{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:51:59Z","timestamp":1785462719683,"version":"3.56.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mesencephalosynapsis is characterized by a failure of the dorsal brainstem colliculi to separate into distinct lateral masses (non-cleavage, a.k.a. \u201cfusion\u201d). It is linked to ventriculomegaly and aqueductal stenosis but other associations have not been systematically examined. We reviewed a large cohort of fetal hydrocephalus cases to explore associations of aqueductal stenosis, mesencephalosynapsis, and other pathologies. Among 115 cases of fetal obstructive hydrocephalus (15-41\u2009weeks gestation), mesencephalosynapsis was seen in 44 cases (38.3%). We graded the wide range of abnormal aqueductal histology; mesencephalosynapsis was associated with 67% of severe, 35% of mild, and 10% of borderline aqueductal pathologies. In 75% of cases, it was associated with other CNS anomalies, including rhombencephalosynapsis, holoprosencephaly, hemifacial microsomia, and amniotic rupture sequence. We also identified 2 cases of aqueductal stenosis associated with brainstem tegmental injury, probably ischemic in origin, without mesencephalosynapsis. Clinical and genetic associations of mesencephalosynapsis included diabetic embryopathy, amniotic rupture sequence, chromosomal abnormalities, and mutations in TBCD132, FRAS1, and NECTIN1. This is the largest review of the histology of fetal aqueductal stenosis to date. We conclude that mesencephalosynapsis points to a defect in embryonic brainstem patterning and may be isolated, associated with other malformations, and that it is found in heritable and non-heritable conditions.<\/jats:p>","DOI":"10.1093\/jnen\/nlae128","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T04:22:55Z","timestamp":1732335775000},"page":"195-209","source":"Crossref","is-referenced-by-count":5,"title":["Mesencephalosynapsis and aqueductal stenosis"],"prefix":"10.1093","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3304-4854","authenticated-orcid":false,"given":"Yael","family":"Fisher","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mount Sinai Hospital , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8647-6637","authenticated-orcid":false,"given":"Patrick","family":"Shannon","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mount Sinai Hospital , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orli","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mount Sinai Hospital , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chitayat","sequence":"additional","affiliation":[{"name":"The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto , Toronto, ON,","place":["Canada"]},{"name":"Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Chong","sequence":"additional","affiliation":[{"name":"The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Blaser","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging and Interventional Radiology, The Hospital for Sick Children, University of Toronto , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiri","family":"Shinar","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit, Ontario Fetal Center, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto , Toronto, ON,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"2025022107522203400_nlae128-B1","volume-title":"Observations on the Pathology of Hydrocephalus: H.M","author":"Russell","year":"1949"},{"key":"2025022107522203400_nlae128-B2","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-73697-1","volume-title":"Developmental Neuropathology","author":"Friede","year":"1989"},{"key":"2025022107522203400_nlae128-B3","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1177\/088307380101601211","article-title":"Neuropathologic research strategies in holoprosencephaly","volume":"16","author":"Sarnat","year":"2001","journal-title":"J Child Neurol"},{"key":"2025022107522203400_nlae128-B4","first-page":"151","article-title":"The middle interhemispheric variant of holoprosencephaly","volume":"23","author":"Simon","year":"2002","journal-title":"AJNR Am J 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