# Case Report: Diverse cardiac and muscular phenotypes in DES c.1024A>G (p.Asn342Asp) variant: a case series with limb weakness as the initial presentation

## TL;DR

Three patients with a DES gene variant showed different muscle and heart symptoms, starting with leg weakness.

## Contribution

Highlights diverse clinical presentations of the DES c.1024A>G variant and proposes management recommendations for desminopathy.

## Key findings

- All three patients had the DES c.1024A>G variant but showed distinct cardiac and muscular symptoms.
- Limb weakness was the initial symptom in all cases, followed by varying heart conditions like heart failure and arrhythmias.
- Phenotypic differences suggest variable expression of the DES variant, requiring tailored management strategies.

## Abstract

We report three patients with bilateral lower limb weakness as the initial symptom. Case 1 presented at 37 years old with bilateral lower limb weakness. The condition gradually worsened, eventually leading to wheelchair dependence. He later sought medical attention for heart failure. Echocardiography showed diffuse left ventricular dysfunction, and the electrocardiogram revealed third-degree atrioventricular block. Case 2 developed bilateral lower limb weakness at 38 years old, with milder symptoms. The main cardiac manifestation was paroxysmal atrial fibrillation. Case 3 presented at 33 years old with lower limb weakness and myalgia, with significant involvement of all four limbs. The primary cardiac finding was left ventricular hypertrophy, and the electrocardiogram showed sinus pauses. Despite the differences in clinical presentations, all three patients were diagnosed with the same DES c.1024A>G (p.Asn342Asp) variant. We discuss the possible factors contributing to the phenotypic differences. Based on the uniqueness of this pathogenic variant site, we propose recommendations for the treatment and management of desminopathy.