{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T01:52:46Z","timestamp":1781488366531,"version":"3.54.1"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Capillary\u00a0malformation\u2013arteriovenous malformation syndrome is a rare spectrum of vascular anomalies characterized by capillary malformations and high-flow vascular malformations, caused by loss-of-function mutations in the RASA1 and\/or EPHB4 genes. These mutations disrupt vascular differentiation and lead to complex malformations involving the brain, skin, and systemic vasculature. Since the first description in 2003, more than 200 cases have been reported, but intracranial arteriovenous shunts during the neonatal period remain extremely rare, as well as reports of the dual mutation RASA1 + EPHB4 or the immunological impact of the EPHB4 mutation. We report three cases of neonates presenting with early-onset high-flow shunts, each exhibiting a distinct genetic signature: CM-AVM1 (RASA1 mutation), CM-AVM2 (EPHB4 mutation), and dual variant (combined EPHB4 and RASA1 mutations). We analyzed and compared the clinical evolution, Doppler ultrasound trends, EEG, MRI and genetic data to highlight the distinct genotype\u2013phenotype spectrum. Early multimodal hemodynamic evaluation of neonates with CM-AVM allows the identification and optimum management of life-threatening shunts at the earliest possible stage.<\/jats:p>","DOI":"10.3390\/life16061001","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:44:58Z","timestamp":1781484298000},"page":"1001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Capillary Malformation\u2013Arteriovenous Malformation Syndrome Associated with RASA1 and EPHB4 Mutations: Comparative Case Series and Narrative Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2215-1631","authenticated-orcid":false,"given":"Carmina","family":"Nedelcu","sequence":"first","affiliation":[{"name":"Neonatal Intensive Care Unit, \u201cM.S. Curie\u201d Children\u2019s Hospital, Constantin Brancoveanu Boulevard, No. 20, 4th District, 041451 Bucharest, Romania"},{"name":"Department of Neonatal Intensive Care, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Doctoral School, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7778-0477","authenticated-orcid":false,"given":"Catalin","family":"Cirstoveanu","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, \u201cM.S. Curie\u201d Children\u2019s Hospital, Constantin Brancoveanu Boulevard, No. 20, 4th District, 041451 Bucharest, Romania"},{"name":"Department of Neonatal Intensive Care, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3824-1489","authenticated-orcid":false,"given":"Cristina","family":"Filip","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, \u201cM.S. Curie\u201d Children\u2019s Hospital, Constantin Brancoveanu Boulevard, No. 20, 4th District, 041451 Bucharest, Romania"},{"name":"Department of Pediatrics, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxandra Ioana","family":"Stefan","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, \u201cM.S. Curie\u201d Children\u2019s Hospital, Constantin Brancoveanu Boulevard, No. 20, 4th District, 041451 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Mihaela","family":"Bizubac","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, \u201cM.S. Curie\u201d Children\u2019s Hospital, Constantin Brancoveanu Boulevard, No. 20, 4th District, 041451 Bucharest, Romania"},{"name":"Department of Neonatal Intensive Care, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Carmen","family":"Heriseanu","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, \u201cM.S. Curie\u201d Children\u2019s Hospital, Constantin Brancoveanu Boulevard, No. 20, 4th District, 041451 Bucharest, Romania"},{"name":"Department of Neonatal Intensive Care, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai C. T.","family":"Dimitriu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cSf. Pantelimon\u201d Emergency Hospital, Carol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4974-8661","authenticated-orcid":false,"given":"Nicolae Sebastian","family":"Ionescu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Orthopedics, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Romanian Academy of Medical Sciences, 030167 Bucharest, Romania"},{"name":"Romanian Academy of Scientists, 030167 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Axente","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, \u201cM.S. Curie\u201d Children\u2019s Hospital, Constantin Brancoveanu Boulevard, No. 20, 4th District, 041451 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1086\/379793","article-title":"Capillary Malformation-Arteriovenous Malformation, a New Clinical and Genetic Disorder Caused by RASA1 Mutations","volume":"73","author":"Eerola","year":"2003","journal-title":"Am. J. Hum. 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