Objective Ménière’s disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid (endolymph) volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Conventional imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many and typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies. Purpose The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.

CHD7 is a novel chromodomain gene mutated in 60%-80% of humans with CHARGE syndrome, a multiple congenital anomaly condition characterized by ocular coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and characteristic ear abnormalities including deafness. Phenotypic features of CHARGE are highly variable and incompletely penetrant. To explore developmental roles of CHD7, we generated mice carrying the Chd7(Gt) allele from a Chd7-deficient, gene-trapped lacZ reporter ES cell line. RT-PCR of embryo RNA demonstrated significantly reduced levels of wild-type transcript in Chd7(Gt/Gt) embryos. Chd7(Gt/Gt) embryos survive only up to embryonic day 10.5 (E10.5). Chd7(Gt/+) male and female mice are viable, small, and exhibit variable degrees of head-bobbing and circling, consistent with vestibular dysfunction. Paint-filling of E16.5 heterozygous inner ears revealed defects of the semicircular canals. The pattern of beta-galactosidase activity in Chd7(Gt/+) embryos mimics Chd7 mRNA expression in wild-type embryos, confirming the fidelity of the lacZ reporter. We observed tissue-specific beta-galactosidase in the E12.5 and E14.5 Chd7(Gt/+) brain, pituitary, ear, heart, and craniofacial structures, indicating survival of Chd7(Gt/+) cells in CHARGE-relevant organs. These studies demonstrate the utility of Chd7(Gt) as a reporter-tagged loss-of-function allele for future studies exploring developmental mechanisms of Chd7 deficiency.

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An elevated SP/AP ratio seems to be a consistent finding in SSCD syndrome and, like the other abnormal audiometric and electrophysiologic findings associated with the syndrome, normalizes after surgical correction. Elevation of the SP/AP ratio has historically been associated with endolymphatic hydrops. The present findings expand the differential diagnosis of an abnormal ECoG and may shed light on the origin of an elevated summating potential.

CHD7 is a chromodomain gene mutated in CHARGE syndrome, a multiple anomaly condition characterized by ocular coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear defects including deafness and semicircular canal dysgenesis. Mice with heterozygous Chd7 deficiency have circling behavior and semicircular canal defects and are an excellent animal model for exploring the pathogenesis of CHARGE features. Inner ear vestibular defects have been characterized in heterozygous Chd7-deficient embryos and early postnatal mice, but it is not known whether vestibular defects persist throughout adulthood in Chd7-deficient mice or whether the vestibular sensory epithelia and their associated innervation and function are intact. Here we describe a detailed analysis of inner ear vestibular structures in mature mice that are heterozygous for a Chd7-deficient, gene-trapped allele (Chd7(Gt/+)). Chd7(Gt/+) mice display variable asymmetric lateral and posterior semicircular canal malformations, as well as defects in vestibular sensory epithelial innervation despite the presence of intact hair cells in the target organs. These observations have important functional implications for understanding the clinical manifestations of CHD7 mutations in humans and for designing therapies to treat inner ear vestibular dysfunction.