The apparent paradox of phenotypic diversity and shared mechanisms across dystonia syndromes

Purpose of review We describe here how such mechanisms shared by different genetic forms can give rise to motor performance dysfunctions with a clinical aspect of dystonia. Recent findings The continuing discoveries of genetic causes for dystonia syndromes are transforming our view of these disorders. They share unexpectedly common underlying mechanisms, including dysregulation in neurotransmitter signaling, gene transcription, and quality control machinery. The field has further expanded to include forms recently associated with endolysosomal dysfunction. The discovery of biological pathways shared between different monogenic dystonias is an important conceptual advance in the understanding of the underlying mechanisms, with a significant impact on the pathophysiological understanding of clinical phenomenology. The functional relationship between dystonia genes could revolutionize current dystonia classification systems, classifying patients with different monogenic forms based on common pathways. The most promising effect of these advances is on future mechanism-based therapeutic approaches.

Automated summary

The genetic causes of dystonia share common underlying mechanisms, including dysregulation in neurotransmitter signaling, gene transcription, and quality control machinery. Recent findings also include forms associated with endolysosomal dysfunction. Discovering these shared biological pathways is an important breakthrough in understanding the underlying mechanisms and clinical phenomenology of dystonia.