Abnormalities of the corpus callosum. Can prenatal imaging predict the genetic status? Correlations between imaging phenotype and genotype

• Published in: Prenatal diagnosis Vol. 43; no. 6; pp. 746 - 755
• Main Authors: Nguyen, Toan, Heide, Solveig, Guilbaud, Lucie, Valence, Stéphanie, Perre, Saskia Vande, Blondiaux, Eléonore, Keren, Boris, Quenum‐Miraillet, Geneviève, Jouannic, Jean‐Marie, Mandelbrot, Laurent, Picone, Olivier, Guet, Agnès, Tsatsaris, Vassilis, Milh, Mathieu, Girard, Nadine, Vincent, Marie, Nizon, Mathilde, Poirsier, Céline, Vivanti, Alexandre, Benachi, Alexandra, Portes, Vincent des, Guibaud, Laurent, Patat, Olivier, Spentchian, Myrtille, Frugère, Lisa, Héron, Delphine, Garel, Catherine
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2023
• Subjects: Abnormalities; Cerebellum; Cerebral hemispheres; Corpus callosum; Fetuses; Genotype & phenotype; Genotypes; Imaging; Lipoma; Phenotypes; TOR protein
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.6382

Objective Recent studies have evaluated prenatal exome sequencing (pES) for abnormalities of the corpus callosum (CC). The objective of this study was to compare imaging phenotype and genotype findings. Method This multicenter retrospective study included fetuses with abnormalities of the CC between 2018 and 2020 by ultrasound and/or MRI and for which pES was performed. Abnormalities of the CC were classified as complete (cACC) or partial (pACC) agenesis of the CC, short CC (sCC), callosal dysgenesis (CD), interhemispheric cyst (IHC), or pericallosal lipoma (PL), isolated or not. Only pathogenic (class 5) or likely pathogenic (class 4) (P/LP) variants were considered. Results 113 fetuses were included. pES identified P/LP variants for 3/29 isolated cACC, 3/19 isolated pACC, 0/10 isolated sCC, 5/10 isolated CD, 5/13 non‐isolated cACC, 3/6 non‐isolated pACC, 8/11 non‐isolated CD and 0/12 isolated IHC and PL. Associated cerebellar abnormalities were significantly associated with P/LP variants (OR = 7.312, p = 0.027). No correlation was found between phenotype and genotype, except for fetuses with a tubulinopathy and an MTOR pathogenic variant. Conclusions P/LP variants were more frequent in CD and in non‐isolated abnormalities of the CC. No such variants were detected for fetuses with isolated sCC, IHC and PL. Key points What is already known about this topic? The neurodevelopmental prognosis of abnormalities of the corpus callosum (CC) is mainly related to its etiology, and to the abnormalities appearing isolated or not from an imaging point of view. Genetic investigations, and recently prenatal exome sequencing combined with prenatal imaging play a pivotal role in the workup of abnormalities of the CC for prognostic evaluation. What does this study add? We provide a comprehensive description of the different types of abnormalities of the CC and correlate these phenotypes with the results of the genetic investigations, including prenatal exome sequencing.