{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:48:47Z","timestamp":1790380127370,"version":"4.1.0"},"reference-count":10,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Christina Capozzi Memorial Foundation","award":["Grant number N\/A"],"award-info":[{"award-number":["Grant number N\/A"]}]},{"name":"T.J. Reynolds Endowment Fund","award":["Grant number N\/A"],"award-info":[{"award-number":["Grant number N\/A"]}]},{"name":"Ansley's Heart Endowment Fund","award":["Grant number N\/A"],"award-info":[{"award-number":["Grant number N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Pulmonary vein stenosis (PVS) is a rare, frequently lethal disease with heterogeneous phenotypes and an unclear etiology. Limited studies have reported associations between PVS and congenital heart disease (CHD), chronic lung disease (CLD), and\/or prematurity; however, to date, there have been no studies that report detailed clinical syndromic phenotypes and the potential role of genetics in PVS. An existing registry of multivessel PVS patients seen at Boston Children\u2019s Hospital (BCH) was queried between August 2006 and January 2017 for all existing genetic testing data on these patients. PVS was defined as an intraluminal pulmonary venous obstruction in \u22652 vessels with mean pressure gradients &gt; 4 mmHg. One-hundred-and-fifty-seven patients (46% female, with a median age at PVS diagnosis of 3 months) formed the cohort. Seventy-one (45%) patients had available genetic testing information. Of the 71 patients, a likely genetic diagnosis was found in 23 (32%) patients: 13 (57%) were diagnosed with Trisomy 21 (T21), five (22%) with Smith\u2013Lemli\u2013Opitz Syndrome, five (22%) had other pathologic genetic disease, and 24 (33%) had variants of unknown significance. The majority of 13 patients with T21 and PVS had common atrioventricular canal (CAVC) (10, 77%) and all had severe pulmonary hypertension (PHTN), which led to their PVS diagnosis. In our study, PVS was associated with T21, the majority of whom also had CAVC and PHTN. Therefore, complete assessment of the pulmonary veins should be considered for all T21 patients, especially those with CAVC presenting with PHTN. Furthermore, prospective standardized genetic testing with detailed clinical phenotyping may prove informative about potential genetic etiologies of PVS.<\/jats:p>","DOI":"10.3390\/children8020128","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:49:26Z","timestamp":1613090966000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical Syndromic Phenotypes and the Potential Role of Genetics in Pulmonary Vein Stenosis"],"prefix":"10.3390","volume":"8","author":[{"given":"Abbas H.","family":"Zaidi","sequence":"first","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1060-1945","authenticated-orcid":false,"given":"David T.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"McEnaney","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3805-2191","authenticated-orcid":false,"given":"Christina","family":"Ireland","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberlee","family":"Gauvreau","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy J.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8043-894X","authenticated-orcid":false,"given":"Ming Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Pediatrics, Division of Genetics and Genomics, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1161\/CIRCULATIONAHA.106.646166","article-title":"Congenital and Acquired Pulmonary Vein Stenosis","volume":"115","author":"Latson","year":"2007","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1136\/hrt.2008.161356","article-title":"Pulmonary vein stenosis: The UK, Ireland and Sweden collaborative study","volume":"95","author":"Seale","year":"2009","journal-title":"Heart"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0002-9149(00)01022-5","article-title":"Mechanism of pulmonary vein stenosis in infants with normally connected veins","volume":"86","author":"Sadr","year":"2000","journal-title":"Am. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e656","DOI":"10.1542\/peds.2008-0075","article-title":"Pulmonary vein stenosis: Prematurity and associated conditions","volume":"122","author":"Drossner","year":"2008","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"F282","DOI":"10.1136\/archdischild-2013-304740","article-title":"Pulmonary vein stenosis and necrotising enterocolitis: Is there a possible link with necrotising enterocolitis?","volume":"99","author":"Heching","year":"2014","journal-title":"Arch. Dis. Child.-Fetal Neonatal Ed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1055\/s-0035-1571201","article-title":"Pulmonary Vein Stenosis in Neonates with Severe Bronchopulmonary Dysplasia","volume":"33","author":"Swier","year":"2016","journal-title":"Am. J. Perinatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/chd.12471","article-title":"Pulmonary vein stenosis in patients with Smith-Lemli-Opitz syndrome","volume":"12","author":"Prosnitz","year":"2017","journal-title":"Congenit. Heart Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E90","DOI":"10.1111\/chd.12088","article-title":"Pulmonary vein stenosis with Down syndrome: A rare and frequently fatal cause of pulmonary hypertension in infants and children","volume":"9","author":"Gowda","year":"2014","journal-title":"Congenit. Heart Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jpeds.2018.01.029","article-title":"Adjunct Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel Intraluminal Pediatric Pulmonary Vein Stenosis","volume":"198","author":"Callahan","year":"2018","journal-title":"J. Pediatrics"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Choi, C., Gauvreau, K., Levy, P., Callahan, R., Jenkins, K.J., and Chen, M. (2021). Longer Exposure to Left-to-Right Shunts Is a Risk Factor for Pulmonary Vein Stenosis in Patients with Trisomy 21. Children, 8.","DOI":"10.3390\/children8010019"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/2\/128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:22:27Z","timestamp":1760160147000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/2\/128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,10]]},"references-count":10,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["children8020128"],"URL":"https:\/\/doi.org\/10.3390\/children8020128","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,10]]}}}