Abstract
BACKGROUND: SYNGAP1 is a significant genetic risk factor for global developmental delay, autism spectrum disorder, and epileptic encephalopathy. De novo loss-of-function variants in this gene cause a neurodevelopmental disorder, for example, early-onset and drug-refractory seizures. We report two children with global developmental delay and epileptic encephalopathy, which are caused by SYNGAP1 gene novel mutations, and drug treatment is effective. CASE PRESENTATION: We report a boy and a girl presented with global developmental delay when they were young babies; as they grew up, cognitive impairment and social-communication disorder became more and more prominent; unfortunately, the patients developed into various seizure types, including eyelid myoclonia, myoclonic and absences when the boy was 1 year 8 mouths old and the girl was 3 years old. The two patients were found two previously unknown mutations by high throughput sequencing [c.3271_ c.3272insT; (p.L1091L fs*62), c.2515A > T (p.K839*)] in exon 15 of the SYNGAP in the proband. Sanger sequencing confirmed the heterozygous nature, and neither of their parents carried the same mutation. The girl treated with valproic acid and prednisone became seizure-free, and valproic acid and levetiracetam combined with clonazepam were influential in the other. CONCLUSIONS: The global developmental delay and epileptic encephalopathy of the children were probably due to the pathogenic mutation of the SYNGAP1 gene, and prednisone and clonazepam may be effective in achieving seizure-free.