{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:36:17Z","timestamp":1793644577757,"version":"4.5.1"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rho\u2010related BTB domain\u2010containing protein 2 (<jats:italic>RHOBTB2<\/jats:italic>) is a protein that interacts with cullin\u20103, a crucial E3 ubiquitin ligase for mitotic cell division. <jats:italic>RHOBTB2<\/jats:italic> has been linked to early infantile epileptic encephalopathy, autosomal dominant type 64 (OMIM618004), in 34 reported patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present a case series of seven patients with <jats:italic>RHOBTB2<\/jats:italic>\u2010related disorders (<jats:italic>RHOBTB2<\/jats:italic>\u2010RD), including a description of a novel heterozygous variant. We also reviewed previously published cases of <jats:italic>RHOBTB2<\/jats:italic>\u2010RD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The seven patients had ages ranging from 2\u2009years and 8\u2009months to 26\u2009years, and all had experienced seizures before the age of one (onset, 4\u201312\u2009months, median, 4\u2009months), including various types of seizures. All patients in this cohort also had a movement disorder (onset, 0.3\u201314\u2009years, median, 1.5\u2009years). Six of seven had a baseline movement disorder, and one of seven only had paroxysmal dystonia. Stereotypies were noted in four of six, choreodystonia in three of six, and ataxia in one case with multiple movement phenotypes at baseline. Paroxysmal movement disorders were observed in six of seven patients for whom carbamazepine or oxcarbazepine treatment was effective in controlling acute or paroxysmal movement disorders. Four patients had acute encephalopathic episodes at ages 4 (one patient) and 6 (three patients), which improved following treatment with methylprednisolone. Magnetic resonance imaging scans revealed transient fluid\u2010attenuated inversion recovery abnormalities during these episodes, as well as myelination delay, thin corpus callosum, and brain atrophy. One patient had a novel <jats:italic>RHOBTB2<\/jats:italic> variant (c.359G&gt;A\/p.Gly120Glu).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>RHOBTB2<\/jats:italic>\u2010RD is characterized by developmental delay or intellectual disability, early\u2010onset seizures, baseline movement disorders, acute or paroxysmal motor phenomena, acquired microcephaly, and episodes of acute encephalopathy. Early onsets of focal dystonia, acute encephalopathic episodes, episodes of tongue protrusion, or peripheral vasomotor disturbances are important diagnostic clues. Treatment with carbamazepine or oxcarbazepine was found to be effective in controlling acute or paroxysmal movement disorders. Our study highlights the clinical features and treatment response of <jats:italic>RHOBTB2<\/jats:italic>\u2010RD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mdc3.13880","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T06:25:36Z","timestamp":1694499936000},"page":"1671-1679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Exploring the Spectrum of <scp><i>RHOBTB2<\/i><\/scp> Variants Associated with Developmental Encephalopathy 64: A Case Series and Literature Review"],"prefix":"10.1002","volume":"10","author":[{"given":"Sonia","family":"de Pedro Baena","sequence":"first","affiliation":[{"name":"Pediatric Department Hospital Universitario Ram\u00f3n y Cajal  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sariego Jamardo","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department Hospital Universitario Marqu\u00e9s de Valdecilla  Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hospital Gregorio Mara\u00f1\u00f3n  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-0344","authenticated-orcid":false,"given":"Francisco Javier","family":"L\u00f3pez Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Neurology Department Complejo Hospitalario Universitario de Santiago de Compostela  Santiago Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-0686","authenticated-orcid":false,"given":"Roc\u00edo","family":"S\u00e1nchez Carpintero","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Unit. Paediatric Department University Clinic of Navarra  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-2828","authenticated-orcid":false,"given":"Alfredo","family":"Cerisola","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department Institut de Recerca, Hospital Sant Joan de D\u00e9u Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2539-4929","authenticated-orcid":false,"given":"M\u00f3nica","family":"Troncoso","sequence":"additional","affiliation":[{"name":"Centro de Referencia Nacional en Defectos Cong\u00e9nitos y Enfermedades Raras (CRENADECER) del Banco de Previsi\u00f3n Social (BPS), Uruguay; C\u00e1tedra de Neuropediatr\u00eda, Facultad de Medicina Universidad de la Rep\u00fablica  Montevideo 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