Developmental Outcomes of Aicardi Goutières Syndrome.
J Child Neurol
; 35(1): 7-16, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31559893
ABSTRACT
Aicardi Goutières syndrome is a monogenic interferonopathy caused by abnormalities in the intracellular nucleic acid sensing machinery (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1). Most individuals affected by Aicardi Goutières syndrome exhibit some degree of neurologic impairment, from spastic paraparesis with relatively preserved cognition to tetraparesis and severe intellectual disability. Because of this heterogeneity, it is important to fully characterize the developmental trajectory in Aicardi Goutières syndrome. To characterize the clinical presentation in Aicardi Goutières syndrome, early features were collected from an international cohort of children (n = 100) with genetically confirmed Aicardi Goutières syndrome. There was a heterogeneous age of onset, with overlapping clusters of presenting symptoms altered mental status, systemic inflammatory symptoms, and acute neurologic disability. Next, we created genotype-specific developmental milestone acquisition curves. Individuals with microcephaly or TREX1-related Aicardi Goutières syndrome secondary were the most severely affected and less likely to reach milestones, including head control, sitting, and nonspecific mama/dada. Individuals affected by SAMHD1, IFIH1, and ADAR attained the most advanced milestones, with 44% achieving verbal communication and 31% independently ambulating. Retrospective function scales (Gross Motor Function Classification System, Manual Ability Classification System, and Communication Function Classification System) demonstrated that two-thirds of the Aicardi Goutières syndrome population are severely affected. Our results suggest multifactorial influences on developmental trajectory, including a strong contribution from genotype. Further studies are needed to identify the additional factors that influence overall outcomes to better counsel families and to design clinical trials with appropriate clinical endpoints.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenvolvimento Infantil
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Doenças Autoimunes do Sistema Nervoso
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Destreza Motora
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Malformações do Sistema Nervoso
Tipo de estudo:
Guideline
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Observational_studies
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Prognostic_studies
Limite:
Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
J Child Neurol
Ano de publicação:
2020
Tipo de documento:
Article