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Objective: Infantile spasms (IS) is a common epilepsy syndrome in infancy. Genetically based birth defects are among the many causes of infantile spasms. Genetic diagnosis can reveal the etiology of IS and guide treatment strategies and genetic counseling, but significant challenges surround the choice of appropriate genetic diagnostic strategies to improve the diagnostic yield in IS.Methods: For a cohort of Chinese patients with IS, appropriate genetic testing methods were selected according to etiological classification. Methods included karyotyping, copy number variation detection, single-gene sequencing, targeted sequencing panel, and whole-exome sequencing.Results: A total of 728 children with IS from fifteen provinces and municipalities in China from June 2015 to October 2020 were recruited in the study. Among them, 436 were males (59.9%). The median age was 9.46 months. The diagnostic yield of our study was 31.5% (185/587). The top five causative genes were TSC2 (n = 91), STXBP1 (n = 21), TSC1 (n = 15), SCN2A (n = 6), and CDKL5 (n = 6). The genetic diagnostic yield was 100% in Down syndrome (n = 1), neurofibromatosis (n = 2), and methylmalonic acidemia (n = 2), 83.5% in tuberous sclerosis complex (n = 127), and 16.7% in unsolved infantile spasms (n = 442). Different genetic testing methods for different etiologies show large differences in diagnostic yields.Conclusion: This study demonstrates that appropriate genetic testing procedures for different phenotypes can ensure a high diagnostic yield. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyze the therapeutic effect of sirolimus on seizures in pediatric patients with tuberous sclerosis.Methods: We first compared the efficacy of controlling seizures in all patients after they had taken sirolimus for one year, and then we performed a subgroup analysis based on whether the administered antiepileptic drugs were changed to determine whether the efficacy was associated with changes of antiepileptic drugs.Results: A total of 91 eligible children were enrolled. The response rate was 78.0 % (71/91), and 47.2 % (43/91) of all patients were became seizure-free. The improvement in seizure control before and after treatment with sirolimus was significant (p < 0.001). In the AEDs unaltered group, 34 were responders (34/45, 75.6 %, 95 % CI 17.4-88.3), of which 24 were seizure-free (24/34, 70.6 %). In the AEDs-altered group, 37 were responders (37/46, 80.4 %, 95 % CI 56.7-88.1), of which 19 were seizure-free (19/37, 51.4 %). There was no significant difference between the two groups for reductions in rate of seizure frequency (p = 0.308). In the patients with refractory epilepsy, treatment with sirolimus was also effective (p = 0.01). Logistic regression analysis showed that age was an important factor affecting outcome of epilepsy (p = 0.003, 95 % CI 2.05-38.31). No Grade 3 or 4 adverse events were noted during the follow-up.Conclusions: Sirolimus has a significant effect on seizures associated with tuberous sclerosis complex (TSC), with no or only moderate adverse events after long-term administration. Sirolimus could be used as the first-line medication for pediatric patients with TSC-associated epilepsy. [ABSTRACT FROM AUTHOR]