Page 205 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

General discussion and future perspectives
General discussion and future perspectives
The natural life course of most genetic neurodevelopmental disorders
(GNDs) has been understudied, resulting in a knowledge gap and health
disparities, particularly for manifestations at adult age.1 The studies included
in this thesis have contributed to our knowledge of prevalence rates and
characteristics of conditions including parkinsonism, otolaryngologic and
ophthalmic conditions and post-traumatic stress in adults with 22q11.2
deletion syndrome (22q11.2DS) and other GNDs. Most results were
obtained by routine examinations at specialized 22q11.2 clinics including
the expert center for adults at Maastricht University Medical Center and ‘s
Heeren Loo. In this chapter the clinical findings in adults with 22q11.2DS
and other GNDs are discussed, in addition to predictive markers and
pathophysiology of conditions at adult age, methodological considerations
and recommendations for clinical practice and future research.
Expanding the phenotype of adults with 22q11.2 deletion syndrome
Presented in chapters 3-5 and 7, adults with 22q11.2DS were found to
have an increased risk of early-onset Parkinson’s disease, hearing loss,
refractive errors and PTSD compared to the general population.2-5 There are
two important notes. First, results often showed a high variability among
adults with 22q11.2DS, for example in severity of hearing loss, refractive
errors and retinovascular parameters (chapter 6). This inter-individual
variability has also been reported in other conditions in 22q11.2DS and,
although contributors are not yet fully understood, may be related to the
many genes involved in the 22q11.2 deletion, additional genetic variants,
stochastic events during embryogenesis and environmental effects.6,
7 Second, an increased prevalence of these conditions in adults with
22q11.2DS compared to the general population does not implicate that
they are specific expressions of a 22q11.2 microdeletion. For example, a
comparable prevalence and type of hearing loss has also been found in
adults with Down syndrome,8 and children with an intellectual disability are
reported to have prevalence rates of strabismus and amblyopia comparable
to those found in children with 22q11.2DS.9 Also, the increased risk to
post-traumatic stress may not be specific for individuals with 22q11.2DS,
with prevalence rates in line with results reported for individuals with an
8
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