed progressive degeneration of inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to scattered absence at P15 and further to substantial loss at P30. The outer hair cell stereocilia also showed progressive degeneration, though much less severe, Collectively, we conclude that taperin plays an important role in maintenance of hair cell stereocilia. Establishment of TPRN knockout mice enables further investigation into the function of this gene.

Ear health and hearing surveillance in girls and women with Turner's syndrome: recommendations from the Turner's Syndrome Support Society

Turner's syndrome (TS) is a common chromosomal disorder, affecting one in 2000 newborn girls, in which part or all of one X chromosome is missing. Ear and hearing problems are very common in girls and women with TS. The aim of this review was to review the published literature to suggest recommendations for otological health surveillance. A keyword search of Ovid Medline was performed for published literature on the subject and evidence rated according to the GRADE criteria. Middle ear disorders are very common and persistent in girls and women with TS as are progressive sensorineural hearing loss and balance disorders. Otolaryngologists should be aware of the high prevalence and challenging nature of all forms of ear disease in individuals with TS. Early intervention may offer benefits to health and education, and we advocate routine lifelong annual hearing screening in this group.

A Novel Asp121Asn Mutation of Myelin Protein Zero Is Associated with Late-Onset Axonal Charcot-Marie-Tooth Disease, Hearing Loss and Pupil Abnormalities.

Myelin protein zero (MPZ) is a major component of compact myelin in peripheral nerves. Mutations in MPZ have been associated with different Charcot–Marie–Tooth disease (CMT) phenotypes (CMT1B, CMT2I/J, CMTDI), Dejerine–Sottas syndrome, and congenital hypomyelination neuropathy. Here, we report phenotypic variability in a four-generation Chinese family with the MPZ mutation Asp121Asn. Genetic testing was performed on nine family members and 200 controls. Clinical, electrophysiological and skeletal muscle MRI assessments were available for review in six family members. A novel heterozygous missense mutation, Asp121Asn, was observed in five affected members of the family. Unaffected relatives and 200 normal controls were without the mutation. Four of the affected members of the family displayed late-onset, predominantly axonal sensory and motor neuropathy, pupil abnormalities, and progressive sensorineural hearing loss. One young affected member presented with Argyll–Robertson pupils and diminished deep tendon reflexes in the lower limbs. The MPZ mutation Asp121Asn may be associated with late-onset axonal neuropathy, early onset hearing loss and pupil abnormalities. Our report expands the number and phenotypic spectrum of MPZ mutations.

Association ofTMTC2With Human Nonsyndromic Sensorineural Hearing Loss

Sensorineural hearing loss (SNHL) is commonly caused by conditions that affect cochlear structures or the auditory nerve, and the genes identified as causing SNHL to date only explain a fraction of the overall genetic risk for this debilitating disorder. It is likely that other genes and mutations also cause SNHL. To identify a candidate gene that causes bilateral, symmetric, progressive SNHL in a large multigeneration family of Northern European descent. In this prospective genotype and phenotype study performed from January 1, 2006, through April 1, 2016, a 6-generation family of Northern European descent with 19 individuals having reported early-onset hearing loss suggestive of an autosomal dominant inheritance were studied at a tertiary academic medical center. In addition, 179 unrelated adult individuals with SNHL and 186 adult individuals reporting nondeafness were examined. Sensorineural hearing loss. Nine family members (5 women [55.6%]) provided clinical audiometric and medical records that documented hearing loss. The hearing loss is characterized as bilateral, symmetric, progressive SNHL that reached severe to profound loss in childhood. Audiometric configurations demonstrated a characteristic dip at 1000 to 2000 Hz. All affected family members wear hearing aids or have undergone cochlear implantation. Exome sequencing and linkage and association analyses identified a fully penetrant sequence variant (rs35725509) on chromosome 12q21 (logarithm of odds, 3.3) in the TMTC2 gene region that segregates with SNHL in this family. This gene explains the SNHL occurrence in this family. The variant is also associated with SNHL in a cohort of 363 unrelated individuals (179 patients with confirmed SNHL and 184 controls, P = 7 × 10-4). A previously uncharacterized gene, TMTC2, has been identified as a candidate for causing progressive SNHL in humans. This finding identifies a novel locus that causes autosomal dominant SNHL and therefore a more detailed understanding of the genetic basis of SNHL. Because TMTC2 has not been previously reported to regulate auditory function, the discovery reveals a potentially new, uncharacterized mechanism of hearing loss.

Isolated cochlear neuritis from varicella reactivation mimicking a vestibular schwannoma.

