Genetic Dystonias: Update on Classification and New Genetic Discoveries

Ignacio Juan Keller Sarmiento, Niccolò Emanuele Mencacci*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


Purpose of Review: Since the advent of next-generation sequencing, the number of genes associated with dystonia has been growing exponentially. We provide here a comprehensive review of the latest genetic discoveries in the field of dystonia and discuss how the growing knowledge of biology underlying monogenic dystonias may influence and challenge current classification systems. Recent Findings: Pathogenic variants in genes without previously confirmed roles in human disease have been identified in subjects affected by isolated or combined dystonia (KMT2B, VPS16, HPCA, KCTD17, DNAJC12, SLC18A2) and complex dystonia (SQSTM1, IRF2BPL, YY1, VPS41). Importantly, the classical distinction between isolated and combined dystonias has become harder to sustain since many genes have been shown to determine multiple dystonic presentations (e.g., ANO3, GNAL, ADCY5, and ATP1A3). In addition, a growing number of genes initially linked to other neurological phenotypes, such as developmental delay, epilepsy, or ataxia, are now recognized to cause prominent dystonia, occasionally in an isolated fashion (e.g., GNAO1, GNB1, SCN8A, RHOBTB2, and COQ8A). Finally, emerging analyses suggest biological convergence of genes linked to different dystonic phenotypes. Summary: While our knowledge on the genetic basis of monogenic dystonias has tremendously grown, their clinical boundaries are becoming increasingly blurry. The current phenotype-based classification may not reflect the molecular structure of the disease, urging the need for new systems based on shared biological pathways among dystonia-linked genes.

Original languageEnglish (US)
Article number8
JournalCurrent neurology and neuroscience reports
Issue number3
StatePublished - Mar 2021


  • Classification
  • Dystonia
  • Molecular pathways
  • Next-generation sequencing

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology


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