{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:33:22Z","timestamp":1786361602662,"version":"build-2736575974"},"reference-count":16,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatr. Rep.","Pediatric Reports"],"abstract":"<jats:p>49,XXXXY syndrome (Fraccaro syndrome) is a rare sex chromosome pentasomy, historically considered a severe variant within the Klinefelter spectrum. It is characterized by intellectual disability, craniofacial dysmorphism, skeletal anomalies, hypogonadism, and congenital cardiac defects. Although neuroimaging abnormalities have increasingly been recognized in 49,XXXXY syndrome, neonatal diagnosis prompted primarily by ventriculomegaly remains rare. We report a neonate with prenatally detected ventriculomegaly in whom postnatal evaluation revealed cleft palate, congenital cardiac defects, bilateral cryptorchidism, and auditory dysfunction. Cranial ultrasonography and brain magnetic resonance imaging demonstrated bilateral ventriculomegaly with colpocephaly and a cavum vergae variant. Cytogenetic analysis confirmed the presence of a 49,XXXXY karyotype. This case highlights ventriculomegaly as a potential early diagnostic clue in 49,XXXXY syndrome and underscores the importance of chromosomal analysis in neonates presenting with structural brain abnormalities associated with multisystem anomalies. Early recognition is important for timely multidisciplinary surveillance and long-term endocrine follow-up.<\/jats:p>","DOI":"10.3390\/pediatric18030076","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:08:07Z","timestamp":1780510087000},"page":"76","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal Presentation of 49,XXXXY (Fraccaro) Syndrome with Ventriculomegaly: Expanding the Early Neuroimaging Phenotype"],"prefix":"10.3390","volume":"18","author":[{"given":"Gonca","family":"Vardar","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Acibadem Kartal Hospital, Istanbul 34873, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giray","family":"Girgin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Acibadem Kartal Hospital, Istanbul 34873, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emel","family":"Kabakoglu Unsur","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Acibadem Kartal Hospital, Istanbul 34873, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulcan","family":"Seymen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Acibadem Kartal Hospital, Istanbul 34873, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S0140-6736(60)91963-2","article-title":"A child with 49 chromosomes","volume":"2","author":"Fraccaro","year":"1960","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1111\/j.1651-2227.2011.02235.x","article-title":"48,XXYY, 48,XXXY and 49,XXXXY syndromes: Not just variants of Klinefelter syndrome","volume":"100","author":"Tartaglia","year":"2011","journal-title":"Acta Paediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1136\/jmg.35.5.420","article-title":"49,XXXXY: A distinct phenotype. 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Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1136\/jmg.8.2.220","article-title":"49,XXXXY chromosomal anomaly in a neonate","volume":"8","author":"Hayek","year":"1971","journal-title":"J. Med. Genet."},{"key":"ref_8","first-page":"858","article-title":"A rare case of ambiguous genitalia","volume":"48","author":"Ng","year":"2007","journal-title":"Singap. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"164","DOI":"10.4103\/0971-6866.73413","article-title":"A Sri Lankan child with 49,XXXXY syndrome","volume":"16","author":"Dissanayake","year":"2010","journal-title":"Indian J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.gene.2012.07.053","article-title":"Skeletal abnormalities of the upper limbs\u2014Neonatal diagnosis of 49,XXXXY syndrome","volume":"508","author":"Kidszun","year":"2012","journal-title":"Gene"},{"key":"ref_11","first-page":"181","article-title":"Neonatal diagnosis of 49, XXXXY syndrome","volume":"13","author":"Etemadi","year":"2015","journal-title":"Iran. J. Reprod. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.21037\/tp-23-23","article-title":"The timely diagnosis of 49, XXXXY with the combined detection of MLPA, karyotype, and QF-PCR in a newborn with multiple congenital malformations: A case report","volume":"12","author":"Tian","year":"2023","journal-title":"Transl. 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Case Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e13771","DOI":"10.1111\/and.13771","article-title":"Sexual and developmental aspects of 49, XXXXY Syndrome: A case report","volume":"52","author":"Hammami","year":"2020","journal-title":"Andrologia"}],"container-title":["Pediatric Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2036-7503\/18\/3\/76\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:06:14Z","timestamp":1786359974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2036-7503\/18\/3\/76"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":16,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["pediatric18030076"],"URL":"https:\/\/doi.org\/10.3390\/pediatric18030076","relation":{},"ISSN":["2036-7503"],"issn-type":[{"value":"2036-7503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]}}}