[The etiology of 340 infants with early-onset epilepsy]

Objective: To investigate the etiology of epilepsy onset before 6 months old and improve clinical understanding. Methods: The medical history, electroencephalogram, brain imaging, genetic examination and other clinical data of 340 patients who were diagnosed with epilepsy with onset under 6 months of age and were hospitalized in the Department of Neurology, Beijing Children's Hospital, Capital Medical University between January 2017 and December 2018 were retrospectively analyzed. Rank sum test was used to compare the ages of onset of different etiologic groups. Results: Of the 340 patients, 196 were males and 144 were females. The age of onset was 90.5 (48.0, 135.5) days. In the 250 (73.5%) underwent genetic test, 103 (41.2%) had pathogenic or likely pathogenic variants, involving 43 single gene variants and 2 chromosomal abnormalities. Seventy-nine patients (23.2%) had genetic etiology, 66 (19.4%) had structural etiology, 19 (5.6%) had metabolic etiology, 13 (3.8%) had multiple etiologies, and 163 (47.9%) had unknown etiology. In the 79 cases with genetic etiology, 30 single gene variants were detected, including 19 cases of PRRT2, 10 cases of KCNQ2, 7 cases of SCN1A, 6 cases of SCN2A, 6 cases of STXBP1, 5 cases of CDKL5, 2 cases of ARX, and 1 case of each of 23 gene variants. Two cases had chromosomal abnormalities which were 21-trisomy and 16p11.2 microdeletion syndrome respectively. Among the 66 cases with structural etiologies, 37 cases had acquired factors such as perinatal brain injury, 28 cases had congenital factors such as cortical malformation and 1 case was perinatal brain injury combined megalencephaly. The onset age of genetic etiology was 95 (26, 128) days, that of structural etiology was 90 (58, 30) days, and that of metabolic etiology was 57 (30, 90) days. The onset age of metabolic etiology was earlier than that of structural etiology (U=436.500, P=0.044). Conclusions: Genetic etiology is the most common defined etiology of infants with early-onset epilepsy aged 0-6 months, and there are certain differences in the age of onset between different etiologies. Proper application of genetic test is helpful to identify the etiology and guide treatment.