{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T23:32:04Z","timestamp":1763076724776,"version":"3.45.0"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinocerebellar ataxia-21 (SCA21) is an autosomal dominant neurodegenerative disorder due to pathogenic variants of the TMEM240 gene. Its clinical presentation usually includes slowly progressive cerebellar ataxia, myoclonus-dystonia syndrome, cognitive impairment, and behavioral problems. Here, we reported the first patient with SCA21 presenting with a developmental and epileptic encephalopathy with seizure onset during late childhood, a seizure semeiology including atonic, clonic, myoclonic seizures, and absences with eyelid myoclonia and an EEG pattern characterized by diffuse spike and wave discharges. Epilepsy was associated with a progressive motor deterioration (the International Cooperative Ataxia Rating Scale-ICARS Total Ataxia score switched from 23\/100 to 35\/100 over a period of 2 years), a worsening of a preexisting tremor, and a disabling drowsiness. Nonverbal measure of intellectual functioning revealed a moderate intellectual disability (Leiter-R: brief IQ 40; fluid reasoning 52). The epileptogenic mechanisms involving TMEM240 might be correlated with disinhibition of excitotoxic networks due to the loss of Purkinje cells in the cerebellum, but also damage in neuronal bioenergetic pathways and synaptic vesicular trafficking within cortico-cerebellar and thalamo-cerebellar circuits.<\/jats:p>","DOI":"10.1055\/a-2646-2535","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T19:46:57Z","timestamp":1751485617000},"page":"404-407","source":"Crossref","is-referenced-by-count":0,"title":["Developmental and Epileptic Encephalopathy as a Novel Clinical Hallmark of SCA21"],"prefix":"10.1055","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7664-5807","authenticated-orcid":false,"given":"Mario","family":"Mastrangelo","sequence":"additional","affiliation":[{"name":"Dipartimento Materno-Infantile-Sapienza Universit\u00e0 di Roma, Rome, Italy"},{"name":"UOC di Neuropsichiatria Infantile-Dipartimento di Neuroscienze\/Salute Mentale-AOU Policlinico Umberto I-Roma, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomina","family":"Ricciardi","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Umane-Sapienza Universit\u00e0 di Roma, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Greco","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Umane-Sapienza Universit\u00e0 di Roma, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Bove","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Umane-Sapienza Universit\u00e0 di Roma, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Pollini","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Umane-Sapienza Universit\u00e0 di Roma, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Tolve","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa di Patologia Clinica, AOU Policlinico Umberto I-Roma, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Galosi","sequence":"additional","affiliation":[{"name":"UOC di Neuropsichiatria Infantile-Dipartimento di Neuroscienze\/Salute Mentale-AOU Policlinico Umberto I-Roma, Rome, Italy"},{"name":"Dipartimento di Neuroscienze, Umane-Sapienza Universit\u00e0 di Roma, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Pisani","sequence":"additional","affiliation":[{"name":"Dipartimento Materno-Infantile-Sapienza Universit\u00e0 di Roma, Rome, Italy"},{"name":"UOC di Neuropsichiatria Infantile-Dipartimento di Neuroscienze\/Salute Mentale-AOU Policlinico Umberto I-Roma, Rome, Italy"},{"name":"Dipartimento di Neuroscienze, Umane-Sapienza Universit\u00e0 di Roma, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1093\/brain\/awu202","article-title":"TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment","volume":"137","author":"J Delplanque","year":"2014","journal-title":"Brain"},{"issue":"12","key":"ref2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1212\/WNL.0000000000201015","article-title":"Pearls & Oy-sters: SCA21 due to TMEM240 variation presenting as myoclonus dystonia syndrome","volume":"99","author":"A Cherian","year":"2022","journal-title":"Neurology"},{"issue":"14","key":"ref3","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1177\/0883073820943488","article-title":"The neurodevelopmental and motor phenotype of SCA21 (ATX-TMEM240)","volume":"35","author":"E D Burdekin","year":"2020","journal-title":"J Child Neurol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5334\/tohm.858","article-title":"Myoclonus and dystonia as recurrent presenting features in patients with the SCA21-associated TMEM240 p.Pro170Leu variant","volume":"14","author":"U Sorrentino","year":"2024","journal-title":"Tremor Other Hyperkinet Mov (N Y)"},{"issue":"11","key":"ref5","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/mdc3.14220","article-title":"Dystonic tremor as main clinical manifestation of SCA21","volume":"11","author":"V Yahya","year":"2024","journal-title":"Mov Disord Clin Pract"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"e668","DOI":"10.1212\/NXG.0000000000000668","article-title":"On spinocerebellar ataxia 21 as a mimicker of cerebral palsy","volume":"8","author":"J van der Put","year":"2022","journal-title":"Neurol Genet"},{"issue":"08","key":"ref7","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1111\/ene.14868","article-title":"A next generation sequencing-based analysis of a large cohort of ataxic patients refines the clinical spectrum associated with spinocerebellar ataxia 21","volume":"28","author":"V Riso","year":"2021","journal-title":"Eur J Neurol"},{"issue":"08","key":"ref8","first-page":"e63","article-title":"Spinocerebellar ataxia type 21 (TMEM240) with tremor and dystonia","volume":"28","author":"C HF Camargo","year":"2021","journal-title":"Eur J Neurol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.parkreldis.2018.11.027","article-title":"The movement disorder spectrum of SCA21 (ATX-TMEM240): 3 novel families and systematic review of the literature","volume":"62","author":"A Trasch\u00fctz","year":"2019","journal-title":"Parkinsonism Relat Disord"},{"issue":"05","key":"ref10","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/epd2.20152","article-title":"ILAE genetics literacy series: progressive myoclonus epilepsies","volume":"25","author":"J M Cameron","year":"2023","journal-title":"Epileptic Disord"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1002\/hbm.25444","article-title":"Distinct effects of the basal ganglia and cerebellum on the thalamocortical pathway in idiopathic generalized epilepsy","volume":"42","author":"J Gong","year":"2021","journal-title":"Hum Brain Mapp"},{"issue":"04","key":"ref12","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1111\/epi.17881","article-title":"Patterns of subregional cerebellar atrophy across epilepsy syndromes: an ENIGMA-epilepsy study","volume":"65","author":"R Kerestes","year":"2024","journal-title":"Epilepsia"},{"issue":"03","key":"ref13","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s12311-020-01112-y","article-title":"The TMEM240 protein, mutated in SCA21, is expressed in Purkinje cells and synaptic terminals","volume":"19","author":"M Homa","year":"2020","journal-title":"Cerebellum"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.nbd.2018.08.022","article-title":"Lysosomal dysfunction and early glial activation are involved in the pathogenesis of spinocerebellar ataxia type 21 caused by mutant transmembrane protein 240","volume":"120","author":"T Seki","year":"2018","journal-title":"Neurobiol Dis"},{"issue":"32","key":"ref15","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.2174\/0929867330666221028150138","article-title":"A deep dive in the involvement of the cerebellum in epilepsy: a neuroanatomical and cellular approach","volume":"30","author":"C Rubio","year":"2023","journal-title":"Curr Med Chem"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2646-2535.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T23:31:09Z","timestamp":1763076669000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2646-2535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,2]]},"references-count":15,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2025,11,13]]},"published-print":{"date-parts":[[2025,12]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2646-2535","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"type":"print","value":"0174-304X"},{"type":"electronic","value":"1439-1899"}],"subject":[],"published-other":{"date-parts":[[2025,7,2]]},"published":{"date-parts":[[2025,7,2]]}}}