{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:46:37Z","timestamp":1785836797761,"version":"3.56.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100030845","name":"IRCCS Fondazione Stella Maris","doi-asserted-by":"publisher","award":["RC 2022"],"award-info":[{"award-number":["RC 2022"]}],"id":[{"id":"10.13039\/100030845","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Heterozygous variants in the AHDC1 gene are associated with Xia Gibbs Syndrome (XGS), a genetic disorder with a highly variable phenotype. Cognitive impairment, motor delay, language delay, neonatal hypotonia, and sleep apnea are considered \u201ccardinal\u201d signs of the disease. In a multicenter cross\u2010sectional study, we analyzed the genetic, epileptological, behavioral, and neuroradiological features of 15 patients with XGS harboring heterozygous variants in AHDC1. The phenotype of our patient cohort is almost overlapping with that already reported in the literature. Seizures begin between 2 and 9\u2009years, while EEG is generally characterized by normal background activity with paroxysmal abnormalities in the posterior areas increased by sleep. We systematically analyzed brain imaging findings as the most frequent brain alteration: the thinning of the corpus callosum, followed by posterior fossa malformation and lateral ventricle morphology abnormalities. Regarding psychiatric disorders, we observed neurodevelopmental disorders such as ID, language disorders, Autism spectrum disorders (ASD), and ADHD in preschoolers, followed by a prevalence of externalizing problems during childhood and adolescence. Our study showed that epilepsy and brain anomalies are very common among XGS individuals. MRI changes are nonspecific, but their association with other clinical features of the syndrome can guide early diagnosis. EEG abnormalities are present in all epileptic patients in the temporal\u2010occipital regions with the same characteristics, so we could hypothesize that these abnormalities could represent a recognizable EEG pattern of XGS. Behavioral disorders represent an important problem, and longitudinal evaluations are needed to improve the classification of the psychopathological spectrum in XGS.<\/jats:p>","DOI":"10.1002\/ajmg.a.70163","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:12:56Z","timestamp":1777551176000},"page":"2067-2079","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical, Behavioral and Neuroradiological Phenotype in an Italian Cohort of Patients With Xia Gibbs Syndrome: A Multicenter Cross\u2010Sectional Study and Systematic Literature Review"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-9378","authenticated-orcid":false,"given":"Giulia","family":"Cinelli","sequence":"first","affiliation":[{"name":"Post Graduate School of Pediatrics, Department of Medical and Surgical Sciences of the Mothers, Children and Adults University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Della Vecchia","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA) University of Florence  Florence Italy"},{"name":"Neuroscience Department IRCCS Stella Maris Foundation  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2466-3357","authenticated-orcid":false,"given":"Patrizia","family":"Bergonzini","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences of the Mothers, Children and Adults University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Caramaschi","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences of the Mothers, Children and Adults University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Spezia","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences of the Mothers, Children and Adults University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Parenti","sequence":"additional","affiliation":[{"name":"Neurology, Section of Neurophysiology, Department of Biomedical, Metabolic and Neuroscience University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Filomena","family":"Madeo","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences of the Mothers, Children and Adults University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0288-8990","authenticated-orcid":false,"given":"Laura","family":"Lucaccioni","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Medical and Surgical Sciences of the Mothers, Children and Adults University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cavalleri","family":"Francesca","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology University Hospital of Modena  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Pugliese","sequence":"additional","affiliation":[{"name":"Psychology Unit, Women's and Children's Health Department University Hospital of Modena  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Raviglione","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit U.O.N.P.I.A ASST\u2013Rhodense  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Colonna","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit U.O.N.P.I.A ASST\u2013Rhodense  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8947-5990","authenticated-orcid":false,"given":"Olga","family":"Calabrese","sequence":"additional","affiliation":[{"name":"SSD Medical Genetics, Mother and Child Department University Hospital of Modena  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Stanghellini","sequence":"additional","affiliation":[{"name":"SSD Medical Genetics, Mother and Child Department University Hospital of Modena  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmen","family":"Marongiu","sequence":"additional","affiliation":[{"name":"Orthopaedics and 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-7872","authenticated-orcid":false,"given":"Lorenzo","family":"Iughetti","sequence":"additional","affiliation":[{"name":"Post Graduate School of Pediatrics, Department of Medical and Surgical Sciences of the Mothers, Children and Adults University of Modena and Reggio Emilia  Modena Italy"},{"name":"Pediatric Unit, Department of Medical and Surgical Sciences of the Mothers, Children and Adults University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010025\u201002765\u20107"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000505843"},{"key":"e_1_2_10_4_1","first-page":"1993","volume-title":"GeneReviews\u00ae [Internet]","author":"Chander 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