A de novo GRIA3 variant with complex hyperkinetic movement disorder in a girl with developmental delay and self-limited epilepsy

Missense variants in GRIA3 (glutamate ionotropic receptor AMPA type subunit 3), originally found in an X-linked intellectual disability syndrome in men [ [1] Wu Y. Arai A.C. Rumbaugh G. Srivastava A.K. Turner G. Hayashi T. Suzuki E. Jiang Y. Zhang L. Rodriguez J. Boyle J. Tarpey P. Raymond F.L. Nevelsteen J. Froyen G. Stratton M. Futreal A. Gecz J. Stevenson R. Schwartz C.E. Valle D. Huganir R.L. Wang T. Mutations in ionotropic AMPA receptor 3 alter channel properties and are associated with moderate cognitive impairment in humans. Proc. Natl. Acad. Sci. U. S. A. 2007; 104: 18163-18168 Crossref PubMed Scopus (84) Google Scholar ], have been later associated with an X-linked developmental and epileptic encephalopathy presenting with developmental delay, intellectual disability, seizures, behavioral problems, dysmorphic features, movement disorders and other manifestations such as distal muscle weakness, progressive sleep disturbance, or various orthopedic abnormalities (MIM: 300699). A growing number of affected female individuals is reported [ [2] Trivisano M. Santarone M.E. Micalizzi A. Ferretti A. Dentici M.L. Novelli A. Vigevano F. Specchio N. GRIA3 missense mutation is cause of an x-linked developmental and epileptic encephalopathy. Seizure. 2020; 83: 1-6 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar , [3] Martinez-Esteve Melnikova A. Pijuan J. Aparicio J. Ramírez A. Altisent-Huguet A. Vilanova-Adell A. Arzimanoglou A. Armstrong J. Palau F. Hoenicka J. San Antonio-Arce V. The p.Glu787Lys variant in the GRIA3 gene causes developmental and epileptic encephalopathy mimicking structural epilepsy in a female patient. Eur. J. Med. Genet. 2022; 65104442 Crossref PubMed Scopus (3) Google Scholar ]. Here we present a patient with a novel heterozygous missense de novo GRIA3 variant with intellectual deficits, self-limited epilepsy, axial hypotonia, spasticity, dystonia, choreiform movements and stereotypies.