EEF2 encodes eukaryotic elongation factor 2 which catalyzes the elongation phase of protein translation. It is ubiquitously expressed and important for neuronal function. EEF2 was first associated with adult-onset spinocerebellar ataxia type 26 (SCA26). A novel neurodevelopmental disorder associated with de novo heterozygous variants in EEF2 has been described. Only 6 patients have been described in the literature thus far. A 9-year-old child with de novo novel missense variant is described here. EEF2-related neurodevelopmental disorder appears to be clinically recognizable. A nine-year-old male with autism spectrum disorder was referred for genetic evaluation. On examination, he had relative macrocephaly and frontal prominence. Whole exome sequencing revealed a de novo c.1225 C>T: p. (R409W) variant in exon 9 of the EEF2 gene (NM_001961.3). A comparison of clinical findings suggests that relative macrocephaly/macrocephaly and prominent forehead are consistent and easily identifiable clinical features of EEF2-related neurodevelopmental disorder. The clinical spectrum of this disorder is still emerging. EEF2-related neurodevelopmental disorder should be considered in a child with autism, developmental delays/intellectual disability, macrocephaly/relative macrocephaly, and frontal prominence.

In this article, we present an eight-year-old boy with developmental delay and cerebellar symptoms who was found to have a de novo eukaryotic elongation factor 2 (EEF2) mutation on genetic testing. Previously, pathogenic mutations in EEF2 have been associated with spinocerebellar ataxia 26. An extremely rare disorder, spinocerebellar ataxia type 26 (SCA26), has only been documented as an autosomal dominant, inherited, late-onset ataxia in one six-generation family of Norwegian descent. However, three pediatric patients with de novo EEF2 mutations were recently discovered, presenting with noncerebellar symptoms such as syndactyly, developmental delay, and behavioral issues. The patient of this study was found to have features similar to both adult patients with SCA26 as well as previous pediatric patients with de novo mutations.