Authors :
Presenting Author: Miaomiao Cheng, PhD – Peking University First Hospital, Beijing, China
Ling Bai, Phd – Beijing USCI Medical Laboratory Co., Ltd, Beijing, China; Ying Yang, Phd – Peking University First Hospital, Beijing, China; Wenwei Liu, Phd – Peking University First Hospital, Beijing, China; Xueyang Niu, Phd – Peking University First Hospital, Beijing, China; Yi Chen, Phd – Peking University First Hospital, Beijing, China; Quanzhen Tan, master – Peking University First Hospital, Beijing, China; Xiaoling Yang, Phd – Peking University First Hospital, Beijing, China; Qixi Wu, Phd – Beijing USCI Medical Laboratory Co., Ltd, Beijing, China; Han-Qing Zhao, Phd – Beijing USCI Medical Laboratory Co., Ltd, Beijing, China; Yuehua Zhang, Phd – Peking University First Hospital, Beijing, China
Rationale:
This study aims to summarize the spectrum of copy number variants (CNVs) and the phenotypes of infantile epileptic spasms syndrome (IESS) in a Chinese cohort.
Methods:
The CNVs of children with IESS were identified by genomic copy number variation sequencing (CNV-seq). The CNVs and clinical data of IESS patients were analyzed.
Results:
Seventy four IESS children with pathogenic or likely pathogenic CNVs were enrolled. Thirty five kinds of CNVs were identified: 11 copy number deletions (1p21.3p13.3del, 1q21.1q21.2del, 4q21.21q22.1del, 6q21q22.1del, 9p24.3p23del, 11q23.3q25del, 14q32.33del, 16p13.3del, 22q11.21q11.21del, Xp22.2p22.3del, Yq11.221q12del) and 5 copy number duplications (5p13.2p13.1dup, 18q12.3q21.1dup, 22q11.21dup, X p11.4p11.23dup, and Xq25q25 dup) have not been reported previously in IESS, including 2 CNVs (11q23.3q25del and 18q12.3q21.1dup) have not been reported previously in epilepsy. 87.8% patients were de novo CNVs, 9.5% were inherited from the mother ,and 2.7% were inherited from the father. Mosaicism occurred in one patient with Xq21.31q25 duplication. 16.2% patients were 1p36 deletion and 20.3% were 15q11-q13 duplication. The age of seizure onset ranged from one day after birth to 24 months (medium: five months). Seizure types included epileptic spasms (n =74), focal seizures, tonic seizures, and myoclonic seizures. All patients displayed developmental delay. Additional features included craniofacial anomaly, microcephaly, congenital heart defects, hearing abnormalities, congenital cataracts, and hemangioma. Neuroimaging was abnormal in 55.4% of patients. The last follow-up age ranged from six months to 10 years, 2 months, and 29.7% of patients were seizure-free for more than 12 months with anti-seizure medications.
Conclusions:
Copy number variation is an important etiology of IESS. 1p36 deletion and 15q duplication occurred more frequently in IESS. CNV detection should be done in IESS patients with unknown causes, especially in children with the craniofacial anomaly, microcephaly, and congenital heart defects.
Funding:
Beijing Natural Science Foundation (No. 7222240); Key Research Project of the Ministry of Science and Technology of China (2016YFC0904400 and 2016YFC0904401).