Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants.

We studied a family in which the first-born child, a girl, had developmental delay, facial dysmorphism, and agenesis of the corpus callosum (ACC). The subsequent pregnancy was interrupted as the fetus was found to be also affected by ACC. Both cases were heterozygous for two KDM5B variants predicting p (Ala635Thr) and p (Ser1155AlafsTer4) that were shown to be in trans. KDM5B variants have been previously associated with moderate to severe developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and dysmorphism in a few individuals, but the pathogenetic mechanisms are not clear yet as patients with both monoallelic and biallelic variants have been observed. Interestingly, one individual has previously been reported with ACC and severe ID in association with biallelic KDM5B variants. Together with the observations in this family, this suggests that agenesis of the corpus callosum may be part of the phenotypic spectrum associated with KDM5B variants and that the KDM5B gene should be included in gene panels to clarify the etiology of ACC both in the prenatal and postnatal setting.