Page 33 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Parkinsonism in GNDs
Introduction
While genetic brain disorders are traditionally dichotomized into
neurodevelopmental and neurodegenerative disorders, it is becoming
clear that some conditions are associated with both neurodevelopmental
problems and neurodegeneration,1 and there are indications for a shared
underlying genetic susceptibility.2, 3 Indeed, with advances in clinical genetic
testing for neurological disease and an increase in life expectancy due to
improved medical care, a growing number of genetic neurodevelopmental
disorders (GNDs) has been associated with the development of Parkinson’s
disease and other forms of parkinsonism.4-6
Although individually rare, research in GNDs may help to better understand
different pathophysiological mechanisms that are believed to play a role
in the development of parkinsonism. An analogy may be found in Down
syndrome that is associated with early-onset Alzheimer’s dementia.
Research in Down syndrome has provided important insights into dementia
etiology,7 and has facilitated research into disease-modifying treatments.8,
9 Genetic variants associated with GNDs are often identified in childhood,
before neurologic symptoms emerge, and long-term follow up of children
and adolescents with GNDs may increase knowledge on disease trajectories.
In addition to the potential to identify disease and/or mechanism-specific
treatment through animal models that are available for many genetic
conditions, recognition of GNDs associated with parkinsonism may
improve anticipatory care for patients with these GNDs. Thus, knowledge
about GNDs that may present with parkinsonism is important to optimize
clinical practice and further research.
In this systematic literature review, a comprehensive overview is provided
of studies that reported on parkinsonism in GNDs. We summarize findings
related to patient characteristics, parkinsonian features and proposed
disease mechanisms, and outline implications for clinical practice and
future research.
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