Early-onset parkinsonism in PPP2R5D-related neurodevelopmental disorder

Eur J Med Genet. 2021 Jan;64(1):104123. doi: 10.1016/j.ejmg.2020.104123. Epub 2020 Dec 15.


PPP2R5D-related neurodevelopmental disorder (NDD) is a rare autosomal-dominant disease with developmental delay and mild to severe intellectual disability. So far, fewer than 30 affected individuals with mostly recurrent, de novo missense variants in PPP2R5D were reported. Recently, parkinsonism with an onset between 20 and 40 years was reported in four adult individuals with the same p.(Glu200Lys) variant in PPP2R5D. By trio exome sequencing we now identified the variant p.(Glu198Lys) in a 29 year old woman presenting with typical clinical manifestations of PPP2R5D-related neurodevelopmental disorder and additionally with motor decline and levodopa responsive, early-onset parkinsonism from her mid-twenties on. Accordingly, a clear reduction of dopamine transporter in the striatum on both sides was revealed by brain scintigraphy. Our findings further expand the molecular and clinical spectrum of PPP2R5D-related NDD and confirm the association with parkinsonism in early adulthood. This has marked implications for prognosis of PPP2R5D-related NDDs and for the therapeutic management of motor decline and parkinson-like symptoms in affected individuals.

Keywords: Neurodevelopmental disorder; PPP2R5D; Parkinson's disease; Parkinsonism.

Publication types

  • Case Reports

MeSH terms

  • Age of Onset
  • Antiparkinson Agents / therapeutic use
  • Corpus Striatum / diagnostic imaging
  • Female
  • Humans
  • Levodopa / therapeutic use
  • Mutation, Missense
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / genetics*
  • Parkinsonian Disorders / pathology
  • Phenotype
  • Protein Phosphatase 2 / genetics*
  • Young Adult


  • Antiparkinson Agents
  • PPP2R5D protein, human
  • Levodopa
  • Protein Phosphatase 2