Objective:

To retrospectively analyzed the de novo mutations in a Chinese Infantile spasms cohort of unknown etiology, and describe the efficacy of Levetiracetam in infantile spasms patients with a de novo STXBP1 mutation.

Methods：

Targeted next-generation sequencing (NGS) of 153 epilepsy-related candidate genes was applied for 289 infantile spasms patients with unknown cause. The therapeutic effects of Levetiracetam, observed in four patients with de novo mutation in STXBP1 gene.

Results：

Twenty-five de novo mutations were detected. One of these patients carried two de novo mutations, STXBP1 and DIAPH3. The recurrent de novo mutation included CDKL5 (n = 5), STXBP1 (n = 4), ARX (n = 2), KCNB1 (n = 2), SCN2A (n = 2). The mutation of SCN8A, TCF4, DIAPH3 and KCNMA1 were reported for the first time in ISs phenotype.

The mean duration of follow-up in 4 patients with de novo mutation in STXBP1 gene was 12.74 months (7.3-19.77 months). After treatment with Levetiracetam, 3 patients were seizure free after LEV was added to 50mg / kg.d. The mean durations from seizure free to normalized EEG were 2.83 months (0.25-25 months). The frequency of seizure in patient with 2 gene de novo mutations was decreased.

Significance：De-novo mutations were important causes in infantile spasms patients. Clinical targeted panel sequencing was a cost-effective way to identify de novo mutation in infantile spasms. According to the diagnosis with de novo STXBP1 mutation, the precision treatment with Levetiracetam can significantly improve the prognosis of STXBP1-related infantile spasms.