Pediatric Genetic Dystonias: Current Diagnostic Approaches and Treatment Options

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.

Keywords: DYT1; chorea; dystonia–parkinsonism; movement disorder; pediatric dystonia.

Figure 1

Simplified diagram of the pathophysiological mechanisms underlying dystonia. The motor cortex controls voluntary movement and receives excitatory and inhibitory inputs from the thalamus, cerebellum, brainstem, and spinal cord. The basal ganglia play a central regulatory role in movement initiation through opposing pathways: the direct pathway promotes motor activity, while the indirect pathway suppresses it. An imbalance between excitatory and inhibitory signals within these circuits has been proposed as a key mechanism underlying dystonia. In addition, alterations in dopaminergic pathways have been shown to impact this balance, as evidenced by genetic variants affecting dopamine signaling and the clinical response observed in dopa-responsive dystonias. More recent evidence suggests that abnormal spatial and temporal activity within the direct pathway, particularly involving the globus pallidus internus (GPi) and substantia nigra pars reticulata (SNpr), may contribute to dystonia pathophysiology. The cerebellum has also been implicated, with disruptions in the cerebello–thalamo–cortical pathway and deficits in motor learning processes. Altered spatial and temporal discrimination of sensory stimuli appears to further contribute to dystonia onset, as highlighted by the presence of sensory tricks that temporarily relieve symptoms. This supports the hypothesis of a defective sensory gating mechanism, which normally regulates and adjusts motor responses to peripheral sensory inputs, enabling appropriate compensatory movements. Finally, disrupted neural plasticity, especially within inhibitory circuits descending from the brainstem and spinal cord, has been suggested as an additional mechanism contributing to the development of dystonia. Excitatory pathways are shown in green, inhibitory pathways in blue, and alterations leading to dystonia in red [11].