{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:07:35Z","timestamp":1779084455105,"version":"3.51.4"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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":["Clinical Case Reports"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Walker\u2013Warburg syndrome (WWS) is a fatal autosomal recessive disorder characterized by brain and eye malformations, and prenatal diagnosis relies heavily on neuroimaging findings to guide targeted genetic screening. Here, we describe a distinctive second\u2010trimester fetal imaging pattern observed in two siblings. In\u00a0vivo and postmortem fetal magnetic resonance imaging demonstrated hydrocephalus, fused ventricles, hypoplastic cerebellar hemispheres, a small supraoccipital meningoencephalocele, and a recurrent hypoplastic \u2018Z\u2019\u2010shaped brainstem configuration. Whole\u2010exome sequencing identified a homozygous deletion in POMT1 (c.123\u201011_123\u20105del), confirmed by Sanger sequencing, and RNA sequencing suggested reduced expression of exon 3. Recognition of a \u2018Z\u2019\u2010shaped brainstem on fetal MRI should raise strong suspicion for WWS associated with POMT1 mutations, prompting integrated pathological assessment and genetic testing, particularly when there is a positive family history.<\/jats:p>","DOI":"10.1002\/ccr3.72716","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:40:39Z","timestamp":1779082839000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fetal Presentation of Walker\u2013Warburg Syndrome With a Novel\n                    <scp>POMT1<\/scp>\n                    Splice\u2010Altering Variant: Antenatal Imaging, Postmortem\n                    <scp>MRI<\/scp>\n                    , Autopsy, and Molecular Correlation"],"prefix":"10.1002","volume":"14","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiology, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Radiology, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis Center, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnosis Center, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[{"name":"Foshan Institute of Fetal Medicine, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0980-4139","authenticated-orcid":false,"given":"Fengying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, the Affiliated Foshan Women and Children Hospital Guangdong Medical University  Foshan Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3174\/ajnr.A1223","article-title":"Disorders of Cortical Formation: MR Imaging Features","volume":"30","author":"Abdel Razek A. A.","year":"2009","journal-title":"American Journal of Neuroradiology"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1086\/342975","article-title":"Mutations in the O\u2010Mannosyltransferase Gene POMT1 Give Rise to the Severe Neuronal Migration Disorder Walker\u2010Warburg Syndrome","volume":"71","author":"Beltran\u2010Valero de Bernabe D.","year":"2002","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1055\/s-0029-1224099","article-title":"POMT1\u2010Associated Walker\u2010Warburg Syndrome: A Disorder of Dendritic Development of Neocortical Neurons","volume":"40","author":"Judas M.","year":"2009","journal-title":"Neuropediatrics"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1080\/15513815.2022.2116620","article-title":"Fetal Presentation of Walker\u2010Warburg Syndrome With Compound Heterozygous POMT2 Missense Mutations","volume":"42","author":"Zago S.","year":"2023","journal-title":"Fetal and Pediatric Pathology"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1080\/02841850510021409","article-title":"Difficulties With Prenatal Diagnosis of the Walker\u2010Warburg Syndrome","volume":"46","author":"Low A. S.","year":"2005","journal-title":"Acta Radiologica"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/uog.15735","article-title":"Prenatal Diagnosis of Cobblestone Lissencephaly Associated With Walker\u2010Warburg Syndrome Based on a Specific Sonographic Pattern","volume":"47","author":"Lacalm A.","year":"2016","journal-title":"Ultrasound in Obstetrics & Gynecology"},{"key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000152795","article-title":"Heterogeneity of Congenital Retinal Non\u2010Attachment, Falciform Folds and Retinal Dysplasia. A Guide to Genetic Counselling","volume":"26","author":"Warburg M.","year":"1976","journal-title":"Human Heredity"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1212\/WNL.56.8.1059","article-title":"Clinical and Genetic Distinction Between Walker\u2010Warburg Syndrome and Muscle\u2010Eye\u2010Brain Disease","volume":"56","author":"Cormand B.","year":"2001","journal-title":"Neurology"},{"key":"e_1_2_12_10_1","article-title":"Ethnically Diverse Causes of Walker\u2010Warburg Syndrome (WWS): FCMD Mutations Are a More Common Cause of WWS Outside of the Middle East","volume":"29","author":"Manzini M. C.","year":"2008","journal-title":"Human Mutation"},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s10048-013-0367-8","article-title":"A Truncating Mutation in B3GNT1 Causes Severe Walker\u2010Warburg Syndrome","volume":"14","author":"Shaheen R.","year":"2013","journal-title":"Neurogenetics"},{"key":"e_1_2_12_12_1","first-page":"1688","article-title":"Fast MR Imaging of Fetal CNS Anomalies In Utero","volume":"21","author":"Simon E. M.","year":"2000","journal-title":"AJNR. American Journal of Neuroradiology"},{"key":"e_1_2_12_13_1","article-title":"Brain MR Imaging Findings in Children With Congenital Muscular Dystrophies","volume":"1","author":"Vercellino F.","year":"2022","journal-title":"International Journal of Clinical Images and Medical Reviews"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/humu.20561","article-title":"Molecular Heterogeneity in Fetal Forms of Type II Lissencephaly","volume":"28","author":"Bouchet C.","year":"2007","journal-title":"Human Mutation"},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/brain\/awr357","article-title":"Cobblestone Lissencephaly: Neuropathological Subtypes and Correlations With Genes of Dystroglycanopathies","volume":"135","author":"Devisme L.","year":"2012","journal-title":"Brain"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13023-019-1119-0","article-title":"Clinical Long\u2010Time Course, Novel Mutations and Genotype\u2010Phenotype Correlation in a Cohort of 27 Families With POMT1\u2010Related Disorders","volume":"14","author":"Geis T.","year":"2019","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.7863\/jum.2005.24.12.1697","article-title":"Magnetic Resonance Imaging of the Kinked Fetal Brain Stem: A Sign of Severe Dysgenesis","volume":"24","author":"Stroustrup Smith A.","year":"2005","journal-title":"Journal of Ultrasound in Medicine"},{"key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.ejpn.2018.06.011","article-title":"Prenatal Diagnosis of Brainstem Anomalies","volume":"22","author":"Haratz K. 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