Etiology of Childhood Profound Sensorineural Hearing Loss: The Role of Hearing Loss Gene Panel Testing.

OBJECTIVE: Establishing the cause of hearing loss (HL) is important and rewarding, though not without its challenges. While our ability to identify the etiology for HL has improved with advances in scientific knowledge, a significant proportion of cases remain of unknown etiology. Recent protocol changes within the NHS Genomic Medicine Service support the utilization of the HL gene panel test, rather than individual gene tests. In light of these changes, determining the yield of these more extensive panel tests is important in informing future practice. STUDY DESIGN: Retrospective study. SETTING: The Cochlear Implant (CI) Department at Great Ormond Street Hospital (GOSH). METHODS: Four hundred seventy-six children with profound HL were identified from a database of referrals to the GOSH CI Department. Data on etiology of HL including genetic diagnosis was collected from hospital notes on an electronic patient records system and hospital genetics database. RESULTS: We identified a positive result in 163/476 (34%) cases through the gene panel test, representing an additional 19% yield to current level 1 investigations. Genetic HL, including both syndromic (including those not covered by the HL gene panel) and nonsyndromic (209/476, 44%) was the most common etiology in our cohort. Perinatal, intrauterine, ototoxicity, meningitis, and encephalitis categories altogether comprised 97/476 (20%) cases. CONCLUSION: Gene panel testing provides significant additional yield over current level 1 investigations which include GJB2 testing only. This has far-reaching implications for how we optimize investigations into HL in children and counsel families, and for future early interventions.

Three New Mutations and Mild, Asymmetrical Phenotype in the Highly Distinctive LAMM Syndrome: A Report of Eight Further Cases.

Labyrinthine aplasia, microtia, and microdontia (LAMM) is an autosomal recessive condition causing profound congenital deafness, complete absence of inner ear structures (usually Michel's aplasia), microtia (usually type 1) and microdontia. To date, several families have been described with this condition and a number of mutations has been reported. We report on eight further cases of LAMM syndrome including three novel mutations, c. 173T>C p.L58P; c. 284G>A p.(Arg95Gln) and c.325_327delinsA p.(Glu109Thrfs*18). Congenital deafness was the primary presenting feature in all affected individuals and consanguinity in all but two families. We compare the features in our patients to those previously reported in LAMM, and describe a milder, asymmetrical phenotype associated with FGF3 mutations.

Subjective visual vertical and horizontal: effect of the preset angle.

OBJECTIVES: (1) To study the subjective visual vertical (SVV) and subjective visual horizontal (SVH) in patients with long-standing unilateral peripheral vestibular dysfunction (PVD) and unilateral Ménière's disease (MD) compared with controls. (2) To study the relationship between the direction of deviation of the linear marker (preset angle) and measures of SVV and SVH values. DESIGN: Prospective case-control study. SETTING: Outpatient clinic in a tertiary neuro-otology department. PATIENTS: Seventeen healthy volunteers (mean age, 35.5 years), 9 patients with PVD (mean age, 43.1 years), and 10 patients with MD (mean age, 50.7 years) were included in the analysis. INTERVENTIONS: All subjects had a detailed neuro-otological evaluation. Twelve replicate readings of SVV and SVH were taken for each subject, with random preset angles, 6 in the clockwise and 6 in the counterclockwise direction. MAIN OUTCOME MEASURE: The SVV and SVH values were correlated with clinical features and the direction of the preset angle. RESULTS: The 2 subjects with PVD who had abnormal mean SVV and SVH values had symptoms of dysequilibrium and otolithic involvement. The 5 patients in the MD group who had abnormal mean SVV and SVH values had either recent acute vertiginous attacks or total canal paresis on the affected side. A previously unreported finding, to our knowledge, is that the SVV value depends on the direction of the preset angle in all subject groups, more so in the PVD and MD groups compared with controls. The SVV is inclined toward the direction of the preset angle. A weaker relation is seen between the SVH and preset angle. CONCLUSION: The preset angle should be considered when comparing SVV and SVH values.