International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Hearing loss in the pediatric patient.

OBJECTIVE: To provide recommendations for the workup of hearing loss in the pediatric patient. METHODS: Expert opinion by the members of the International Pediatric Otolaryngology Group. RESULTS: Consensus recommendations include initial screening and diagnosis as well as the workup of sensorineural, conductive and mixed hearing loss in children. The consensus statement discusses the role of genetic testing and imaging and provides algorithms to guide the workup of children with hearing loss. CONCLUSION: The workup of children with hearing loss can be guided by the recommendations provided herein.

Novel partial duplication of EYA1 causes branchiootic syndrome in a large Brazilian family.

OBJECTIVE: To identify novel genetic causes of syndromic hearing loss in Brazil. DESIGN: To map a candidate chromosomal region through linkage studies in an extensive Brazilian family and identify novel pathogenic variants using sequencing and array-CGH. STUDY SAMPLE: Brazilian pedigree with individuals affected by BO syndrome characterized by deafness and malformations of outer, middle and inner ear, auricular and cervical fistulae, but no renal abnormalities. RESULTS: Whole genome microarray-SNP scanning on samples of 11 affected individuals detected a multipoint Lod score of 2.6 in the EYA1 gene region (chromosome 8). Sequencing of EYA1 in affected patients did not reveal pathogenic mutations. However, oligonucleotide-array-CGH detected a duplication of 71.8Kb involving exons 4 to 10 of EYA1 (heterozygous state). Real-time-PCR confirmed the duplication in fourteen of fifteen affected individuals and absence in 13 unaffected individuals. The exception involved a consanguineous parentage and was assumed to involve a different genetic mechanism. CONCLUSIONS: Our findings implicate this EYA1 partial duplication segregating with BO phenotype in a Brazilian pedigree and is the first description of a large duplication leading to the BOR/BO syndrome.

FGF23 deficiency leads to mixed hearing loss and middle ear malformation in mice.

Fibroblast growth factor 23 (FGF23) is a circulating hormone important in phosphate homeostasis. Abnormal serum levels of FGF23 result in systemic pathologies in humans and mice, including renal phosphate wasting diseases and hyperphosphatemia. We sought to uncover the role FGF23 plays in the auditory system due to shared molecular mechanisms and genetic pathways between ear and kidney development, the critical roles multiple FGFs play in auditory development and the known hearing phenotype in mice deficient in klotho (KL), a critical co-factor for FGF23 signaling. Using functional assessments of hearing, we demonstrate that Fgf[Formula: see text] mice are profoundly deaf. Fgf[Formula: see text] mice have moderate hearing loss above 20 kHz, consistent with mixed conductive and sensorineural pathology of both middle and inner ear origin. Histology and high-voltage X-ray computed tomography of Fgf[Formula: see text] mice demonstrate dysplastic bulla and ossicles; Fgf[Formula: see text] mice have near-normal morphology. The cochleae of mutant mice appear nearly normal on gross and microscopic inspection. In wild type mice, FGF23 is ubiquitously expressed throughout the cochlea. Measurements from Fgf[Formula: see text] mice do not match the auditory phenotype of Kl-/- mice, suggesting that loss of FGF23 activity impacts the auditory system via mechanisms at least partially independent of KL. Given the extensive middle ear malformations and the overlap of initiation of FGF23 activity and Eustachian tube development, this work suggests a possible role for FGF23 in otitis media.

Saethre-Chotzen syndrome, Pro136His TWIST mutation, hearing loss, and external and middle ear structural anomalies: report on a Brazilian family.

OBJECTIVE: To describe the clinical, speech, hearing, and imaging findings in three members of a Brazilian family with Saethre-Chotzen syndrome (SCS) who presented some unusual characteristics within the spectrum of the syndrome. DESIGN: Clinical evaluation was performed by a multidisciplinary team. Direct sequencing of the polymerase chain reaction-amplified coding region of the TWIST1 gene, routine and electrophysiological hearing evaluation, speech evaluation, and imaging studies through computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed. RESULTS: TWIST1 gene analysis revealed a Pro136His mutation in all patients. Hearing evaluation showed peripherial and mixed hearing loss in two of the patients, one of them with severe unilateral microtia. Computed tomography scan showed structural middle ear anomalies, and MRI showed distortion of the skull contour as well as some of the brain structures. CONCLUSIONS: We report a previously undescribed TWIST1 gene mutation in patients with SCS. There is evidence that indicates hearing loss (conductive and mixed) can be related both with middle ear (microtia, high jugular bulb, and enlarged vestibules) as well as with brain stem anomalies. Here we discuss the relationship between the gene mutation and the clinical, imaging, speech, and hearing findings.

How to prevent a stapes gusher.

A stapes gusher is the result of a congenital inner ear anomaly showing at tone audiometry a conductive or mixed hearing loss. The conductive part of the hearing loss could lead to the thought to explore the middle ear. The congenital origin should lead to a high resolution. CT-scanning to evaluate a widening of the internal acoustic canal. Repeated audiometry could show especially a large conductive impairment in the lowest frequencies with a closure of the airbone gap at 2 khz and a high sensorineural high frequency loss at 4 and 8 khz. Contralateral stapedial reflexes may be present. Since the x-recessive mixed deafness syndrome (DFN3) frequently involves males with an early childhood hearing impairment, clinical suspicion should be high. When stapes surgery is considered a precise medical history is essential regarding on the start of the hearing impairment. A continuous suspicion will guide to the audiological, radiological and molecular genetic clues to trace the correct diagnosis before embarking on stapes surgery.

Hereditary bilateral conductive hearing loss caused by total loss of ossicles: a report of familial expansile osteolysis.

OBJECTIVE: The objective of this study was to report on three members of a family with familial expansile osteolysis; the important point about these patients was that none of them had middle-ear ossicles. STUDY DESIGN AND SUBJECTS: A retrospective case review including three cases with familial expansile osteolysis. SETTING: Department of Otolaryngology in a tertiary referral center. INTERVENTIONS: Each patient underwent computerized tomography of the temporal bone in the coronal view, audiometric and tympanometric evaluations, biochemical investigation, whole body isotope scans by Tc-99 mMDP and X-ray. Also the patients' pedigree was studied. Two of the patients had exploratory middle-ear surgery as well. RESULTS: The temporal-bone computed-tomography scan in the coronal view of all three patients and also exploratory middle-ear surgery, which was done on two of the patients, showed no ossicles in the middle ear of either ear in all three cases. This feature hadn't been reported in previous studies. Hearing loss was revealed in the medical histories since childhood. Audiometry indicated mild to moderate conductive and mixed hearing loss and also an AD-type tympanogram pattern along with an absence of acoustic reflexes in both ears of the cases. Both serum alkaline phosphatase and hydroxyproline levels were elevated. There was an increase in uptake and activity at multiple foci of the whole skeleton. No improvement in hearing thresholds was obtained after reconstruction of the middle ear. CONCLUSION: The total absence of middle-ear ossicles can probably be regarded as a new symptom in some patients with familial expansile osteolysis. Common ossiculoplasty for improving the hearing thresholds in this condition may be unsuccessful; therefore, both surgeons and patients must be completely aware of the contingent undesirable results.