Subclinical myocardial dysfunction is revealed by speckle tracking echocardiography in patients with Cornelia de Lange syndrome

Int J Cardiovasc Imaging. 2022 Nov;38(11):2291-2302. doi: 10.1007/s10554-022-02612-0. Epub 2022 May 19.

Abstract

This study assesses a possible cardiac dysfunction in individuals with Cornelia de Lange syndrome (CdLS) without diagnosed congenital heart disease (CHD) and its association with other factors. Twenty patients and 20 controls were included in the study divided into three age-dependent groups (A: < 10 yrs, B: 10-20 yrs, C: > 20 yrs), and were evaluated using conventional echocardiography, tissue doppler imaging (TDI), two-dimensional speckle tracking and genetic and biochemical analyses. The left ventricular global longitudinal strain (GLS) was altered (< 15.9%) in 55% of patients, being pathological in the older group (A: 19.7 ± 6.6; B: -17.2 ± 4.7; C: -13.6 ± 2.9). The speckle tracking technique revealed a downward trend in the values of strain, strain rate and velocity, especially in the oldest group. Likewise, the ejection fraction (LVEF) and shortening fraction (LVFS) values, although preserved, also showed a decreased with age (p < 0.05). The analytical markers of cardiovascular risk and cardiac function showed no alterations. The molecular analyses revealed 16 individuals carrying pathogenic variants in NIPBL, two with variants in SMC1A, one with a variant in RAD21 and one with a HDAC8 variant. This is the first systematic approach that demonstrates that individuals with CdLS may present early cardiomyopathy, which can be detected by speckle tracking technique even before the appearance of clinical symptoms and the alteration of other echocardiographic or analytical parameters. For all these reasons, cardiological followup is suggested even in the absence of CHD, especially from adolescence onwards.

Keywords: Cornelia de; Echocardiography; Lange syndrome; Myocardial dysfunction; NIPBL; Speckle tracking; Strain.

MeSH terms

  • Adolescent
  • Cardiomyopathies*
  • Cell Cycle Proteins / genetics
  • Child
  • De Lange Syndrome* / diagnostic imaging
  • De Lange Syndrome* / genetics
  • Echocardiography / methods
  • Heart Defects, Congenital*
  • Histone Deacetylases
  • Humans
  • Predictive Value of Tests
  • Repressor Proteins
  • Stroke Volume

Substances

  • HDAC8 protein, human
  • Histone Deacetylases
  • Repressor Proteins
  • NIPBL protein, human
  • Cell Cycle Proteins