Myoclonus-Dystonia in an Individual with a Mutation in the GRIN2A Gene

Abstract

Mutations in the GRIN2A gene are associated with epilepsy-aphasia spectrum disorders and developmental and epileptic encephalopathies. Associations have been linked with disorders, including autism spectrum disorder and Parkinson's disease. Recently, GRIN2A variants have been reported as a cause of movement disorders in individuals without epilepsy, suggesting that movement disorders should be highlighted as a genetic phenotype associated with pathogenic variants in GRIN2A. We present a case of a male with myoclonus dystonia and without epilepsy found on whole-exome sequencing to have a c.1880G > A; p.S627N variant in the GRIN2A gene. Our case contributes to the expanding phenotypic spectrum of GRIN2A-related disorders and highlights another genetic cause of the myoclonus-dystonia phenotype. GRIN2A should be considered a part of the differential diagnosis of myoclonus-dystonia in individuals with developmental delay without epilepsy.

Keywords

GRIN2A - pediatric movement disorders - hyperkinetic - myoclonus - dystonia

Publikationsverlauf

Eingereicht: 09. Juni 2022

Angenommen: 30. Juni 2022

Artikel online veröffentlicht:
15. September 2022

• References

• 1 Yuan H, Low CM, Moody OA, Jenkins A, Traynelis SF. Ionotropic GABA and glutamate receptor mutations and human neurologic diseases. Mol Pharmacol 2015; 88 (01) 203-217
• 2 Myers SJ, Yuan H, Kang JQ, Tan FCK, Traynelis SF, Low CM. Distinct roles of GRIN2A and GRIN2B variants in neurological conditions. F1000Res 2019 Nov 20;8: F1000. Fac Rev 1940;
• 3 Endele S, Rosenberger G, Geider K. et al. Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nat Genet 2010; 42 (11) 1021-1026
• 4 Carvill GL, Regan BM, Yendle SC. et al. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nat Genet 2013; 45 (09) 1073-1076
• 5 Lesca G, Rudolf G, Labalme A. et al. Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism. Epilepsia 2012; 53 (09) 1526-1538
• 6 Yuan H, Hansen KB, Zhang J. et al. Functional analysis of a de novo GRIN2A missense mutation associated with early-onset epileptic encephalopathy. Nat Commun 2014; 5: 3251
• 7 Myers KA, Scheffer IE. GRIN2A-related speech disorders and epilepsy. In: Adam MP, Mirzaa GM, Pagon RA. et al, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 2016: 1993-2022
• 8 Turner SJ, Mayes AK, Verhoeven A, Mandelstam SA, Morgan AT, Scheffer IE. GRIN2A: an aptly named gene for speech dysfunction. Neurology 2015; 84 (06) 586-593
• 9 Strehlow V, Heyne HO, Vlaskamp DRM. et al; GRIN2A study group. GRIN2A-related disorders: genotype and functional consequence predict phenotype. Brain 2019; 142 (01) 80-92
• 10 Lesca G, Rudolf G, Bruneau N. et al. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction. Nat Genet 2013; 45 (09) 1061-1066
• 11 Lemke JR, Lal D, Reinthaler EM. et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet 2013; 45 (09) 1067-1072
• 12 Ohba C, Shiina M, Tohyama J. et al. GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders. Epilepsia 2015; 56 (06) 841-848
• 13 Lemke JR, Geider K, Helbig KL. et al. Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy. Neurology 2016; 86 (23) 2171-2178
• 14 Platzer K, Lemke JR. GRIN2B-related neurodevelopmental disorder. In: Adam MP, Mirzaa GM, Pagon RA. et al, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 2018: 1993-2022
• 15 Platzer K, Lemke JR. GRIN1-related neurodevelopmental disorder. In: Adam MP, Mirzaa GM, Pagon RA. et al, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 2019: 1993-2022
• 16 Li J, Zhang J, Tang W. et al. De novo GRIN variants in NMDA receptor M2 channel pore-forming loop are associated with neurological diseases. Hum Mutat 2019; 40 (12) 2393-2413
• 17 Fernández-Marmiesse A, Kusumoto H, Rekarte S. et al. A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental disorder. Mov Disord 2018; 33 (06) 992-999
• 18 Nicotera AG, Calì F, Vinci M, Musumeci SA. GRIN2A: involvement in movement disorders and intellectual disability without seizures. Neurol Sci 2019; 40 (11) 2405-2406
• 19 Yoo Y, Jung J, Lee YN. et al. GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy. Ann Neurol 2017; 82 (03) 466-478