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

## TL;DR

A male infant with rare mutations in CACNA1E and FBN1 genes presented with spasms, deformities, and low muscle tone, highlighting the role of whole exome sequencing in diagnosing complex cases.

## Contribution

The paper reports a rare case of dual de novo mutations in CACNA1E and FBN1 genes contributing to a complex neurodevelopmental disorder.

## Key findings

- Whole exome sequencing identified two likely de novo mutations in CACNA1E and FBN1 genes.
- The CACNA1E mutation is consistent with Developmental and Epileptic Encephalopathy-69 (DEE69).
- The FBN1 mutation has implications for long-term cardiovascular health.

## Abstract

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.