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

De novo mutations in the interferon regulatory factor 2 binding protein-like (IRF2BPL) gene have been recently associated with different neurological phenotypes [ [1] Marcogliese P.C. Shashi V. Spillmann R.C. Stong N. Rosenfeld J.A. Koenig M.K. Martinez-Agosto J.A. Herzog M. Chen A.H. Dickson P.I. Lin H.J. Vera M.U. Salamon N. Graham Jr., J.M. Ortiz D. Infante E. Steyaert W. Dermaut B. Poppe B. Chung H.L. Zuo Z. Lee P.T. Kanca O. Xia F. Yang Y. Smith E.C. Jasien J. Kansagra S. Spiridigliozzi G. El-Dairi M. Lark R. Riley K. Koeberl D.D. Golden-Grant K. Program for Undiagnosed D. Undiagnosed Diseases N. Yamamoto S. Wangler M.F. Mirzaa G. Hemelsoet D. Lee B. Nelson S.F. Goldstein D.B. Bellen H.J. Pena L.D.M. IRF2BPL is associated with neurological phenotypes. Am. J. Hum. Genet. 2018; 103: 245-260 Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar , [2] Tran Mau-Them F. Guibaud L. Duplomb L. Keren B. Lindstrom K. Marey I. Mochel F. van den Boogaard M.J. Oegema R. Nava C. Masurel A. Jouan T. Jansen F.E. Au M. Chen A.H. Cho M. Duffourd Y. Lozier E. Konovalov F. Sharkov A. Korostelev S. Urteaga B. Dickson P. Vera M. Martínez-Agosto J.A. Begemann A. Zweier M. Schmitt-Mechelke T. Rauch A. Philippe C. van Gassen K. Nelson S. Graham Jr., J.M. Friedman J. Faivre L. Lin H.J. Thauvin-Robinet C. Vitobello A. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. Genet. Med. 2019; 21: 1008-1014 Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar ]. Clinical features include neurodevelopmental regression or speech and motor developmental delay, seizures, hypotonia, coordination difficulties, dystonia and pyramidal signs. So far, dopaminergic deficiency has not been described in IRF2BPL mutation carriers. We report a novel IRF2BPL mutation in a patient presenting with dystonia, spasticity and keratoconus, as well as pathologic dopamine transporter imaging.