IRF2BPL mutations cause autosomal dominant dystonia with anarthria, slow saccades and seizures

In the ever-expanding spectrum of genetic dystonia syndromes, the presence of associated clinical signs can provide useful clues to guide diagnostic reasoning and inform treatment approaches. We have previously delineated the range of known etiologies associated with dystonia and anarthria/aphonia, and provided an algorithmic approach to reach diagnosis [ [1] Ganos C. Crowe B. Stamelou M. et al. The clinical syndrome of dystonia with anarthria/aphonia. Park. Relat. Disord. 2016; 24: 20-27 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar ]. Since then, mutations in the KMT2B gene have been added to this list and indeed, two of the patients we previously reported (cases 15 and 20)1 were subsequently found to harbor pathogenic mutations in this gene. Here, we wish to highlight a novel genetic etiology, namely mutations in the IRF2BPL gene, recently reported to cause a broad phenotypic range of neurological syndromes [ 2 Marcogliese P.C. Shashi V. Spillmann R.C. et al. IRF2BPL is associated with neurological phenotypes. Am. J. Hum. Genet. 2018; 103: 245-260 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar , 3 Skorvanek M. Dusek P. Rydzanicz M. et al. Neurodevelopmental Disorder Associated with IRF2BPL Gene Mutation: Expanding the Phenotype? Parkinsonism Relat Disord. 2019 Google Scholar , 4 Tran Mau-Them F. Guibaud L. Duplomb L. et al. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. Genet. Med. 2019; 21: 1008-1014 Crossref PubMed Scopus (15) Google Scholar ], with a particular focus on the syndromic association of dystonia with anarthria/aphonia.