Late-Onset Aicardi-Goutières Syndrome: A Characterization of Presenting Clinical Features.
Adolescent
Age of Onset
Autoimmune Diseases of the Nervous System
/ complications
Chilblains
/ etiology
Child
Child, Preschool
Chronic Pain
/ etiology
Developmental Disabilities
/ etiology
Disease Progression
Female
Fever
/ etiology
Humans
Hypothermia
/ etiology
Infant
Inflammation
/ etiology
Male
Motor Skills
/ physiology
Nervous System Malformations
/ complications
Retrospective Studies
ADAR1
Aicardi-Goutières syndrome
IFIH1
Leukodystrophy
RNASEH2B
SAMHD1
Type I interferonopathy
Journal
Pediatric neurology
ISSN: 1873-5150
Titre abrégé: Pediatr Neurol
Pays: United States
ID NLM: 8508183
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
08
09
2020
revised:
23
10
2020
accepted:
27
10
2020
pubmed:
12
12
2020
medline:
15
12
2021
entrez:
11
12
2020
Statut:
ppublish
Résumé
Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy characterized by early onset of severe neurological injury with intracranial calcifications, leukoencephalopathy, and systemic inflammation. Increasingly, a spectrum of neurological dysfunction and presentation beyond the infantile period is being recognized in AGS. The aim of this study was to characterize late-infantile and juvenile-onset AGS. We conducted a multi-institution review of individuals with AGS who were older than one year at the time of presentation, including medical history, imaging characteristics, and suspected diagnoses at presentation. Thirty-four individuals were identified, all with pathogenic variants in RNASEH2B, SAMHD1, ADAR1, or IFIH1. Most individuals had a history of developmental delay and/or systemic symptoms, such as sterile pyrexias and chilblains, followed by a prodromal period associated with increasing symptoms. This was followed by an abrupt onset of neurological decline (fulminant phase), with a median onset at 1.33 years (range 1.00 to 17.68 years). Most individuals presented with a change in gross motor skills (97.0%), typically with increased tone (78.8%). Leukodystrophy was the most common magnetic resonance imaging finding (40.0%). Calcifications were less common (12.9%). This is the first study to characterize the presentation of late-infantile and juvenile onset AGS and its phenotypic spectrum. Late-onset AGS can present insidiously and lacks classical clinical and neuroimaging findings. Signs of early systemic dysfunction before fulminant disease onset and loss of motor symptoms were common. We strongly recommend genetic testing when there is concern for sustained inflammation of unknown origins or changes in motor skills in children older than one year.
Sections du résumé
BACKGROUND
Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy characterized by early onset of severe neurological injury with intracranial calcifications, leukoencephalopathy, and systemic inflammation. Increasingly, a spectrum of neurological dysfunction and presentation beyond the infantile period is being recognized in AGS. The aim of this study was to characterize late-infantile and juvenile-onset AGS.
METHODS
We conducted a multi-institution review of individuals with AGS who were older than one year at the time of presentation, including medical history, imaging characteristics, and suspected diagnoses at presentation.
RESULTS
Thirty-four individuals were identified, all with pathogenic variants in RNASEH2B, SAMHD1, ADAR1, or IFIH1. Most individuals had a history of developmental delay and/or systemic symptoms, such as sterile pyrexias and chilblains, followed by a prodromal period associated with increasing symptoms. This was followed by an abrupt onset of neurological decline (fulminant phase), with a median onset at 1.33 years (range 1.00 to 17.68 years). Most individuals presented with a change in gross motor skills (97.0%), typically with increased tone (78.8%). Leukodystrophy was the most common magnetic resonance imaging finding (40.0%). Calcifications were less common (12.9%).
CONCLUSIONS
This is the first study to characterize the presentation of late-infantile and juvenile onset AGS and its phenotypic spectrum. Late-onset AGS can present insidiously and lacks classical clinical and neuroimaging findings. Signs of early systemic dysfunction before fulminant disease onset and loss of motor symptoms were common. We strongly recommend genetic testing when there is concern for sustained inflammation of unknown origins or changes in motor skills in children older than one year.
Identifiants
pubmed: 33307271
pii: S0887-8994(20)30346-5
doi: 10.1016/j.pediatrneurol.2020.10.012
pmc: PMC7856674
mid: NIHMS1653514
pii:
doi:
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-6Subventions
Organisme : NINDS NIH HHS
ID : K23 NS114113
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS106845
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS115052
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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