Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published cases

Abstract Purpose Aicardi syndrome is a rare epileptic encephalopathy, almost exclusively affecting girls. It was first described as a triad of infantile spasms, chorioretinal defects and agenesis of the corpus callosum. The etiology remains unknown and there is uncertainty on best practice therapy a...

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Main Authors: Oliver Y. Urban, Jan H. Driedger, Sven F. Garbade, Georg F. Hoffmann, Stefan Kölker, Markus Ries, Steffen Syrbe
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Orphanet Journal of Rare Diseases
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Online Access:https://doi.org/10.1186/s13023-024-03375-8
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author Oliver Y. Urban
Jan H. Driedger
Sven F. Garbade
Georg F. Hoffmann
Stefan Kölker
Markus Ries
Steffen Syrbe
author_facet Oliver Y. Urban
Jan H. Driedger
Sven F. Garbade
Georg F. Hoffmann
Stefan Kölker
Markus Ries
Steffen Syrbe
author_sort Oliver Y. Urban
collection DOAJ
description Abstract Purpose Aicardi syndrome is a rare epileptic encephalopathy, almost exclusively affecting girls. It was first described as a triad of infantile spasms, chorioretinal defects and agenesis of the corpus callosum. The etiology remains unknown and there is uncertainty on best practice therapy and outcome. We aimed at defining quantitative clinical endpoints that will inform future research and clinical trials. Methods Quantitative natural history modeling of cases with Aicardi syndrome from published clinical reports. Main outcome measures were age at disease onset, survival and diagnostic delay. Phenotypic features of affected individuals as well as neuroradiological and ophthalmological features were descriptively stated. STROBE criteria were respected. Results Two hundred forty-five cases were available for analysis. Median age at disease onset was 2.2 months. Median diagnostic delay was 1 month. Mortality was estimated with 6% at 1 and 17% at 5 years of age. 60% of children showed the classic clinical features, while 40% met the revised diagnostic criteria. We delineate possible predictors of disease severity and of seizure control. Conclusion We provide natural history data including geographical localization of 245 published patients with Aicardi syndrome. Quantitative history modeling in rare epileptic encephalopathies will help to raise disease awareness and facilitate future clinical trials as one core element of quantitative systems pharmacology.
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spelling doaj-art-0c82f63f015e42568ee0d2d3dd12a7df2025-08-20T02:20:40ZengBMCOrphanet Journal of Rare Diseases1750-11722024-12-0119111110.1186/s13023-024-03375-8Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published casesOliver Y. Urban0Jan H. Driedger1Sven F. Garbade2Georg F. Hoffmann3Stefan Kölker4Markus Ries5Steffen Syrbe6Division of Pediatric Epileptology, Center for Pediatric and Adolescent Medicine, Clinic 1, Medical Faculty of Heidelberg, Heidelberg UniversityDivision of Pediatric Epileptology, Center for Pediatric and Adolescent Medicine, Clinic 1, Medical Faculty of Heidelberg, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Clinic 1, Medical Faculty of Heidelberg, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Clinic 1, Medical Faculty of Heidelberg, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Clinic 1, Medical Faculty of Heidelberg, Heidelberg UniversityDivision of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Clinic 1, Medical Faculty of Heidelberg, Heidelberg UniversityDivision of Pediatric Epileptology, Center for Pediatric and Adolescent Medicine, Clinic 1, Medical Faculty of Heidelberg, Heidelberg UniversityAbstract Purpose Aicardi syndrome is a rare epileptic encephalopathy, almost exclusively affecting girls. It was first described as a triad of infantile spasms, chorioretinal defects and agenesis of the corpus callosum. The etiology remains unknown and there is uncertainty on best practice therapy and outcome. We aimed at defining quantitative clinical endpoints that will inform future research and clinical trials. Methods Quantitative natural history modeling of cases with Aicardi syndrome from published clinical reports. Main outcome measures were age at disease onset, survival and diagnostic delay. Phenotypic features of affected individuals as well as neuroradiological and ophthalmological features were descriptively stated. STROBE criteria were respected. Results Two hundred forty-five cases were available for analysis. Median age at disease onset was 2.2 months. Median diagnostic delay was 1 month. Mortality was estimated with 6% at 1 and 17% at 5 years of age. 60% of children showed the classic clinical features, while 40% met the revised diagnostic criteria. We delineate possible predictors of disease severity and of seizure control. Conclusion We provide natural history data including geographical localization of 245 published patients with Aicardi syndrome. Quantitative history modeling in rare epileptic encephalopathies will help to raise disease awareness and facilitate future clinical trials as one core element of quantitative systems pharmacology.https://doi.org/10.1186/s13023-024-03375-8Aicardi syndromeNatural historyEpileptic encephalopathyInfantile spasmsAgenesis of corpus callosumChorioretinal lacunae
spellingShingle Oliver Y. Urban
Jan H. Driedger
Sven F. Garbade
Georg F. Hoffmann
Stefan Kölker
Markus Ries
Steffen Syrbe
Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published cases
Orphanet Journal of Rare Diseases
Aicardi syndrome
Natural history
Epileptic encephalopathy
Infantile spasms
Agenesis of corpus callosum
Chorioretinal lacunae
title Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published cases
title_full Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published cases
title_fullStr Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published cases
title_full_unstemmed Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published cases
title_short Systematic quantitative modeling of the natural history of Aicardi syndrome: A cross sectional study of 245 published cases
title_sort systematic quantitative modeling of the natural history of aicardi syndrome a cross sectional study of 245 published cases
topic Aicardi syndrome
Natural history
Epileptic encephalopathy
Infantile spasms
Agenesis of corpus callosum
Chorioretinal lacunae
url https://doi.org/10.1186/s13023-024-03375-8
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