Page 34 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 2
Methods
The study protocol was published in the PROSPERO International Register
for Systematic Reviews (CRD42020191035). We made a few minor
amendments to the initial protocol, including the addition of two co-authors,
a repeated search, and inclusion of non-rare GNDs (e.g., Down syndrome).
We followed the Preferred Reporting Items for Systematic Reviews and
Meta-Analysis Protocol (PRISMA).10
Search strategy and selection
We performed a comprehensive literature search in PubMed and Embase
on June 15, 2021 (see the Supporting Information Supplementary Methods
and Supplementary Figure S1). We used the Human Phenotype Ontology
(HPO; https://hpo.jax.org/) term “neurodevelopmental abnormality”
(HP:0012759) for GNDs, in combination with database-specific subheadings
and text words for “Parkinson’s disease/parkinsonism”.11 Two reviewers
independently screened titles and abstracts for eligibility. Relevant records
were screened against selection criteria for inclusion based on full-text. In
case of uncertainty, two other reviewers were consulted. Discrepancies
were discussed until consensus was reached.
We included all reports on patients who met the inclusion criteria for a
neurodevelopmental disorder (i.e., listed in the HPO as “neurodevelopmental”
and/or representing patients showing a deviation from normal of the
neurological development in childhood, including any or all aspects of
the development of personal, social, motor, and cognitive abilities, in
the presence of a disease-causing genetic variant) and parkinsonism
(bradykinesia in combination with either rigidity, rest tremor or both),12 or
who were likely to have Parkinson’s disease, operationalized as a clear
beneficial response to levodopa, reduced dopamine transporter binding
with dopaminergic imaging and/or neuropathological hallmarks of
Parkinson’s disease. We considered hypokinesia, akinesia, and hypomimia
equal to bradykinesia if parkinsonism was diagnosed, in case bradykinesia
was not explicitly noted. We excluded: 1) reports on patients with uncertain
genetic etiology; i.e., not molecularly confirmed or according to standard
clinical diagnostic criteria, 2) ultra-rare genetic conditions with less than
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