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

Neurodevelopmental disorder caused by a truncating de novo variant of IRF2BPL

“…In 2018, Tran et al described 11 patients with IRF2BPL de novo truncating variants who were diagnosed with developmental epileptic encephalopathy [1]. In addition to this report, seven other studies found that IRF2BPL gene mutations were responsible for neurodevelopmental disorders [2][3][4][5][6][7][8]. To date, a total of 25 patients with IFR2BPL mutations have been reported worldwide, including in this study.…”

“…Many studies have recently found that the interferon regulatory factor 2 binding protein-like (IRF2BPL, MIM: 611720) gene with de novo truncating mutations is responsible for neurodevelopmental disorders [1][2][3][4][5][6][7][8]. Additionally, the mutations in IRF2BPL cause variable neurological phenotypes, such as neurodevelopmental regression, cerebellar ataxia, loss of motor skills, and intractable epilepsy.…”

IRF2BPL mutation causes nigrostriatal degeneration presenting with dystonia, spasticity and keratoconus

“…We also wish to highlight the association of IRF2BPL mutations with keratoconus. Indeed, one further case has also reported the presence of keratoconus in a patient with IRF2BPL mutation [3]. Although we cannot exclude that this might be a chance finding, we do believe that the occurrence of this uncommon ophthalmologic sign with progressive dystonia might further guide clinical diagnostic reasoning, pointing towards mutations in IRF2BPL.…”

“…Common clinical features in IRF2BPL mutation carriers include a variety of neurological symptoms from dystonia, ataxia, spasticity, dysarthria/anarthria, dysphagia and epilepsy to neurodevelopmental delay or regression [1][2][3][4]. We also wish to highlight the association of IRF2BPL mutations with keratoconus.…”

Do variants in IRF2BPL cause both neurological disorders and keratoconus 8?

“…1. Genomic location on chromosome 14 that includes the locus for keratoconus type 8 (KTCN8) as determined by Lišková et al [5], and the IRF2BL gene, in which four de novo truncating variants have been described in independent patients with neurological disease and keratoconus [1][2][3], reduced visual acuity [10], or retinal degeneration [7]. The highest LOD scores (3.58) in the keratoconus 8 families were obtained for rs1074501 and rs755212 [5].…”