Page 136 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 4
Participants and data sources
We included 60 adults (25 male) aged 16 years and older with a molecularly
confirmed 22q11.2 deletion that included the LCR22A-LCR22B region, using
standard methods.1 Participants were ascertained through referrals from
general practice (n=21), pediatrics (n=15), intellectual disability medicine
(n=11), clinical genetics (n=5), psychiatry (n=5), neurology (n=1), internal
medicine (n=1), and otolaryngology (n=1). In one patient, reasons for referral
included otolaryngological problems, i.e., globus pharyngeus. We excluded
subjects with no audiometry data (n=3), including one 39-year-old female
with history of hearing loss and hearing aids.
We used available medical information to record data on demographics,
molecular diagnosis, lifetime history of otolaryngological conditions,
and most recent FSIQ score. All adults were routinely evaluated by an
otolaryngologist and audiologist. Standard examinations included a semi-
structured interview, a complete ear-nose and throat examination, and
audiometric testing. Two had their most recent audiogram at MUMC+
before 2016.
Audiological assessments
Data for audiological assessments included pure-tone air and bone-
conduction audiometry. Unaided ear-specific hearing thresholds were
measured from 0.25 to 8 kHz with pure-tone audiometry. Presence/absence
and severity of hearing loss were classified with the Muenster classification
because this classification includes criteria for high-frequency hearing loss
(Table 1),12 that was often found in adults with 22q11.2DS. Thus, hearing
loss was defined as having loss with a severity of grade two or higher.12
Type and laterality of hearing loss, frequency ranges and audiometric
configuration were classified using the European Working Group on the
Genetics of Hearing Impairment definitions.13 Because most audiometric
abnormalities in the 22q11.2DS sample concerned the high-frequencies,
adaptations were made to these definitions, i.e.: 1) we averaged the pure-
tone hearing thresholds over 0.5, 1, 2 and 4 kHz instead of 0.5, 1 and 2
kHz, to define type and laterality of hearing loss, 2) we introduced u-shaped
configurations in order to classify individuals that performed best at the
mid-frequencies, and 3) in addition to the standard criteria for gently and
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