A de novo pathogenic variant in DHX30 gene in a fetus with isolated dysgenesis of the corpus callosum

A 36 years old woman in her first pregnancy was referred at 24w3d for a dedicated neurosonographic examination due to a suspected short corpus callosum (CC). The examination depicted a dysgenetic CC with asymmetric thickness at the level of the body in coronal views, very thin in the midline and thicker in both sides, suggesting bilateral formation of Probst bundles. The BPD, HC, and transverse cerebellar diameters were in the normal low range without associated growth restriction. Associated anomalies were not detected in the brain or other organs. Following genetic consultation and a normal CMA, trio exome sequencing was performed and a de novo missense pathogenic mutation c.2353 C > T in the DHX30 gene was detected. This variant has been previously reported in children and adults, mostly with a severe phenotype including neurodevelopmental disorder with variable motor and language impairment, but also mild phenotypes have been reported. MRI describes delayed myelination, ventriculomegaly, and cortical and cerebellar atrophy as imaging features in affected patients. This is the first prenatal report of a DHX30‐associated neurodevelopmental disorder in which the fetus presents with isolated callosal dysgenesis, stressing the importance of exome sequencing in fetuses with this condition, as far as it is phenotypic presentation of numerous syndromes with different outcomes. Key points What is already known about this topic? Variants in DHX30 were described in individuals with two distinct phenotypes, a severe and a mild one. The severe phenotype includes intellectual disability, developmental delay, speech impairment, gait abnormalities and autism spectrum disorder. Most variants result in severe phenotypic manifestations and brain MRI features include brain atrophy, ventriculomegaly, and delayed myelination. Manifestations of this syndrome in the prenatal period have not been described. What does this study add? First description of phenotypic presentation of this rare autosomal dominant condition in fetuses. Non‐classical imaging presentation with isolated callosal dysgenesis probably with Probst bundles. Importance of exome sequencing evaluation in fetuses with callosal malformations, once the genotypic spectrum of associated anomalies is enormous and frequently the prenatal phenotype is far from the classic presentation of different syndromes.