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Here, we show that mouse mutants with either a gain or loss of function of the T-Box transcription factor gene, Tbx1, which lies within the 22q11.2 region and is responsible for most of the syndromic defects, exhibit inner ear defects and hyperactivity. Children with the 22q11.2 deletion or duplication syndromes often display hearing loss and behavioral disorders, including ADHD and anxiety-related disorders. Potential explanations for these elevated rates and the heterogeneity of behavioral disorders associated with deafness have usually focused on socio-environmental rather than biological effects. The Severity of Vestibular Dysfunction in Deafness as a Determinant of Comorbid Hyperactivity or Anxiety.Īntoine, Michelle W Vijayakumar, Sarath McKeehan, Nicholas Jones, Sherri M Hébert, Jean MĪttention-deficit/ hyperactivity disorder (ADHD) and anxiety-related disorders occur at rates 2-3 times higher in deaf compared with hearing children.

Using conditional genetic approaches in mice, the authors show that (1) inner ear dysfunction due to either Tbx1 or Slc12a2 mutations cause hyperactivity (2) it is vestibular dysfunction, which frequently co-occurs with deafness but often remains undiagnosed, rather than auditory dysfunction that causes hyperactivity and anxiety-related symptoms and (3) the severity of SIGNIFICANCE STATEMENT This study examines the biological rather than socio-environmental reasons why hyperactivity and anxiety disorders occur at higher rates in deaf individuals. Together, these findings highlight a biological link between inner ear dysfunction and behavioral disorders and how sensory abnormalities can contribute to the etiology of disorders traditionally considered of cerebral origin. Furthermore, we show that (1) inner ear dysfunction due to the tissue-specific loss of Tbx1 or Slc12a2, which encodes a sodium-potassium-chloride cotransporter and is also necessary for inner ear function, causes hyperactivity (2) vestibular rather than auditory failure causes hyperactivity and (3) the severity rather than the age of onset of vestibular dysfunction differentiates whether hyperactivity or anxiety co-occurs with inner ear dysfunction.

The Severity of Vestibular Dysfunction in Deafness as a Determinant of Comorbid Hyperactivity or AnxietyĪttention-deficit/ hyperactivity disorder (ADHD) and anxiety-related disorders occur at rates 2–3 times higher in deaf compared with hearing children.