Objective: To investigate the genetic etiology of pediatric hyperkinetic movement disorders (PMDs), characterize their associated phenotypes, comorbidities, and neuroimaging findings, and evaluate the impact of genetic diagnosis on treatment strategies.

Background: PMDs in children encompass a heterogeneous group of neurological conditions marked by abnormal tone, posture, or involuntary movements. Hyperkinetic PMDs with suspected genetic origins present significant diagnostic challenges due to phenotypic overlap and variable expressivity.

Method: This retrospective, observational study analyzed medical records of pediatric patients (0–18 years) diagnosed with hyperkinetic PMDs at the Movement Disorder Unit of Hospital Sant Joan de Déu, Barcelona, from 2020 to 2023. Inclusion criteria comprised clinical diagnoses of chorea, dystonia, or myoclonus with a suspected genetic basis. Phenotypic characterization was performed using clinical data, neuroimaging studies, and video documentation. Genetic testing included targeted panels, WES, WGS, and arrayCGH, with variant interpretation based on international guidelines.

Results: Among 712 patients initially screened, 62 met the inclusion criteria (mean age ± SD: 8.6 ± 4.7 years; range: 6 months–18 years). A definitive genetic diagnosis was established in 40%, with pathogenic variants identified in genes such as GNAO1, ATP1A3, and ADCY5. Phenotypic variability was notable, with overlapping clinical features across different genetic etiologies. Neuroimaging abnormalities, primarily affecting the basal ganglia, were observed in 22%. Comorbidities such as intellectual disability and epilepsy were prevalent. NGS and WES outperformed conventional methods, such as array-CGH, in diagnostic yield. Genetic findings influenced treatment modifications in 80% of cases, guiding targeted pharmacological and non-pharmacological interventions.

Conclusion: This study underscores the clinical and genetic heterogeneity of pediatric hyperkinetic PMDs, reinforcing the importance of advanced molecular diagnostics in achieving accurate diagnoses. A precise genetic diagnosis enables personalized treatment approaches, potentially improving clinical outcomes. Future research should focus on expanding genotype-phenotype correlations, identifying novel monogenic disorders, and developing targeted molecular therapies to optimize patient care.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-and-clinical-spectrum-of-pediatric-hyperkinetic-movement-disorders-in-a-spanish-tertiary-center/