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Pediatr Neurol. 2018 Oct;87:48-56. doi: 10.1016/j.pediatrneurol.2018.04.012. Epub 2018 May 7.

Infantile Spasms of Unknown Cause: Predictors of Outcome and Genotype-Phenotype Correlation.

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Department of Neurology and Division of Epilepsy, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Medical Genetics and Department of Pediatrics, Stanford University, Stanford, California.
Department of Neurology, Royal Children's Hospital, Parkville, Victoria, Australia.
Department of Epidemiology and Biostatistics/UCSF, University of California San Francisco, San Francisco, California.
The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Epilepsy Research Centre, Austin Health, University of Melbourne, Melbourne, Victoria, Australia.
Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, California. Electronic address:



No large-scale studies have specifically evaluated the outcomes of infantile spasms (IS) of unknown cause, previously known as cryptogenic or idiopathic. The Epilepsy Phenome/Genome Project aimed to characterize IS of unknown cause by phenotype and genotype analysis.


We undertook a retrospective multicenter observational cohort of 133 individuals within the Epilepsy Phenome/Genome Project database met criteria for IS of unknown cause with at least six months of follow-up data. Clinical medical records, imaging, and electroencephalography were examined.


Normal development occurred in only 15% of IS of unknown cause. The majority (85%) had clinically documented developmental delay (15% mild, 20% moderate, and 50% severe) at last assessment (median 2.7 years; interquartile interval 1.71-6.25 years). Predictors of positive developmental outcomes included no delay prior to IS (P < 0.001), older age of IS onset (median six months old), and resolution of IS after initial treatment (P < 0.001). Additional seizures after IS occurred in 67%, with predictors being seizures prior to IS (P = 0.018), earlier age of IS onset (median five months old), and refractory IS (P = 0.008). On a research basis, whole exome sequencing identified 15% with de novo variants in known epilepsy genes. Individuals with a genetic finding were more likely to have poor developmental outcomes (P = 0.035).


The current study highlights the predominately unfavorable developmental outcomes and that subsequent seizures are common in children with IS of unknown cause. Ongoing genetic evaluation of IS of seemingly unknown cause is likely to yield a diagnosis and provide valuable prognostic information.


Cryptogenic infantile spasms; Developmental outcomes; Epilepsy; Epilepsy genetics; Epileptic encephalopathy; Genotype-phenotype; Infantile spasms; Seizures

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