TY - JOUR
T1 - Infantile neuroaxonal dystrophy
T2 - What's most important for the diagnosis?
AU - Carrilho, Inês
AU - Santos, Manuela
AU - Guimarães, António
AU - Teixeira, João
AU - Chorão, Rui
AU - Martins, Márcia
AU - Dias, Cristina
AU - Gregory, Allison
AU - Westaway, Shawn
AU - Nguyen, Thuy
AU - Hayflick, Susan
AU - Barbot, Clara
N1 - Funding Information:
PLA2G6 mutation analysis was performed at the Hayflick Laboratory, Oregon Health & Science University, Portland, OR97239, USA. This work was supported by grants from the National Institute of Child Health and Human Development, the National Eye Institute, L’Association Internationale De Dystrophie Neuro Axonale Infantile, and the NBIA Disorders Association. This study was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), Grant no. UL1 RR024140 01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.
PY - 2008/11
Y1 - 2008/11
N2 - Background and aims: 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.
AB - Background and aims: 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.
KW - Cerebellar atrophy
KW - EEG fast rhythms
KW - Infantile neuroaxonal dystrophy
KW - PLA2G6 gene
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U2 - 10.1016/j.ejpn.2008.01.005
DO - 10.1016/j.ejpn.2008.01.005
M3 - Article
C2 - 18359254
AN - SCOPUS:53049095219
SN - 1090-3798
VL - 12
SP - 491
EP - 500
JO - European Journal of Paediatric Neurology
JF - European Journal of Paediatric Neurology
IS - 6
ER -