Among the neurodegenerative pathologies, EIF2B-related disorders are autosomal recessive leukodystrophies due to mutations in Eukaryotic Initiation Factor 2B genes (EIF2B). The Childhood Ataxia with Central Hypomyelination / Vanishing White Matter Syndrome (CACH/VWM) is the archetype form of those eIF2B-related disorders. It affects mainly the development and full maturation of the brain and is characterized by either a quick or a progressive evolution depending on the identified point mutation in the various EIF2B genes. Starting with hiPSCs derived from control and CACH patients (EIF2B5 R113H/R113H – a moderate phenotype) we generated cortical organoids that were analysed at the morphological level, by the detection of specific markers (PAX6, NESTIN, TBR2, MAP2, OLIG2, etc. among others and by transcriptomic analysis. It appears that the structure of the organoids is altered for those derived from mutant cells with a distribution and destructuring of the rosettes as well as a different distribution and expression levels of the main genes evaluated. The alteration of the gene expression profile is confirmed by transcircomic analysis which tends to establish a reduction in precursors and a delay in the maturation of these cells during the kinetics of organoid development In a complementary way, by creating dorsalized and ventralized cortical organoids, by marking them with fluorescent reporters (GFP and mKO), it is possible to evaluate their interaction within assembloids and to demonstrate the projection of the ventral structures in the dorsal part. This same model is applied and compared between control and CACH mutant cells. All of these data make it possible to highlight the impact of the EIF2B5 mutation in the development of the organoid and its very early alteration, from the appearance of precursors opening the way to consider CACH leukodystrophy as a developmental pathology.