ELP2 compound heterozygous variants associated with cortico-cerebellar atrophy, nodular heterotopia and epilepsy: Phenotype expansion and review of the literature.

Abstract The elongator complex is a highly conserved macromolecular assembly composed by 6 individual proteins (Elp 1–6) and it is essential for many cellular functions such as transcription elongation, histone acetylation and tRNA modification. ELP2 is the second major subunit and with Elp1 and Elp3 it shapes the catalytic core of this essential complex. ELP2 gene pathogenic variants have been reported to be associated with several neurodevelopmental disorders, such as intellectual disability, severe motor development delay with truncal hypotonia, spastic diplegia, choreoathetosis, short stature and neuropsychiatric problems. Here we report a case with heterozygous variants of the ELP2 gene associated with unpublished electro-clinical and neuroimaging features, such as abnormal eye movements, focal epilepsy, cortico-cerebellar atrophy and nodular cortical heterotopia on brain MRI. A possible phenotype-genotype correlation and the electro-clinical and neuroimaging phenotype expansion of ELP2 mutations are here discussed, together with considerations on involved cortico-cerebellar networks and a detailed review of the literature.