{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:47:49Z","timestamp":1778932069519,"version":"3.51.4"},"reference-count":17,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T00:00:00Z","timestamp":1569542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Center for Advancing Translational Sciences of the National Institutes of Health","award":["KL2TR001879"],"award-info":[{"award-number":["KL2TR001879"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>Aicardi Gouti\u00e8res 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 Gouti\u00e8res 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 Gouti\u00e8res syndrome. To characterize the clinical presentation in Aicardi Gouti\u00e8res syndrome, early features were collected from an international cohort of children (n = 100) with genetically confirmed Aicardi Gouti\u00e8res 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 Gouti\u00e8res 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 Gouti\u00e8res 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.<\/jats:p>","DOI":"10.1177\/0883073819870944","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T05:44:58Z","timestamp":1569563098000},"page":"7-16","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":65,"title":["Developmental Outcomes of Aicardi Gouti\u00e8res Syndrome"],"prefix":"10.1177","volume":"35","author":[{"given":"Laura","family":"Adang","sequence":"first","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, 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