SMC1A-Related Developmental and Epileptic Encephalopathies: A Case Report and Literature Review

“Developmental and epileptic encephalopathies” (DEE) is a recently proposed term to refer to a group of rare and severe neurodevelopmental disorders when patients present both epilepsy and developmental delay. Although the list of DEE–related genes has been rapidly expanded, many of these genes’ genotype-phenotype correlations remain complex and require further data accumulation. As an example, mutations in SMC1A have been lately identified in patients with DEE features but were initially shown to cause another phenotype, Cornelia de Lange syndrome (CdLS). In this study, we report a patient with a novel truncation mutation in the SMC1A gene detected by whole-exome sequencing (WES) confirmed by Sanger sequencing. Furthermore, we review the literature to gain a better understanding of the human clinical spectrum associated with SMC1A mutations as well as the genotype-phenotype correlations of SMC1A in the context of the “epilepsy-dominant” phenotype. Data analysis of our epileptic patient and clinically similar cases published recently reveals that they have a consistent phenotype which can be specified as female-limited DEE with cluster seizures. Also, although SMC1A-related DEE is often caused by truncation mutations, there are some exceptions suggesting that more studies are needed. In conclusion, this study describes a new case of SMC1A-related DEE, a new phenotype of SMC1A being recognized recently. The study also reviews the complex genotype-phenotype relationships of SMC1A in epilepsy and emphasizes that SMC1A is an important gene in female-limitted DEE with cluster seizures.