Supra- and Infratentorial Atrophy with Cortical Blindness Caused by Mutations in SEPSECS: Case Report

Background/Purpose: Mutations in SEPSECS (encoding O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase) have been reported in 11 patients with pontocerebellar hypoplasia type II, progressive cerebellocerebral atrophy, and progressive encephalopathy. The phenotypic spectrum involves severe retardation, muscular hypotony, and early abnormalities of cerebellum, vermis, and cortex in MRI. A milder clinical course with slow progression of cerebellar atrophy has been described only recently.

Methods: Case report of an 18-year-old patient with initially marked delay in motor development and missing of contact behavior but notable advances in development up to his 10th year of life. At the age of 10 years, he quickly developed massive spasticity of all limbs and lost his previously intact ability to react to visual stimuli. Analysis of PEP1 and SEPSECS was conducted via Sanger sequencing. Panel analysis of candidate genes causative for neurodegeneration with brain iron accumulation (NBIA) was performed.

Results: Visual (VEP) and auditory (ABEP) evoked potentials were normal until his 4th year of life. When controlled at the age of 14 years, VEP could no longer be provoked. Control of cranial MRI—which had previously been unremarkable—now showed marked delay in myelinization and occipital supratentorial and also cerebellar atrophy. No mutations were found in PEP1. Two heterozygous, previously not reported, mutations in SEPSECS (c.1484_1485delCA [p.Thr495Ilefs*24] and c.277C>T [p.His93Tyr]) were identified.

Conclusion: We report a patient with severe retardation and late onset of supra- and infratentorial atrophy with cortical blindness and severe spasticity and previously undescribed mutations in SEPSECS, which we think to be causative considering the previously reported phenotypes of mutations in this gene.