Identification of causative genes for hereditary nonsyndromic hearing loss (NSHL) is important to decide treatment modalities and to counsel the patients. Due to the genetic heterogeneity in sensorineural genetic disorders, the high-throughput method can be adapted for the efficient diagnosis. To this end, we designed a new diagnostic pipeline to screen all the reported candidate genes for NSHL. For validation of the diagnostic pipeline, we focused upon familial NSHL cases that are most likely to be genetic, rather than to be infectious or environmental. Among the 32 familial NSHL cases, we were able to make a molecular genetic diagnosis from 12 probands (37.5%) in the first stage by their clinical features, characteristic inheritance pattern and further candidate gene sequencing of GJB2, SLC26A4, POU3F4 or mitochondrial DNA. Next we applied targeted resequencing on 80 NSHL genes in the remaining 20 probands. Each proband carried 4.8 variants that were not synonymous and had the occurring frequency of less than three among the 20 probands. These variants were then filtered out with the inheritance pattern of the family, allele frequency in normal hearing 80 control subjects, clinical features. Finally NSHL-causing candidate mutations were identified in 13(65%) of the 20 probands of multiplex families, bringing the total solve rate (or detection rate) in our familial cases to be 78.1% (25/32) Damaging mutations discovered by the targeted resequencing were distributed in nine genes such as WFS1, COCH, EYA4, MYO6, GJB3, COL11A2, OTOF, STRC and MYO3A, most of which were private. Despite the advent of whole genome and whole exome sequencing, we propose targeted resequencing and filtering strategy as a screening and diagnostic tool at least for familial NSHL to find mutations based upon its efficacy and cost-effectiveness.

With the advent of microdebriders and image guidance systems, endoscope-assisted surgery is now more widely used for the treatment of tumors involving the base of the skull. The aim of this study was to analyze the clinical features of tumors involving the anterior skull base and to evaluate the treatment outcomes according to the surgical approach, which included the traditional craniofacial resection (TCFR) and the endoscopic craniofacial resection with craniotomy (ECFR). Forty-six patients who underwent craniofacial resection from 1989 through 2006 at Seoul National University Hospital and Seoul National University Bundang Hospital were included in this study. Demographics, histology, surgical management, surgical outcomes, complications, and morbidity were analyzed. The number of malignant and benign lesions was 40 and 6 cases respectively. The most common diagnosis was olfactory neuroblastoma occurring in 41% of the cases followed by squamous cell carcinoma and malignant melanoma. Thirty-six patients underwent TCFR, while ECFR was performed with or without adjunctive chemotherapy or radiotherapy in 10 patients. The overall five-year survival rate for patients with malignant tumors of the anterior skull base was 47.4%. Out of 19 patients with olfactory neuroblastomas, 10 patients had TCFR and six among them died of their disease. Nine patients underwent ECFR, and none of them died of their disease. The ECFR group had lower morbidity and cosmetic deformity than did the TCFR group. The ECFR may be considered as an alternative option for the treatment of selected tumors with anterior skull base invasion. This approach offers the advantages of avoiding facial incisions with comparable treatment results.

Hearing in neonates and infants is crucial for their development of language and communication skills. Unless hearing loss is appropriately managed early, it can cause a significant socioeconomic burden considering its detrimental impact on the child's development and its common nature. It is also the most common congenital sensory deficit, with an approximate incidence of 1.5 per 1,000 newborns. Its etiologies are heterogeneous: genetic causes are reportedly involved in up to 80% of cases, while congenital cytomegalovirus infection is the leading environmental factor contributing to congenital hearing loss. The introduction of newborn hearing screening using automated auditory brainstem response and/or automated otoacoustic emission in many developed countries has helped detect and manage hearing loss early. Current auditory rehabilitation options such as cochlear implantation implementing cutting-edge technologies can treat almost all degrees of hearing loss, emphasizing the importance of early hearing detection and intervention. Rapidly developing genetic diagnostic technologies and future cutting-edge treatment options, including gene therapy, will shed light on the future management of hearing loss in neonates and infants.

Kim BJ, et al. Clin Exp Otorhinolaryngol. 2014 Jun;7(2):87-93. http://dx.doi.org/10.3342/ceo.2014.7.2.87