Pontocerebellar hypoplasia type 2D and optic nerve atrophy further expand the spectrum associated with selenoprotein biosynthesis deficiency

Eur J Paediatr Neurol. 2016 May;20(3):483-8. doi: 10.1016/j.ejpn.2015.12.016. Epub 2016 Jan 11.


Background: The term Pontocerebellar hypoplasias collectively refers to a group of rare, heterogeneous and progressive disorders, which are frequently inherited in an autosomal recessive manner and usually have a prenatal onset. Mutations in the SEPSECS gene, leading to deficiency in selenoprotein biosynthesis, have been identified in recent times as the molecular etiology of different pre/perinatal onset neurological phenotypes, including cerebello-cerebral atrophy, Pontocerebellar hypoplasia type 2D and progressive encephalopathy with elevated lactate. These disorders share a similar spectrum of central (e.g., brain neurodegeneration with grey and white matter both involved) and peripheral (e.g., spasticity due to axonal neuropathy) nervous system impairment.

Case presentation: We hereby describe a 9-year-old boy with (i) a typical Pontocerebellar hypoplasia type 2D phenotype (e.g. profound mental retardation, spastic quadriplegia, ponto-cerebellar hypoplasia and progressive cerebral atrophy); (ii) optic nerve atrophy and (iii) mild secondary mitochondrial myopathy detected by muscle biopsy and respiratory chain enzyme analysis. We performed whole exome sequencing which identified a homozygous mutation of the SEPSECS gene (c.1001T > C), confirming the clinical suspect of Pontocerebellar hypoplasia type 2D.

Conclusion: This report further corroborates the notion of a potential secondary mitochondrial dysfunction in the context of selenoprotein biosynthesis deficiency and also adds optic nerve atrophy as a new potential clinical feature within the SEPSECS-associated clinical spectrum. These findings suggest the presence of a possible shared genetic etiology among similar clinical entities characterized by the combination of progressive cerebello-cerebral and optic nerve atrophy and also stress the biological importance of selenoproteins in the regulation of neuronal and metabolic homeostasis.

Keywords: Mitochondrial myopathy; Optic nerve atrophy; Pontocerebellar hypoplasia; SEPSECS; Selenoprotein biosynthesis deficiency.

Publication types

  • Case Reports

MeSH terms

  • Amino Acyl-tRNA Synthetases / genetics*
  • Atrophy
  • Cerebellar Diseases / complications
  • Cerebellar Diseases / diagnosis*
  • Cerebellar Diseases / genetics
  • Child
  • Humans
  • Intellectual Disability / etiology
  • Male
  • Mutation / genetics*
  • Optic Nerve / pathology*
  • Phenotype
  • Selenoproteins / deficiency*


  • Selenoproteins
  • Amino Acyl-tRNA Synthetases
  • O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, human

Supplementary concepts

  • Pontocerebellar Hypoplasia