A novel homozygous splice-site mutation in the SPTBN4 gene causes axonal neuropathy without intellectual disability

Eur J Med Genet. 2020 Apr;63(4):103826. doi: 10.1016/j.ejmg.2019.103826. Epub 2019 Dec 16.


Mutations in spectrin beta non-erythrocytic 4 (SPTBN4) have been linked to congenital hypotonia, intellectual disability and motor neuropathy. Here we report on two siblings with a homozygous splice-site mutation in the SPTBN4 gene, lacking previously reported features of the disorder such as seizures, feeding difficulties, respiratory difficulties or profound intellectual disability. Our findings indicate that muscular hypotonia, myopathic facies with ptosis and axonal neuropathy can be the core clinical features in the SPTBN4 disorder and suggest that SPTBN4 mutation analysis should be considered in infants with marked axonal neuropathy.

Keywords: Axonal neuropathy; Ptosis; SPTBN4; Spectrin beta non-erythrocytic 4.

Publication types

  • Case Reports

MeSH terms

  • Axons / pathology*
  • Axons / ultrastructure
  • Child
  • Child, Preschool
  • Female
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Hereditary Sensory and Motor Neuropathy / pathology
  • Homozygote
  • Humans
  • Male
  • Muscle Hypotonia / genetics*
  • Mutation
  • Phenotype
  • Protein Isoforms / genetics*
  • Spectrin / genetics*


  • Protein Isoforms
  • Spectrin