S Subramanian1, A Biswas2, C A P F Alves3, S V Sudhakar4, K V Shekdar5, P Krishnan2, M Shroff2, A Taranath6, F Arrigoni7, K A Aldinger8,9, R J Leventer10,11, W B Dobyns9,12, K Mankad4. 1. From the Division of Pediatric Radiology (S.S.), Department of Radiology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania subramanian.subramanian2@chp.edu. 2. Department of Diagnostic Imaging (A.B., P.K., M.S.), The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 3. Division of Neuroradiology (C.A.P.F.A.). 4. Department of Radiology (S.V.S., K.M.), Great Ormond Street Hospital, NHS Foundation Trust, London, UK. 5. Department of Radiology, and Department of Radiology (K.V.S.), Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 6. Department of Medical Imaging (A.T.), Women's and Children's Hospital, Adelaide, South Australia, Australia. 7. Neuroimaging Lab (F.A.), Scientific Institute, Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea, Bosisio Parini, Italy. 8. Department of Pediatrics (K.A.A.), University of Washington School of Medicine, Seattle, Washington. 9. Center for Integrative Brain Research (K.A.A., W.B.D.), Seattle Children's Research Institute, Seattle, Washington. 10. Department of Neurology (R.J.L.), Royal Children's Hospital and Murdoch Children's Research Institute, Parkville, Victoria, Australia. 11. Department of Pediatrics (R.J.L.), University of Melbourne, Melbourne, Victoria, Australia. 12. Division of Genetics and Metabolism (W.B.D.), Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Abstract
BACKGROUND AND PURPOSE: Pathogenic variants in the ACTA2 gene cause a distinctive arterial phenotype that has recently been described to be associated with brain malformation. Our objective was to further characterize gyral abnormalities in patients with ACTA2 pathogenic variants as per the 2020 consensus recommendations for the definition and classification of malformations of cortical development. MATERIALS AND METHODS: We performed a retrospective, multicentric review of patients with proved ACTA2 pathogenic variants, searching for the presence of malformations of cortical development. A consensus read was performed for all patients, and the type and location of cortical malformation were noted in each. The presence of the typical ACTA2 arterial phenotype as well as demographic and relevant clinical data was obtained. RESULTS: We included 13 patients with ACTA2 pathogenic variants (Arg179His mutation, n = 11, and Arg179Cys mutation, n = 2). Ninety-two percent (12/13) of patients had peri-Sylvian dysgyria, 77% (10/13) had frontal dysgyria, and 15% (2/13) had generalized dysgyria. The peri-Sylvian location was involved in all patients with dysgyria (12/12). All patients with dysgyria had a characteristic arterial phenotype described in ACTA2 pathogenic variants. One patient did not have dysgyria or the characteristic arterial phenotype. CONCLUSIONS: Dysgyria is common in patients with ACTA2 pathogenic variants, with a peri-Sylvian and frontal predominance, and was seen in all our patients who also had the typical ACTA2 arterial phenotype.
BACKGROUND AND PURPOSE: Pathogenic variants in the ACTA2 gene cause a distinctive arterial phenotype that has recently been described to be associated with brain malformation. Our objective was to further characterize gyral abnormalities in patients with ACTA2 pathogenic variants as per the 2020 consensus recommendations for the definition and classification of malformations of cortical development. MATERIALS AND METHODS: We performed a retrospective, multicentric review of patients with proved ACTA2 pathogenic variants, searching for the presence of malformations of cortical development. A consensus read was performed for all patients, and the type and location of cortical malformation were noted in each. The presence of the typical ACTA2 arterial phenotype as well as demographic and relevant clinical data was obtained. RESULTS: We included 13 patients with ACTA2 pathogenic variants (Arg179His mutation, n = 11, and Arg179Cys mutation, n = 2). Ninety-two percent (12/13) of patients had peri-Sylvian dysgyria, 77% (10/13) had frontal dysgyria, and 15% (2/13) had generalized dysgyria. The peri-Sylvian location was involved in all patients with dysgyria (12/12). All patients with dysgyria had a characteristic arterial phenotype described in ACTA2 pathogenic variants. One patient did not have dysgyria or the characteristic arterial phenotype. CONCLUSIONS: Dysgyria is common in patients with ACTA2 pathogenic variants, with a peri-Sylvian and frontal predominance, and was seen in all our patients who also had the typical ACTA2 arterial phenotype.
Authors: F D'Arco; C A Alves; C Raybaud; W K K Chong; G E Ishak; S Ramji; M Grima; A J Barkovich; V Ganesan Journal: AJNR Am J Neuroradiol Date: 2018-09-27 Impact factor: 3.825
Authors: M A Glukhova; A E Kabakov; M G Frid; O I Ornatsky; A M Belkin; D N Mukhin; A N Orekhov; V E Koteliansky; V N Smirnov Journal: Proc Natl Acad Sci U S A Date: 1988-12 Impact factor: 11.205
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Authors: Maria-Magdalena Georgescu; Marco da Cunha Pinho; Timothy E Richardson; Jose Torrealba; L Maximilian Buja; Dianna M Milewicz; Jack M Raisanen; Dennis K Burns Journal: Acta Neuropathol Commun Date: 2015-12-04 Impact factor: 7.801