West Syndrome due to ALG13 mutation presenting vigabatrin-associated reversible MRI signal changes and drug-induced dyskinesia

Abstract

Heterozygous mutations in the asparagine-linked glycosylation 13 (ALG13) gene cause a rare genetic disorder that severely affects neurological development. Symptoms associated with ALG13 mutations include severe epilepsy and/or West syndrome (WS). Most cases reported in the literature describe typical characteristics of patients within whom de novo mutations have been identified. A 5-month-old girl with developmental delay and epileptic spasms, without dysmorphic features, is described. Electroencephalography (EEG) showed hypsarrhythmia, compatible with WS, but complementary examinations did not find an underlying etiology. Vigabatrin therapy was started, and then adrenocorticotropic hormone (ACTH) therapy was added. On follow-up, brain magnetic resonance imaging (MRI) revealed restricted diffusions compatible with vigabatrin-associated reversible MRI signal changes. As the spasms and hypsarrhythmia on EEG persisted, a second cycle of ACTH was performed, and then, the patient manifested a hyperkinetic movement, characteristic of drug-induced dyskinesia. Further investigation was carried out, and whole-exome sequencing revealed a de novo pathogenic variant in ALG13 gene. The current case report expands our knowledge of WS by considering a female patient with unspecific clinical features arising from an undefined subjacent etiology. This case also emphasizes the importance of a thorough work-up to determine the underlying genetic etiology and presents the challenges in the diagnostic investigation in clinical practice.