Infantile neuroaxonal dystrophy and PLA2G6-associated neurodegeneration: An update for the diagnosis

Brain Dev. 2017 Feb;39(2):93-100. doi: 10.1016/j.braindev.2016.08.012. Epub 2016 Nov 21.


Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder characterized by infantile onset of rapid motor and cognitive regression and hypotonia evolving into spasticity. Recessively inherited mutations of the PLA2G6 gene are causative of infantile neuroaxonal dystrophy and other PLA2G6-associated neurodegeneration, which includes conditions known as atypical neuroaxonal dystrophy, Karak syndrome and early-onset dystonia-parkinsonism with cognitive impairment. Phenotypic spectrum continues to evolve and genotype-phenotype correlations are currently limited. Due to the overlapping phenotypes and heterogeneity of clinical findings characterization of the syndrome is not always achievable. We reviewed the most recent clinical and neuroradiological information in the way to make easier differential diagnosis with other degenerative disorders in the paediatric age. Recognizing subtle signs and symptoms is a fascinating challenge to drive towards better diagnostic and genetic investigations.

Keywords: Atypical NAD; Infantile neuroaxonal dystrophy; Neurodegeneration with brain iron accumulation; PLA2G6; PLAN.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Brain / diagnostic imaging
  • Brain / physiopathology
  • Child
  • Child, Preschool
  • Early Diagnosis
  • Group VI Phospholipases A2 / genetics*
  • Humans
  • Infant
  • Neuroaxonal Dystrophies / diagnosis*
  • Neuroaxonal Dystrophies / genetics*
  • Neuroaxonal Dystrophies / physiopathology
  • Neurodegenerative Diseases / diagnosis*
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / physiopathology


  • Group VI Phospholipases A2
  • PLA2G6 protein, human