Xuan Wu

Magnetic resonance imaging-detected inner ear hemorrhage as a potential cause of sudden sensorineural hearing loss.

PURPOSE The aim of this study is to assess the value of magnetic resonance imaging in identifying the etiology of sudden sensorineural hearing loss, and to correlate the high signals in the labyrinth with clinical features to identify if inner ear hemorrhage could be implicated. MATERIALS AND METHODS In this retrospective study, inner ear magnetic resonance imaging was given to 112 patients with sudden sensorineural hearing loss in the First Affiliated Hospital of Sun Yat-sen University from 2011 to 2012. The clinical features of patients with high signals in the labyrinth on magnetic resonance imaging were analyzed. RESULTS Abnormal magnetic resonance images were identified in 13 (11.6%) patients. Retrocochlear pathology was found in six patients, including two cases of lacunar infarction, one case of multiple ischemias in the brainstem and bilateral centrum semiovale, two cases of acoustic neuroma, and one case of inner ear hemangioma. There were seven cases showing high signals in the labyrinth on unenhanced T1-weighted and fluid-attenuated inversion recovery images. Clinical features of these seven patients were characterized by irreversible profound hearing impairment and vestibular dysfunction. These findings were consistent with the hypothesis that their symptoms were caused by an inner ear hemorrhage. CONCLUSION The results indicate the importance of magnetic resonance imaging in sudden sensorineural hearing loss in patients. Moreover, patients with vestibular dysfunction and sudden profound hearing loss may have an inner ear hemorrhage evident by interpreting clinical and magnetic resonance imaging results.

De novo dominant mutation of SOX10 gene in a Chinese family with Waardenburg syndrome type II

OBJECTIVE Waardenburg syndrome is a rare genetic disorder, inherited as an autosomal dominant trait. The condition is characterized by sensorineural hearing loss and pigment disturbances of the hair, skin, and iris. The de novo mutation in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen. The present study aimed to identify the genetic causes of Waardenburg syndrome type II in a Chinese family. METHODS Clinical and molecular evaluations were conducted in a Chinese family with Waardenburg syndrome type II. RESULTS A novel SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not observed in the parents and sister of the proband, indicating that the mutation has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10 gene, disrupted normal amino acid coding from Leu87, leading to premature termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was inferred to be partially impaired. CONCLUSION The novel heterozygous c.259-260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg syndrome in the proband. The clinical and genetic characterization of this family would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome type II. Moreover, the de novo pattern expanded the mutation data of SOX10.

Genetic counseling for a three-generation Chinese family with Waardenburg syndrome type II associated with a rare SOX10 mutation

OBJECTIVE Waardenburg syndrome is clinically and genetically heterogeneous. The SOX10 mutation related with Waardenburg syndrome type II is rare in Chinese. This study aimed to uncover the genetic causes of Waardenburg syndrome type II in a three-generation family to improve genetic counseling. METHODS Complete clinical and molecular evaluations were conducted in a three-generation Han Chinese family with Waardenburg syndrome type II. Targeted genetic counseling was provided to this family. RESULTS We identified a rare heterozygous dominant mutation c.621C>A (p.Y207X) in SOX10 gene in this family. The premature termination codon occurs in exon 4, 27 residues downstream of the carboxyl end of the high mobility group box. Bioinformatics prediction suggested this variant to be disease-causing, probably due to nonsense-mediated mRNA decay. Useful genetic counseling was given to the family for prenatal guidance. CONCLUSION Identification of a rare dominant heterozygous SOX10 mutation c.621C>A in this family provided an efficient way to understand the causes of Waardenburg syndrome type II and improved genetic counseling.

Delayed Recovery in Pediatric Sudden Sensorineural Hearing Loss Predicted via Magnetic Resonance Imaging

Objectives: To evaluate the potential origins via magnetic resonance imaging and the relevant hearing recovery course of pediatric sudden sensorineural hearing loss. Methods: We retrospectively analyzed data of 25 pediatric patients from our center with sudden sensorineural hearing loss from January 2011 to December 2016. All individuals were closely followed up at baseline and 1 and 6 months. Results: Magnetic resonance imaging identified presumed causes in 9 cases, 5 of which showed intralabyrinthine hyperintensity, suggesting presumptive intralabyrinthine hemorrhage. The remaining 20 patients showed no hyperintensity. Restoration of hearing and speech discrimination abilities were noted in these 25 children at 6 months versus the initial levels (74.2 ± 22.6 vs 93.5 ± 20.5 dB, p = .000, and 45.8 ± 36.0 vs. 18.3 ± 22.1%, p = .004, respectively). The prognosis of the individuals with intralabyrinthine hemorrhage were superior in terms of frequency and hearing threshold at 6 months compared with that of the no-hemorrhage participants. Word recognition scores improved in either studied group. Conclusion: The potential recovery of hearing in children raises concerns about very early surgical intervention within the first 6 months. Rational imaging and sequential audiometric evaluation to monitor the progression of recovery may be beneficial.

GJB3/GJB6 screening in GJB2 carriers with idiopathic hearing loss: Is it necessary?

