{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:31:43Z","timestamp":1790011903388,"version":"4.0.1"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Child Neurology Society"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Adaptor protein complex 4\u2013associated hereditary spastic paraplegia (AP\u20104\u2010HSP) is a rare childhood\u2010onset neurogenetic disorder. With gene replacement therapies advancing, early\u2014potentially prenatal\u2014diagnosis holds significant clinical promise. We aimed to characterize fetal and perinatal brain MRI features of AP\u20104\u2010HSP to assess whether early imaging can prompt timely diagnosis, counseling, and interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective analysis, we reviewed prenatal imaging from 303 individuals with genetically confirmed AP\u20104\u2010HSP enrolled in the Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia (NCT04712812). Four patients (covering SPG47, SPG50, SPG52) with fetal, perinatal, or early postmortem imaging available were selected for detailed neuroradiologic evaluation. Systematic assessment documented several structural anomalies, correlated with genotype and clinical progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fetal imaging between 22 and 38 weeks' gestation revealed ventriculomegaly, corpus callosum hypoplasia, reduced periventricular white matter, and hippocampal under\u2010rotation across all subtypes. The SPG52 patient exhibited additional severe features, including gyral immaturity and pontine\/vermis hypoplasia. Postnatal follow\u2010up demonstrated progressive white matter volume reduction and delayed myelination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that fetal and perinatal brain MRI can detect early, consistent neurodevelopmental abnormalities in AP\u20104\u2010HSP, reinforcing its classification as both a neurodevelopmental and neurodegenerative disorder. Integration of prenatal neuroimaging with molecular diagnostics could enable earlier recognition, family counseling, and access to emerging gene therapies. These findings support the incorporation of fetal brain MRI into diagnostic protocols for suspected neurogenetic conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns3.70035","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T05:10:18Z","timestamp":1756962618000},"page":"226-231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fetal and Perinatal Brain MRI Findings in Adaptor Protein Complex 4\u2013Associated Hereditary Spastic Paraplegia"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5121-7686","authenticated-orcid":false,"given":"Alexandra K.","family":"Brooks","sequence":"first","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Quiroz","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Schierbaum","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian E.","family":"Alecu","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Bernardi","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-3436","authenticated-orcid":false,"given":"Amy","family":"Tam","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Rong","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Kasprian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image\u2010Guided Therapy Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Neuroradiology, Department of Radiology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0026-4714","authenticated-orcid":false,"given":"Darius","family":"Ebrahimi\u2010Fakhari","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"GeneReviews","author":"Alecu J.","year":"1993"},{"issue":"10","key":"e_1_2_9_3_1","first-page":"2929","article-title":"Defining the Clinical, Molecular and Imaging Spectrum of Adaptor Protein Complex 4\u2010Associated Hereditary Spastic Paraplegia","volume":"143","author":"Ebrahimi\u2010Fakhari 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