{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:56:00Z","timestamp":1789516560666,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures","award":["163\/8\/10.01.2023"],"award-info":[{"award-number":["163\/8\/10.01.2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G&gt;A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. Methods: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. Results: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M\/F: 16\/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs\u2019 involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. Conclusions: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.<\/jats:p>","DOI":"10.3390\/biom14030270","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T10:47:30Z","timestamp":1708685250000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characteristics of Developmental and Epileptic Encephalopathy Associated with PACS2 p.Glu209Lys Pathogenic Variant\u2014Our Experience and Systematic Review of the Literature"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-4926","authenticated-orcid":false,"given":"Adina","family":"Stoian","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Bajko","sequence":"additional","affiliation":[{"name":"Department of Neurology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodica","family":"B\u0103la\u0219a","sequence":"additional","affiliation":[{"name":"Department of Neurology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8055-1739","authenticated-orcid":false,"given":"Sebastian","family":"Andone","sequence":"additional","affiliation":[{"name":"Department of Neurology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6297-0378","authenticated-orcid":false,"given":"Mircea","family":"Stoian","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Ormeni\u0219an","sequence":"additional","affiliation":[{"name":"1st Neurology Clinic, Mures County Emergency Hospital, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8056-1339","authenticated-orcid":false,"given":"Carmen","family":"Muntean","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-524X","authenticated-orcid":false,"given":"Claudia","family":"B\u0103nescu","sequence":"additional","affiliation":[{"name":"Department of Genetics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/cge.13516","article-title":"Expanding the clinical spectrum associated with PACS2 mutations","volume":"95","author":"Dentici","year":"2019","journal-title":"Clin. 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