A Rare Case of Dual De Novo Mutations Presenting With Infantile Spasms, Congenital Contractures, and Axial Hypotonia

This report presents the case of a male infant with a complex neonatal course marked by congenital hand and foot deformities, axial hypotonia, and subsequent development of treatment-resistant infantile spasms. Despite extensive initial investigations yielding normal results, including a normal brain magnetic resonance imaging (MRI), whole exome sequencing (WES) revealed two distinct, likely de novo, autosomal dominant mutations: a pathogenic variant in the CACNA1E gene, consistent with Developmental and Epileptic Encephalopathy-69 (DEE69), and a likely pathogenic variant in the FBN1 gene, an incidental finding with significant implications for long-term cardiovascular health. This case highlights the diagnostic power of WES in complex neurodevelopmental disorders and underscores the challenges in managing multifactorial presentations.