title: Infantile neuroaxonal dystrophy: what's most important for the diagnosis?
abstract: OBJECTIVE
  Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder, with onset in the first 2 years of life. Mutations in the PLA2G6 gene were identified in patients with infantile neuroaxonal dystrophy. Our purpose was to review clinical, neurophysiologic, neuroradiologic and neuropathological features of our patients in order to identify the earliest signs of disease. We also correlate these data with the genotype in the mutation positive patients.
  
  
  METHODS
  We reviewed the clinical reports, neurophysiologic and neuropathological studies and brain imaging of our patients. In five patients molecular analysis of the PLA2G6 gene was performed.
  
  
  RESULTS
  We report 10 patients with infantile neuroaxonal dystrophy. Earliest symptoms presented between 6 and 18 months of age. The first manifestations were arrest in the acquisition of milestones or regression. The first neurological signs were generalized hypotonia and pyramidal signs. Fast rhythms on EEG were observed in all patients. Brain imaging studies showed cerebellar atrophy in all patients, with signal hyperintensity in the cerebellar cortex on T2-weighted images in five. All cases had characteristic axonal spheroids on skin biopsy. Mutations in the PLA2G6 gene were identified in the five patients studied. Three of them had the same homozygous mutations 2370T> G, Y790X.
  
  
  CONCLUSIONS
  Though mutations were detected in the patients studied, a clear genotype-phenotype correlation could not be ascertained. In the appropriate clinical context, characteristic brain imaging and fast rhythms on EEG can support the decision to perform molecular analysis and avoid skin biopsy to confirm diagnosis.
authors: Department of Child Neurology, Hospital de Crianças Maria Pia, Rua da Boavista, 827, 4050-111 Porto, Portugal. ines.carrilho@tvtel.pt
authors: Inês
authors: I
authors: Carrilho
authors: Manuela
authors: M
authors: Santos
authors: António
authors: A
authors: Guimarães
authors: João
authors: J
authors: Teixeira
authors: Rui
authors: R
authors: Chorão
authors: Márcia
authors: M
authors: Martins
authors: Cristina
authors: C
authors: Dias
authors: Allison
authors: A
authors: Gregory
authors: Shawn
authors: S
authors: Westaway
authors: Thuy
authors: T
authors: Nguyen
authors: Susan
authors: S
authors: Hayflick
authors: Clara
authors: C
authors: Barbot
mesh_terms: D000293:Adolescent; D000328:Adult; D001284:Atrophy; D001921:Brain / Q000473:pathology; D002525:Cerebellar Cortex / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D054522:Group VI Phospholipases A2 / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D019150:Neuroaxonal Dystrophies / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D004247:DNA; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human