Infantile neuroaxonal dystrophy

What's most important for the diagnosis?

Inês Carrilho, Manuela Santos, António Guimarães, João Teixeira, Rui Chorão, Márcia Martins, Cristina Dias, Allison Gregory, Shawn Westaway, Thuy Nguyen, Susan Hayflick, Clara Barbot

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)491-500
Number of pages10
JournalEuropean Journal of Paediatric Neurology
Volume12
Issue number6
DOIs
StatePublished - Nov 2008

Fingerprint

Neuroaxonal Dystrophies
Mutation
Neuroimaging
Electroencephalography
Genes
Biopsy
Skin
Cerebellar Cortex
Muscle Hypotonia
Genetic Association Studies
Neurodegenerative Diseases
Atrophy

Keywords

  • Cerebellar atrophy
  • EEG fast rhythms
  • Infantile neuroaxonal dystrophy
  • PLA2G6 gene

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health

Cite this

Carrilho, I., Santos, M., Guimarães, A., Teixeira, J., Chorão, R., Martins, M., ... Barbot, C. (2008). Infantile neuroaxonal dystrophy: What's most important for the diagnosis? European Journal of Paediatric Neurology, 12(6), 491-500. https://doi.org/10.1016/j.ejpn.2008.01.005

Infantile neuroaxonal dystrophy : What's most important for the diagnosis? / Carrilho, Inês; Santos, Manuela; Guimarães, António; Teixeira, João; Chorão, Rui; Martins, Márcia; Dias, Cristina; Gregory, Allison; Westaway, Shawn; Nguyen, Thuy; Hayflick, Susan; Barbot, Clara.

In: European Journal of Paediatric Neurology, Vol. 12, No. 6, 11.2008, p. 491-500.

Research output: Contribution to journalArticle

Carrilho, I, Santos, M, Guimarães, A, Teixeira, J, Chorão, R, Martins, M, Dias, C, Gregory, A, Westaway, S, Nguyen, T, Hayflick, S & Barbot, C 2008, 'Infantile neuroaxonal dystrophy: What's most important for the diagnosis?', European Journal of Paediatric Neurology, vol. 12, no. 6, pp. 491-500. https://doi.org/10.1016/j.ejpn.2008.01.005
Carrilho, Inês ; Santos, Manuela ; Guimarães, António ; Teixeira, João ; Chorão, Rui ; Martins, Márcia ; Dias, Cristina ; Gregory, Allison ; Westaway, Shawn ; Nguyen, Thuy ; Hayflick, Susan ; Barbot, Clara. / Infantile neuroaxonal dystrophy : What's most important for the diagnosis?. In: European Journal of Paediatric Neurology. 2008 ; Vol. 12, No. 6. pp. 491-500.
@article{092cd9da75ec4d9bbd8446056d68da67,
title = "Infantile neuroaxonal dystrophy: What's most important for the diagnosis?",
abstract = "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.",
keywords = "Cerebellar atrophy, EEG fast rhythms, Infantile neuroaxonal dystrophy, PLA2G6 gene",
author = "In{\^e}s Carrilho and Manuela Santos and Ant{\'o}nio Guimar{\~a}es and Jo{\~a}o Teixeira and Rui Chor{\~a}o and M{\'a}rcia Martins and Cristina Dias and Allison Gregory and Shawn Westaway and Thuy Nguyen and Susan Hayflick and Clara Barbot",
year = "2008",
month = "11",
doi = "10.1016/j.ejpn.2008.01.005",
language = "English (US)",
volume = "12",
pages = "491--500",
journal = "European Journal of Paediatric Neurology",
issn = "1090-3798",
publisher = "W.B. Saunders Ltd",
number = "6",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=53049095219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53049095219&partnerID=8YFLogxK

U2 - 10.1016/j.ejpn.2008.01.005

DO - 10.1016/j.ejpn.2008.01.005

M3 - Article

VL - 12

SP - 491

EP - 500

JO - European Journal of Paediatric Neurology

JF - European Journal of Paediatric Neurology

SN - 1090-3798

IS - 6

ER -