The Effect of Genotype Differences on Cardiac Involvement in Cases Diagnosed with Duchenne Muscular Dystrophy
Gizem Doğan1, Gamze Sarıkaya Uzan1, Yiğithan Güzin1
1Department of Pediatric Neurology, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Türkiye.
Insights
Genetic analysis in Duchenne muscular dystrophy (DMD) patients did not reveal a clear link between specific genotypes and cardiac involvement. Further research is needed to understand genotype-phenotype correlations in DMD cardiac complications.
Area of Science:
- Pediatric Cardiology
- Genetics
- Neuromuscular Disorders
Background:
- Duchenne muscular dystrophy (DMD) is a common childhood neuromuscular disease.
- Cardiac involvement significantly impacts morbidity and mortality in DMD patients.
- Prior studies suggest varying effects of different exon mutations on cardiac health.
Purpose of the Study:
- To investigate the relationship between genetic mutations (genotype) and cardiac involvement in DMD patients.
- To analyze how different mutation types and locations influence cardiac manifestations.
Main Methods:
- Retrospective analysis of 120 male DMD patients.
- Genetic analysis to identify mutation types (deletions, mutations, duplications) and locations.
- Cardiac assessment including ejection fraction, fractional shortening, and electrocardiography.
Main Results:
- Deletions were the most common genetic finding (76.7%).
- Cardiac involvement was observed in 12.5% of patients, with onset typically after age 10.
- While no significant difference in mutation type/location and age of cardiac involvement was found, increased left ventricle posterior wall thickness was noted in the exon 44-54 mutation group.
Conclusions:
- This study did not establish a clear correlation between specific genotypes and cardiac involvement in DMD.
- Findings align with existing literature suggesting a complex, not fully understood, relationship.
- Further investigation is warranted to elucidate genotype-phenotype correlations in DMD cardiac disease.
Aim:
Duchenne muscular dystrophy (DMD) is the most frequently seen muscular disease in childhood. Cardiac involvement is extremely important in terms of morbidity and mortality in these patients. Different studies have shown that mutations occurring in various exons are cardioprotective or increase cardiac involvement in DMD cases. The aim of this study was to examine the effect of genotype differences on cardiac involvement in patients diagnosed with DMD with genetic analysis.
Methods:
A retrospective analysis of DMD patients followed up in the Muscle Diseases Centre of Health Sciences University Izmir Tepecik Training and Research Hospital was done.
Results:
Evaluation was made of 120 male DMD patients with a mean age of 9.66 ± 5.10 years. According to the genetic analysis results, 76.7% deletions, 15.8% mutations, and 7.5% duplications were determined. Of the mutations determined, 65.8% were between exons 44 and 54, 17.5% between exons 1 and 18, and 9.2% between exons 19 and 43, 5.8% were non-sense mutations, and 1.7% were on exons >54. In the cases determined with cardiac involvement, the mean age of onset was 11.87 ± 3.11 years. When ejection fraction (EF) <56% or fractional shortening (FS) <28% was accepted as systolic dysfunction cardiac effect, 12.5% of the cases were determined with cardiac involvement. Of the cases determined with cardiac effects, 86.7% were aged >10 years. Electrocardiography was evaluated as normal in 54.5%, sinus tachycardia in 24.2%, short PR in 15.2%, and right and left ventricle hypertrophy in 8.1%. No statistically significant difference was determined in mutation types and location according to the age of cardiac involvement. The left ventricle (LV) posterior wall thickness value determined in the exon 44-54 group was higher than in DMD cases with other mutations. Although not statistically significant, an important result was that the LV posterior wall and IVSed values were evaluated to be high.
Conclusion:
The current study results and findings in literature have not found a clear relationship between genotypes and cardiac involvement in DMD cases.
