Page 145 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Hearing loss and otolaryngological conditions
and 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 Tbx1
inner 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.26
Clinical implications of the hearing findings
High-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 high-
frequency ranges (8 kHz), in all adults with 22q11.2DS.
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