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Hearing loss and otolaryngological conditions1434and type 2 diabetes mellitus,20, 21 and multimorbidity and polypharmacy are often seen in 22q11.2DS at a relatively young age.22 Third, genetic susceptibility should be considered.19 For example, young-onset and age-related hearing loss has been reported in other genetic neurodevelopmental disorders, such as in Down syndrome,23 and Turner syndrome.24 Importantly, findings may be specific per genetic variant. When comparing the sensory thresholds found in Turner syndrome to those reported in 22q11.2DS it is striking that adults with Turner syndrome scored worst at the mid-frequency (2 kHz),25 whereas adults with 22q11.2DS performed best at the mid-frequencies and worst at the highest and lowest frequencies.Genes that may possibly play a role in 22q11.2DS include TBX1 and genes involved in mitochondrial function.17, 26 TBX1 is involved in the development of the vascular system including the stria vascularis (an important cochlear structure that is rich in vascular tissue), the central nervous system, and the semicircular canal.17, 27 In mice with a homozygous missense mutation in Tbx1inner ear malformations, an undeveloped stria vascularis, and deafness have been found.17 Other candidate genes include those involved in mitochondrial function; at least six lie within the 22q11.2 region.28 Mitochondrial dysfunction and oxidative stress have been proposed as possible contributors to degenerative changes in the cochlear duct (i.e., in the stria vascularis, hair cells and neurons) which may result in age-related hearing loss.26Clinical implications of the hearing findingsHigh-frequency hearing loss makes it more difficult to understand speech with background noise, for example during group conversations, and to localize sounds.19 It often precedes, and is a predictor of, hearing loss at the lower frequencies.29 Similarly, loss at the mid-frequencies may negatively affect daily life functioning by reduced understanding of speech or hearing in traffic. If diagnosed late, hearing loss may contribute to the development of depressive symptoms, stress, anxiety, social isolation and reduced quality of life.30, 31 Early identification of hearing loss enables interventions through adjustments to someone’s work or living environment, and/or the prescription of hearing aids, if indicated. Therefore, given the high proportion of adults with 22q11.2DS with high-frequency hearing loss, we recommend periodic audiological screening (e.g., every five years), including highfrequency ranges (8 kHz), in all adults with 22q11.2DS.