PLA2G6-associated neurodegeneration (PLAN): further expansion of the clinical, radiological and mutation spectrum associated with infantile and atypical childhood-onset disease

Mol Genet Metab. 2014 Jun;112(2):183-9. doi: 10.1016/j.ymgme.2014.03.008. Epub 2014 Mar 29.


Phospholipase A2 associated neurodegeneration (PLAN) is a major phenotype of autosomal recessive Neurodegeneration with Brain Iron Accumulation (NBIA). We describe the clinical phenotypes, neuroimaging features and PLA2G6 mutations in 5 children, of whom 4 presented with infantile neuroaxonal dystrophy (INAD). One other patient was diagnosed with the onset of PLAN in childhood, and our report highlights the diagnostic challenges associated with this atypical PLAN subtype. In this series, the neuroradiological relevance of classical PLAN features as well as apparent claval hypertrophy' is explored. Novel PLA2G6 mutations were identified in all patients. PLAN should be considered not only in patients presenting with a classic INAD phenotype but also in older patients presenting later in childhood with non-specific progressive neurological features including social communication difficulties, gait disturbance, dyspraxia, neuropsychiatric symptoms and extrapyramidal motor features.

Keywords: INAD; NBIA; Neurodegeneration with brain iron accumulation; PLA2G6; PLAN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Brain / diagnostic imaging
  • Brain / pathology
  • Child, Preschool
  • Female
  • Genetic Variation
  • Group VI Phospholipases A2 / genetics*
  • Humans
  • Infant
  • Ireland
  • Male
  • Mutation
  • Neuroaxonal Dystrophies / diagnostic imaging*
  • Neuroaxonal Dystrophies / genetics
  • Neuroaxonal Dystrophies / pathology*
  • Phenotype
  • Radiography
  • United Kingdom


  • Group VI Phospholipases A2
  • PLA2G6 protein, human