Abnormalities of the corpus callosum. Can prenatal imaging predict the genetic status? Correlations between imaging phenotype and genotype
Toan Nguyen, Solveig Heide, Lucie Guilbaud, Stéphanie Valence, Saskia Vande Perre, Éléonore Blondiaux, Boris Keren, Geneviève Quenum‐Miraillet, Jean‐Marie Jouannic, Laurent Mandelbrot, Olivier Picone, Agnès Guët, Vassilis Tsatsaris, Mathieu Milh, Nadine Girard, Marie Vincent, Mathilde Nizon, Céline Poirsier, Alexandre Vivanti, Alexandra Benachi, Vincent des Portes, Laurent Guibaud, Olivier Patat, Myrtille Spentchian, Lisa Frugère, Delphine Héron, Cathérine Garel
Abstract
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.