We present a case of a patient with progressive unilateral sensorineural hearing loss and tinnitus with internal auditory canal enhancement on magnetic resonance imaging (MRI) secondary to isolated cochlear neuritis from varicella reactivation. MRI following antiviral treatment showed resolution of enhancement. Varicella reactivation is commonly seen in the form of Ramsay Hunt syndrome, which is known to produce abnormal MRI enhancement from facial and vestibulocochlear neuritis; however, its characteristic clinical signs aid the diagnosis. This case is unique in that the only manifestation of varicella infection was unilateral hearing loss. This case outlines the importance of maintaining a broad differential diagnosis in the evaluation of unilateral hearing loss as well as recognizing the limited specificity of MRI.

Presbycusis - Age Related Hearing Loss

Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately.

Platinum-induced ototoxicity: a review of prevailing ototoxicity criteria

The antineoplastic agent's cisplatin and carboplatin are widely used as they are highly effective. Unfortunately, ototoxicity is a frequently encountered side effect of platinum-based chemotherapy. Clinically, patients generally develop a progressive, bilateral, and irreversible sensorineural hearing loss. With rising cancer survival rates, a greater proportion of patients are living with the side effects of their chemotherapy treatments. Consequently, the quality of life of cancer survivors has now become a major concern for clinicians. Various classification systems are currently available to grade side effects and provide a guideline for subsequent treatments. An extensive review of the literature revealed that a variety of criteria are used worldwide for grading platinum-induced hearing loss in children and adults, including the National Cancer Institute criteria, Brock's grading system, the American Speech-Hearing-Language Association criteria, the World Health Organization criteria, the Pediatric Oncology Group criteria, and the Muenster classification. Less commonly used criteria include the Chang classification, the Functional Hearing Loss scale, the HIT system (German Hirntumor study grading system), and most recently, the International Society of Pediatric Oncology Boston ototoxicity grading scale. The objective of this review is to evaluate the commonly used ototoxicity criteria and discuss their benefits and limitations.

Sequencing of exons 4, 5, 12 of COCH gene in patients with postlingual sensorineural hearing loss accompanied by vestibular lesion.

IntroductionMutations at the DFNA9 locus on chromosome 14q12 are the third most common form of DFNA hearing loss, which is clinically characterized by late onset (in adulthood) progressive sensorineural hearing loss accompanied by vestibular dysfunction. The aim of the study was to search for COCH gene mutations (P51S, V66G, G87W, G88E, V104del, I109N, W117R, A119T, M512T, C542Y) in patients with severe or profound sensorineural hearing loss accompanied by a vestibular lesion.Material and methodsThe study was based on a group of 30 patients. Qualification criteria comprised the presence of progressive postlingual, severe to profound sensorineural hearing loss with tinnitus, early age of sensorineural hearing loss onset, before the 40th year of life, and a positive family history of early onset hearing loss. All patients were diagnosed with peripheral vestibular lesions.ResultsThe authors did not find P51S, V66G, G87W, G88E, V104del, I109N, W117R, A119T, M512T, or C542Y mutations in the COCH gene in the tested group (no differences were found in the nucleotide sequences of exomes 4, 5 and 12 when compared to the published cDNA sequence of the COCH gene).ConclusionsNo cochlin mutations were found in the group of patients with severe to profound sensorineural hearing impairment accompanied by a vestibular lesion. The COCH gene needs further exploration and analysis of genotype-phenotype correlations.

An allograft mouse model for the study of hearing loss secondary to vestibular schwannoma growth.

Vestibular schwannoma is a benign neoplasm arising from the Schwann cell sheath of the auditory-vestibular nerve. It most commonly affects both sides in the genetic condition Neurofibromatosis type 2, causing progressive high frequency sensorineural hearing loss. Here, we describe a microsurgical technique and stereotactic coordinates for schwannoma cell grafting in the vestibular nerve region that recapitulates local tumor growth in the cerebellopontine angle and inner auditory canal with resulting hearing loss. Tumor growth was monitored by bioluminescence and MRI in vivo imaging, and hearing assessed by auditory brainstem responses. These techniques, by potentially enabling orthotopic grafting of a variety of cell lines will allow studies on the pathogenesis of tumor-related hearing loss and preclinical drug evaluation, including hearing endpoints, for NF2-related and sporadic schwannomas.

Mutations in Cockayne Syndrome-Associated Genes (Csa and Csb) Predispose to Cisplatin-Induced Hearing Loss in Mice.

