Novel copy number variations and phenotypes of infantile epileptic spasms syndrome

• Published in: Clinical genetics Vol. 106; no. 2; pp. 161 - 179
• Main Authors: Cheng, Miaomiao, Bai, Ling, Yang, Ying, Liu, Wenwei, Niu, Xueyang, Chen, Yi, Tan, Quanzhen, Yang, Xiaoling, Wu, Qixi, Zhao, Han‐Qing, Zhang, Yuehua
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2024
• Subjects: Convulsions & seizures; Copy number; copy number variation; craniofacial anomaly; Epilepsy; genomic copy number variation sequencing; Hemangioma; infantile epileptic spasms syndrome; Microcephaly; Mosaicism; Phenotypes; Phenotypic variations; Seizures; treatment; treatment; copy number variation; craniofacial anomaly; infantile epileptic spasms syndrome; genomic copy number variation sequencing
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.14520

We summarize the copy number variations (CNVs) and phenotype spectrum of infantile epileptic spasms syndrome (IESS) in a Chinese cohort. The CNVs were identified by genomic copy number variation sequencing. The CNVs and clinical data were analyzed. 74 IESS children with CNVs were enrolled. 35 kinds of CNVs were identified. There were 11 deletions and 5 duplications not reported previously in IESS, including 2 CNVs not reported in epilepsy. 87.8% were de novo, 9.5% were inherited from mother and 2.7% from father. Mosaicism occurred in one patient with Xq21.31q25 duplication. 16.2% (12/74) were 1p36 deletion, and 20.3% (15/74) were 15q11‐q13 duplication. The age of seizure onset ranged from 17 days to 24 months. Seizure types included epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. All patients displayed developmental delay. Additional features included craniofacial anomaly, microcephaly, congenital heart defects, and hemangioma. 29.7% of patients were seizure‐free for more than 12 months, and 70.3% still had seizures after trying 2 or more anti‐seizure medications. In conclusion, CNVs is a prominent etiology of IESS. 1p36 deletion and 15q duplication occurred most frequently. CNV detection should be performed in patients with IESS of unknown causes, especially in children with craniofacial anomalies and microcephaly. We summarized copy number variants (CNVs) and phenotypes of infantile epileptic spasms syndrome (IESS) in a cohort of 74 patients. 35 CNVs were identified. 11 copy number deletions and 5 copy number duplications have not been reported previously in IESS, including two CNVs have not been reported previously in epilepsy.