Recurrent RTTN mutation leading to severe microcephaly, polymicrogyria and growth restriction

Eur J Med Genet. 2018 Dec;61(12):755-758. doi: 10.1016/j.ejmg.2018.08.001. Epub 2018 Aug 16.


Autosomal recessive missense Rotatin (RTTN) mutations are responsible for syndromic forms of malformation of cortical development, ranging from isolated polymicrogyria to microcephaly associated with primordial dwarfism and other major malformations. We identified, by trio based whole exome sequencing, a homozygous missense mutation in the RTTN gene (c.2953A > G; p.(Arg985Gly)) in one Moroccan patient from a consanguineous family. The patient showed early onset primary microcephaly, detected in the fetal period, postnatal growth restriction, encephalopathy with hyperkinetic movement disorders and self-injurious behavior with sleep disturbance. Brain MRI showed an extensive dysgyria associated with nodular heterotopia, large interhemispheric arachnoid cyst and corpus callosum hypoplasia.

Keywords: Hyperkinetic movement disorders; Microlissencephaly; Primary microcephaly; Primordial dwarfism; RTTN.

MeSH terms

  • Brain / diagnostic imaging
  • Brain / pathology
  • Carrier Proteins / genetics*
  • Cell Cycle Proteins
  • Child
  • Child, Preschool
  • Consanguinity
  • Databases, Genetic
  • Dwarfism / diagnostic imaging
  • Dwarfism / genetics*
  • Dwarfism / pathology
  • Female
  • Homozygote
  • Humans
  • Male
  • Microcephaly / diagnostic imaging
  • Microcephaly / genetics*
  • Microcephaly / pathology
  • Morocco / epidemiology
  • Mutation, Missense
  • Pedigree
  • Phenotype
  • Polymicrogyria / diagnostic imaging
  • Polymicrogyria / genetics*
  • Polymicrogyria / pathology


  • Carrier Proteins
  • Cell Cycle Proteins
  • RTTN protein, human