Cisplatin is a common and effective chemotherapeutic agent, yet it often causes permanent hearing loss as a result of sensory hair cell death. The causes of sensitivity to DNA-damaging agents in nondividing cell populations, such as cochlear hair and supporting cells, are poorly understood, as are the specific DNA repair pathways that protect these cells. Nucleotide excision repair (NER) is a conserved and versatile DNA repair pathway for many DNA-distorting lesions, including cisplatin-DNA adducts. Progressive sensorineural hearing loss is observed in a subset of NER-associated DNA repair disorders including Cockayne syndrome and some forms of xeroderma pigmentosum. We investigated whether either of the two overlapping branches that encompass NER, transcription-coupled repair or global genome repair, which are implicated in Cockayne syndrome and xeroderma pigmentosum group C, respectively, modulates cisplatin-induced hearing loss and cell death in the organ of Corti, the auditory sensory epithelium of mammals. We report that cochlear hair cells and supporting cells in transcription-coupled repair-deficient Cockayne syndrome group A (Csa(-/-)) and group B (Csb(-/-)) mice are hypersensitive to cisplatin, in contrast to global genome repair-deficient Xpc(-/-) mice, both in vitro and in vivo We show that sensory hair cells in Csa(-/-) and Csb(-/-) mice fail to remove cisplatin-DNA adducts efficiently in vitro; and unlike Xpc(-/-) mice, Csa(-/-) and Csb(-/-) mice lose hearing and manifest outer hair cell degeneration after systemic cisplatin treatment. Our results demonstrate that Csa and Csb deficiencies predispose to cisplatin-induced hearing loss and hair/supporting cell damage in the mammalian organ of Corti, and emphasize the importance of transcription-coupled DNA repair in the protection against cisplatin ototoxicity. The utility of cisplatin in chemotherapy remains limited due to serious side effects, including sensorineural hearing loss. We show that mouse models of Cockayne syndrome, a progeroid disorder resulting from a defect in the transcription-coupled DNA repair (TCR) branch of nucleotide excision repair, are hypersensitive to cisplatin-induced hearing loss and sensory hair cell death in the organ of Corti, the mammalian auditory sensory epithelium. Our work indicates that Csa and Csb, two genes involved in TCR, are preferentially required to protect against cisplatin ototoxicity, relative to global genome repair-specific elements of nucleotide excision repair, and suggests that TCR is a major force maintaining DNA integrity in the cochlea. The Cockayne syndrome mice thus represent a model for testing the contribution of DNA repair mechanisms to cisplatin ototoxicity.

Late onset and high-frequency dominant hearing loss in a family with MYH9 disorder.

MYH9 disorder is a rare autosomal-dominant disorder. We previously reported that it is caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9 disorder causes congenital macrothrombocytopenia accompanied by progressive sensorineural hearing loss, nephropathy, and cataract. However, there are few reports that describe the audiological features of MYH9 disorder. The objective of this study was to characterize auditory and other phenotypes of patients with MYH9 disorder. We examined nine subjects from one Japanese family. Audiological, ophthalmological, hematological, and imaging examinations were used to assess clinical features. We carried out genetic analysis of the causative gene, MYH9. Five subjects exhibited macrothrombocytopenia and neutrophil cytoplasmic inclusion bodies. Immunofluorescence analysis of neutrophil NMMHC-IIA revealed abnormal type II localization. Two subjects had high-frequency dominant hearing loss, which was adult onset and progressive. Only one subject had cataract. MYH9 sequencing analysis of all thrombocytopenic subjects revealed a heterozygous c.4270G>A mutation in exon 30 (p.D1424N). We identified five patients with MYH9 disorder from the family. The hearing impairment associated with MYH9 disorder in this family was characterized as adult onset, progressive, and high-frequency dominant. Hematological manifestations of MYH9 disorder show complete penetrance, whereas extra-hematological manifestations show incomplete penetrance and variable expressivity in this family.

The case for earlier cochlear implantation in postlingually deaf adults

Objective: This paper aimed to estimate the difference in speech perception outcomes that may occur due to timing of cochlear implantation in relation to the progression of hearing loss. Design: Data from a large population-based sample of adults with acquired hearing loss using cochlear implants (CIs) was used to estimate the effects of duration of hearing loss, age, and pre-implant auditory skills on outcomes for a hypothetical standard patient. Study sample: A total of 310 adults with acquired severe/profound bilateral hearing loss who received a CI in Melbourne, Australia between 1994 and 2006 provided the speech perception data and demographic information to derive regression equations for estimating CI outcomes. Results: For a hypothetical CI candidate with progressive sensorineural hearing loss, the estimates of speech perception scores following cochlear implantation are significantly better if implantation occurs relatively soon after onset of severe hearing loss and before the loss of all functional auditory skills. Conclusions: Improved CI outcomes and quality of life benefit may be achieved for adults with progressive severe hearing loss if they are implanted earlier in the progression of the pathology.