Pediatric Genetic Dystonias: Current Diagnostic Approaches and Treatment Options

TL;DR

This review discusses the diagnosis and treatment of genetic dystonias in children, emphasizing the importance of early detection and personalized care.

Contribution

The paper provides an updated overview of pediatric genetic dystonias, focusing on differential diagnosis and treatment strategies.

Findings

Over 250 genes are associated with pediatric dystonias, with TOR1A, SGCE, and KMT2B being the most frequently reported.

Whole-exome and whole-genome sequencing have improved early identification of causative genetic variants.

Symptomatic treatments and emerging gene therapies, like those for AADC deficiency, show promise in managing dystonias.

Abstract

Genetic dystonias are a heterogeneous group of movement disorders characterized by involuntary, sustained muscle contractions that cause repetitive movements and abnormal postures. Often beginning in childhood, they can significantly affect quality of life. Although individually rare, genetic causes are collectively relevant in pediatric dystonias, with over 250 associated genes. Among these, TOR1A, SGCE, and KMT2B are the most frequently reported in pediatric forms. Diagnosis is challenging due to the wide clinical and genetic variability. Recent advances in genetic testing, including whole-exome and whole-genome sequencing, have improved the early identification of causative variants. Functional data on selected mutations are helping to refine genotype–phenotype correlations. Management typically requires a multidisciplinary approach. Symptomatic treatments include anticholinergics, benzodiazepines, and botulinum toxin, while deep brain stimulation can be effective in refractory cases, especially in patients with TOR1A variants. Disease-modifying therapies are also emerging, such as gene therapy for AADC deficiency, highlighting the potential of precision medicine. This review provides an updated overview of pediatric genetic dystonias, with a focus on differential diagnosis and treatment strategies. Early and accurate diagnosis, together with personalized care, is key to improving outcomes in affected children.

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