title: Validation of the finding of hypertrophy of the clava in infantile neuroaxonal dystrophy/PLA2G6 by biometric analysis.
abstract: BACKGROUND
  Infantile neuroaxonal dystrophy (INAD), an autosomal recessive neurodegenerative disorder due to PLA2G6 mutation, is classified both as a PLA2G6-associated neurodegeneration (PLAN) disorder and as one of the neurodegeneration with brain iron accumulation (NBIA) disorders. Age of onset and clinical presentation in INAD is variable. Typically described imaging features of cerebellar atrophy, cerebellar cortex bright FLAIR signal, and globus pallidus iron deposition are variable or late findings. We characterize clinical and neuroimaging phenotypes in nine children with confirmed PLA2G6 mutations and show a useful imaging feature, clava hypertrophy, which may aid in earlier identification of patients. Measurements of the clava confirm actual enlargement, rather than apparent enlargement due to volume loss of the other brain stem structures.
  
  
  METHODS
  A retrospective clinical and MRI review was performed. Brain stem measurements were performed and compared with age-matched controls.
  
  
  RESULTS
  We identified nine patients, all with novel PLA2G6 gene mutations. MRI, available in eight, showed clava hypertrophy, regardless of age or the absence of other more typically described neuroimaging findings. Brain autopsy in our cohort confirmed prominent spheroid bodies in the clava nuclei.
  
  
  CONCLUSIONS
  Clava hypertrophy is an important early imaging feature which may aid in indentification of children who would benefit from specific testing for PLA2G6 mutations.
authors: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.|Department of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman.
authors: A
authors: A
authors: Al-Maawali
authors: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.|Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: G
authors: G
authors: Yoon
authors: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.|Division of Genetics, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
authors: A S
authors: AS
authors: Feigenbaum
authors: Division of Pathology, DPLM, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: W C
authors: WC
authors: Halliday
authors: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: J T R
authors: JT
authors: Clarke
authors: Division of Paediatric Neuroradiology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Ontario, Canada.
authors: H M
authors: HM
authors: Branson
authors: Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors: B L
authors: BL
authors: Banwell
authors: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.|The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: D
authors: D
authors: Chitayat
authors: Division of Paediatric Neuroradiology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Ontario, Canada. susan.blaser@sickkids.ca.
authors: Susan I
authors: SI
authors: Blaser
mesh_terms: D001699:Biometry / Q000379:methods*; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006801:Humans; D006984:Hypertrophy; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D019150:Neuroaxonal Dystrophies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
keywords: Atypical INAD (NBIA2B); Clava; INAD (NBIA2A); PLAN/PLA2G6; Seitelberger’s disease