Skip to main content

Conference Program

Subpage Hero

Loading

Tetrasomy 9p in a patient affected with dilated cardiomyopathy: incidental finding or extended phenotype? 

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical-Adult
  • Secondary Categories:
    • Clinical-Adult & Pediatric
Introduction
Introduction

Tetrasomy 9p is a rare genetic disorder able to cause embryonic or premature lethality. Affected living patients have wide phenotypic variability that ranges from apparently normal to individuals severely affected with growth retardation, intellectual deficiency, congenital malformations and dysmorphic signs. The two extra copies of chromosome nine short arms are frequently located on an isochromosome, and the imbalance is generally observed in a mosaic state.

Dilated cardiomyopathies, on the other hand, manifest clinically in advanced stages of the disease with heart failure and arrhythmias or conduction anomalies. Multiple genes have been identified as causal for the nonischemic group encompassing the syndromic and the nonsyndromic forms. Tetrasomy 9p however has not been considered before as a syndromic cause for dilated cardiomyopathy.  

We report on a 63-year-old patient affected with dilated cardiomyopathy who was incidentally found to have a mosaic tetrasomy 9p, without any other plausible explanation for her cardiac phenotype after extensive investigations.



 

Case Presentation
Case presentation

The patient was a 63-year-old female at referral to the cardiogenetics clinic for the study of dilated cardiomyopathy of undetermined etiology. She was born with intrauterine growth retardation and showed failure to thrive and myopia during childhood. Her first hospitalization took place at the age of 63 years, due to heart failure and rapid auricular fibrillation associated with severe bradycardia with junctional rhythm. The first Torsade de pointes episode was then documented, as well as left ventricular dysfunction. Subsequently, she was diagnosed with long QT syndrome and a left bundle branch block. A dual-chamber-rate modulated pacemaker was implanted, but following a second Torsade de pointes episode it was replaced with an implantable cardioverter-defibrillator. As the dilated cardiomyopathy became more severe, she needed a V-Wave cardiac device, and she is currently on the waiting list for a heart transplant.

The patient was the third child in a sibship of eight, she had two adult healthy daughters and five grandchildren, without antecedents of pregnancy losses. On physical exam, she was 159.2 cm tall, she had a weight of 78.1 Kg, her body mass index was 30.8 and she had a 52 cm head circumference (1 percentile, -2.2 SD). Dysmorphic signs were present, including microcephaly, low anterior hairline, small narrow forehead, strabismus, deep set eyes, bulbous nose, downslanting lips, high palate with dental malocclusion and macrotia (7 cm). Her fingers were slender, her nails showed vertical lines, and she had a left thoracolumbar scoliosis.

 

Diagnostic Workup
Diagnostic Workup

Tomodensitometry showed a normal brain, as well as an accessory spleen, some bilateral renal cysts and colon diverticulosis. The first molecular test targeting 58 genes associated to dilated cardiomyopathies resulted negative. Another test performed at a different laboratory included 166 genes responsible for cardiac diseases, this time a tetrasomy of the short arm of chromosome 9 was identified, as well as a missense variant of unknown significance in the KCNE1 gene (c.293G>A, p. Arg98Gln) unable to explain the patient’s phenotype. The tetrasomy was confirmed by complete genome hybridization: arr(hg18) 9p24.3q13(2934-70111621)x3-4. GTG-banding karyotyping evidenced the mosaic isochromosome: 47,XX,+i(9)(p10)(27)/46,XX(6), in 82% of the blood cells analysed. Despite the high level of mosaicism in the blood tissue, the patient was not affected with intellectual deficiency or major congenital malformations, allowing for the chromosomal imbalance to remain undiagnosed until now.

 

Conclusion
Conclusions

The etiology of the dilated cardiomyopathy in the patient remains imprecise. All the monogenic causes currently known as potential candidates have been ruled out. Tetrasomy 9p could represent an incidental finding, nevertheless, it should remain in the differential diagnosis until more individuals affected with tetrasomy 9p reach an advanced age and the natural history of this condition is better understood.

Agenda

Sponsors