Etiologic Classification of 541 Infantile Spasms Cases: A Cohort Study

Pan Peng; Miriam Kessi; Leilei Mao; Fang He; Ciliu Zhang; Chen Chen; Nan Pang; Fei Yin; Zou Pan; Jing Peng

doi:10.3389/fped.2022.774828

Etiologic Classification of 541 Infantile Spasms Cases: A Cohort Study

Front Pediatr. 2022 Mar 7:10:774828. doi: 10.3389/fped.2022.774828. eCollection 2022.

Authors

Pan Peng¹, Miriam Kessi¹, Leilei Mao¹, Fang He¹, Ciliu Zhang¹, Chen Chen¹, Nan Pang¹, Fei Yin^{1

2}, Zou Pan¹, Jing Peng^{1

2}

Affiliations

¹ Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.
² Hunan Intellectual and Developmental Disabilities Research Center, Changsha, China.

Abstract

Objective: To explore the etiology of infantile spasms (IS) in a large Chinese cohort based on the United States National Infantile Spasms Consortium (NISC) classification.

Methods: In the present study, we recruited IS patients diagnosed at a single center (Xiangya Hospital, Central South University) between Jan 2010 and Aug 2019. Thereafter, we collected their clinical and genetic information retrospectively. Their underlying etiologies were classified according to the NISC classification and then compared in different scenarios to understand their distribution.

Results: A total of 541 patients with IS from 18 provinces were included in this study. The underlying etiology was identified in 53.2% of the cases: structural-acquired, 25.3%; genetic, 12.9%; genetic-structural, 7.2%; structural-congenital, 5.0%; metabolic, 2.4%; infections, 0.4% and immune, 0%. Whole-exome sequencing (WES) provided the highest diagnostic yield (26.9%). In structural-acquired IS, the proportion of hypoglycemic brain injuries was significant, second only to hypoxic-ischemic encephalopathy. There was no patient discovered to have Down syndrome. STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL, and TSC1 were the most frequently implicated genes. Genetic causes were found to be the most common cause of IS in the early onset group, while structural-acquired etiologies were common in males and preterm babies. Patients with pre-spasm seizures were associated with a higher proportion of identified causes than those without. Non-acquired structural etiologies were more common in patients without hypsarrhythmia than in those with hypsarrhythmia.

Significance: The most prevalent cause of IS was structural acquired followed by genetic causes. When brain MRI fails to detect the etiology, we propose WES as the next step. Structural-acquired IS and cases with genetic disorders are characteristic of the Chinese cohort, however, the etiology differs with the patient's age of onset, gestation age at birth, sex, and the presence/absence of both pre-spasm seizures, and hypsarrhythmia.

Keywords: etiologies; infantile spasms (IS); spectrum; variants; whole-exome sequencing (WES).