Developmental and Epileptic Encephalopathy Produced by the ATP1A2 Mutation

A rare case of a developmental encephalopathy with epilepsy (DEE) caused by the previously described de novo missense mutation p.Arg908Gln in the ATP1A2 gene is described: DEE98. The female patient, first examined at age 11 months, had microcephaly, severe psychomotor retardation, strabismus, and spastic paraparesis, along with DEE98-atypical pachypolymicrogyria on MRI. Epilepsy with polymorphic seizures, followed by remission for nine months and recurrence of seizures, began at age 15 months. DEE98 was diagnosed at age two years nine months by high-throughput exome sequencing followed by family trio Sanger sequencing. Another finding from high-throughput exome sequencing were two previously undescribed heterozygous variants of uncertain pathogenicity in the SPART gene, which causes autosomal recessive spastic paraplegia type 20 (SPG20); Sanger sequencing confirmed the trans position of the variants; the clinical feature common to typical SPG20 was early spastic paraparesis with contractures, though other symptoms did not match. Given the phenotypic diversity of SPG20 and the possibility that the patient had a combination of two independent diseases, an additional study of the pathogenicity of SPART variants was conducted at the mRNA level: pathogenicity was not confirmed and there were no grounds for diagnosis of SPG20.