{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T09:06:27Z","timestamp":1779527187423,"version":"3.53.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":142,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Pediatrics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ZBTB18<\/jats:italic>\n                      encodes a C2H2\u2010type zinc finger protein that acts as a transcriptional repressor and is essential for neurodevelopment. Variants in\n                      <jats:italic>ZBTB18<\/jats:italic>\n                      are associated with intellectual developmental disorder, autosomal dominant 22 (MRD22). Patients with MRD22 present with intellectual disability (ID), corpus callosum anomalies, hypotonia, microcephaly, growth problems, epilepsy, and variable facial dysmorphism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole exome sequencing (WES) was performed to identify the molecular etiology. Sanger sequencing was used to validate the variant. Clinical assessments were conducted using brain magnetic resonance imaging (MRI) and electroencephalogram (EEG).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our patient presented with sleep\u2010associated focal motor seizures, characterized by right\u2010sided clonic movements with impaired consciousness, accompanied by atypical absence seizures. She also exhibited global developmental delay, unexplained ankle hypertonia, and unique juvenile facies (characterized by a lack of complex emotional expression, a fixed gaze, and an overall immature facial gestalt). Video EEG demonstrated hypsarrhythmia, whereas brain MRI revealed no structural abnormalities at the age of 2.5 years. The patient received antiepileptic therapy, and seizure control was successfully achieved following perampanel treatment. A de novo\n                      <jats:italic>ZBTB18<\/jats:italic>\n                      variant (NM_205768.3: c.1474delA (p.Arg492Aspfs\u221711)) was identified in our patient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      To conclude, we report a de novo\n                      <jats:italic>ZBTB18<\/jats:italic>\n                      frameshift variant (NM_205768.3: c.1474delA (p.Arg492Aspfs\u221711)) in a female patient presenting with global developmental delay, epilepsy, ankle hypertonia, and unique juvenile facies. Notably, seizures were ultimately controlled with perampanel, which may provide a therapeutic insight for drug\u2010resistant epilepsy in MRD22. Our study expands the phenotypic and genetic spectrum of\n                      <jats:italic>ZBTB18<\/jats:italic>\n                      and provides novel insights into the clinical management of MRD22.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijpe\/7226289","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T08:24:17Z","timestamp":1779524657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of De Novo\n                    <i>ZBTB18<\/i>\n                    Variant in a Patient With Global Developmental Delay, Seizures, and Juvenile 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