Abstract / Summary
Purpose IQ motif and Sec7 domain ArfGEF 2 (IQSEC2)-related encephalopathy is a rare neurodevelopmental disorder characterized by developmental impairment, epilepsy, and behavioral abnormalities. This study investigated the clinical and genetic features of 10 patients with IQSEC2-related encephalopathy treated at a single center in Korea. Methods We retrospectively reviewed the medical records of 10 patients with pathogenic or likely pathogenic IQSEC2 variants. Clinical characteristics, epilepsy phenotypes, neurodevelopmental features, neuroimaging findings, and genetic data were analyzed. Results The cohort included four males and six females, and four variants were novel. The identified variants comprised four nonsense variants, three frameshift variants, one missense variant, one splice-site variant, and one exon deletion. Epilepsy was documented in nine patients, including Lennox–Gastaut syndrome in four, Doose syndrome in one, and nonspecific epilepsy in four; the mean age at seizure onset was 2.4 years. All patients had developmental delay ranging from mild to severe, and developmental delay had been recognized before seizure onset in nine patients. Autism spectrum disorder was documented in four patients, brain magnetic resonance imaging abnormalities in five, scoliosis in four, and precocious puberty in two. Conclusion IQSEC2-related encephalopathy showed a heterogeneous clinical spectrum that included epilepsy, developmental impairment, and variable behavioral and systemic features. The identification of precocious puberty in two patients expands the reported clinical spectrum. Central precocious puberty has rarely been described in patients with IQSEC2-related encephalopathy. Although a direct causal relationship remains unclear, these findings support the need for endocrine surveillance as part of longitudinal care.