Page 47 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Parkinsonism in GNDs
and treatment strategies, may reduce the burden on patients and their
families searching for answers (sometimes referred to as the “Diagnostic
Odyssey”), inform disease risks for family members, and help patients and
their families connecting with patient organizations for peer support.113 It
is important to realize that patients with GNDs may develop multiple early-
and late-onset comorbidities that require proactive attention depending on
the condition, that are typically not restricted to neurological problems, but
may involve all body systems.114, 115 Increasingly, expert clinics specializing
in specific GNDs are available, typically providing multidisciplinary care to
improve patient outcomes and quality of life.
Next generation sequencing techniques, such as whole exome sequencing
(WES), that may reveal a monogenic disorder,113 or chromosomal
microarray analysis, that identifies genome wide CNVs,116 may be used as
first line diagnostic tests. Certain features, including congenital anomalies
and ‘dysmorphic facial features’, may point to the presence of a specific
syndrome, but are absent in many patients. Here, it should also be noted
that conventional karyotyping will not detect CNVs or monogenic disorders
and that most currently available Parkinson’s disease genetic diagnostic
panels do typically not include GNDs. Therefore, an additional panel for
intellectual disability may need to be ordered. It should also be realized
that family history is often not a good predictor; many patients with a GND
have a de novo mutation. Selecting the most appropriate genetic test can
however be difficult; choosing the right test can require consultation with a
clinical geneticist. Limitations of most genetic tests include the high costs;
these tests are not readily available for many people, or inaccessible.
With recent advances in diagnosis and treatment of GNDs, targeted
disease-modifying therapies have become available for an increasing
number of patients diagnosed with a GND, i.e., for those with an inborn error
of metabolism or tuberous sclerosis complex.117-119 Early detection of such
disorders allows for timely interventions to prevent further brain damage
and/or disease progression. Prominent examples of treatable inborn errors
of metabolism in this review include phenylketonuria and other conditions
that lead to disruptions in monoaminergic neurotransmitter metabolism
(e.g., TH, and DNAJC12).117 These patients may have great benefit from
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