Genetic analysis detected excessive mono‐allelic recessive GJB2 mutations in individuals with idiopathic deafness; the remaining alleles in trans/cis are underdetermined. The aim of this study was to assess the contributions of variants in GJB3 or GJB6 to non‐syndromic sensorineural hearing impairment (NSHI) in Chinese patients with mono‐allelic GJB2 mutations.

Targeted next generation sequencing reveals OTOF mutations in auditory neuropathy spectrum disorder

OBJECTIVE To study the genetic etiology of auditory neuropathy spectrum disorder (ANSD) in a Chinese family and perform a literature review of OTOF mutations and cochlear implantation (CI). METHODS Sequential targeted next generation sequencing (NGS) and CI was performed for the proband. Further, 50 DNA samples from unrelated families with nonsyndromic deafness were examined for frequency determination. The impact of OTOF mutations on hearing recovery after CI was assessed through the literature survey. RESULTS In the proband, the targeted NGS panel revealed five suspected variants in four genes (OTOF, EYA4, PCDH15, and GIPC3), of which two mutations-c.5098G > C (p.Glu1700Gln) and c.1702C > T (p.Arg568Trp)-in the OTOF gene were found to be correlated with ANSD. The c.5098G > C allele was identified in only one child from the 50 unrelated participants. The probands hearing and speech abilities were restored 2 years after the surgery. Most ANSD patients (90.9%; 30/33) with OTOF mutations have acceptable surgical outcomes, as indicated by existing reports. CONCLUSIONS Our results support the feasibility of CI for patients with ANSD and OTOF mutations, and this hypothesis was supported by the review of existing data. A larger number of cases studies is required to determine possible modifies on the prognosis of surgery.

Side-related differences in sudden sensorineural hearing loss in children

OBJECTIVE Most studies on sudden sensorineural hearing loss (SSNHL) do not differentiate the outcomes within varied affected ears in children. The present study was designed to determine the clinical differences between unilateral and bilateral SSNHL in children. METHODS The clinical data, from a total of 101 pediatric patients with SSNHL, was retrospectively analyzed from January 2003 to December 2016. The main outcome measures included basic characteristics, etiology, clinical symptoms and treatment courses. RESULTS When the bilateral group (n = 28) was compared to the unilateral group (n = 73), neither gender nor onset of SSNHL was significantly different (p > 0.05 each); However, bilateral SSNHL tended to occur in younger ages (8.1 ± 4.0 yrs), with higher percentages of suspected etiologies (50%) and proportion of profound deafness (55.4%, p < 0.05 each). The short-term recovery rate was superior in the unilateral cases over the bilateral cases (37.0% vs. 12.5%, p < 0.05). Milder initial hearing threshold, early onset of treatment (5.6 ± 4.8 days) with unilateral involvement and an older age (11.3 ± 3.0 yrs) in bilaterally affected cases were associated with a better prognosis in this cohort. In addition, the unilateral group showed comparable outcomes, when sub-analyzed by comparison to that in either left- (n = 42) or right-sided (n = 31) SSNHL. CONCLUSION Although bilateral and unilateral pediatric SSNHL could cause partial to complete cochlear lesion, they may be relevant to distinct backgrounds. Our data also provides valuable information about demographics and outcomes of SSNHL in children.

Audiological outcomes in sudden sensorineural hearing loss with presumed inner ear hemorrhage

OBJECTIVE To explore the hearing outcomes and prognostic factors in patients with sudden sensorineural hearing loss resulting from inner ear hemorrhage. METHODS 42 patients (22 male and 20 female) were recruited from January 2016 to December 2017. Intravenous methylprednisolone and/or intratympanic corticosteroid were used as salvage therapy. The main measures included systemic risk factors and audiometric outcomes as proposed by American Academy of Otolaryngology-Head and Neck Surgery Hearing Loss Scale. All individuals were assessed at baseline, discharge (2 weeks post-treatment) and at 1, 3 and 6 months. RESULTS The mean ages of patients were 39.3 ± 14.8 yrs. Cardiovascular disorders were seen in 19.0-33.3% of cases. Restoration of hearing and speech discrimination abilities were assessed at the first month post-treatment versus initial levels (95.5 ± 15.5 vs. 109.2 ± 9.6 dB, p = 0.000; and 17.6 ± 24.4 vs. 1.3 ± 4.0%, p = 0.003, respectively). Word recognition scores continued to recover at month 6 (38.7 ± 35.4%, p = 0.000), whereas puretone ceased to change (90.8 ± 16.2 dB, p = 0.139). The final percentages of complete, partial and no recovery were 0%, 57.1% and 42.9% respectively. The prognosis was independent of accompanying systemic risk factors as analyzed in this study. Intratympanic intervention was associated with improved word recognition scores, although intravenous corticosteroid was not. CONCLUSIONS Profound sudden sensorineural hearing loss caused by inner ear hemorrhage often has an unsatisfactory prognosis. However, this cohort did experience partial audiological recovery with delayed onset. Immediate and effective intratympanic corticosteroid may have therapeutic potential for this intractable disease.