Objective To report the clinical manifestations and genetic characteristics of a child with epilepsy caused by a de novo mutation in the HCN1 gene. Methods The clinical data and HCN1 gene mutation characteristics of a child with epilepsy admitted to our hospital in May 2020 were analyzed, and the relevant domestic and foreign literature were reviewed. Results A 7-month-old male child developed epileptic seizures for the first time, with various forms of seizures, beginning with atonic seizures, followed by febrile seizures, focal seizures, generalized tonic-clonic seizures, and absence seizures. During hospitalization, his cerebrospinal fluid (CSF), hematuria tandem mass spectrometry (HVMS), cranial imaging and other examinations showed no obvious abnormality. The results of genetic testing showed that there was a heterozygous missense mutation c.839A>C (p.Gln280Pro) in the second exon region of the HCN1 gene of the child, and neither of his parents carried the mutation, suggesting that the mutation is novel. According to the guidelines of America Society of Medical Genetics and Genomics (ACMG), the variation was rated as likely pathogenic. The child was diagnosed with HCN1 gene mutation-related epilepsy and was treated with a combination of levetiracetam and sodium valproate. The child’s epilepsy was well controlled and discharged when his condition was stable. Following up to now after discharge, the patient is prone to convulsions during the course of febrile disease, but his growth and development level is normal. Literature review shows that HCN1 gene mutation-related epilepsy is mainly de novo in patients, most of which are located in the 2nd and 4th exon regions. Conclusions For children with clinically unexplained early-onset epilepsy, gene sequencing should be performed as soon as possible to analyze possible genetic etiology, which will help confirm the diagnosis and guide treatment.

Citation： SHI Jingyu, LI Jianwei. A case report of epilepsy caused by a de novo mutation of HCN1 gene and literature review. Journal of Epilepsy, 2022, 8(1): 52-56. doi: 10.7507/2096-0247.20220013 Copy