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

Abstract

Purpose of reviewWe describe here how such mechanisms shared by different genetic forms can give rise to motor performance dysfunctions with a clinical aspect of dystonia.Recent findingsThe 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.SummaryThe 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.

The Clinical Spectrum of ANO3—Report of a New Family and Literature Review

“…Since the advent of next‐generation sequencing (NGS), several genes have been associated with dystonic forms with a highly variable inheritance pattern, ranging from isolated forms of dystonia to complex dystonic syndromes 1 . Mutations in ANO3 are a rare cause of autosomal dominant isolated or combined dystonia, mainly presenting in adulthood with cranio‐cervical involvement, with or without dystonic tremor.…”