Genotype-phenotype correlations in DSP-associated arrhythmogenic cardiomyopathy that initially presents as myocarditis: a case report and literature review.

OBJECTIVE: This case report summarizes the clinical characteristics and molecular genetic features of arrhythmogenic cardiomyopathy (ACM) caused by mutations in DSP that initially presented as myocarditis.

METHODS: The clinical manifestations, genetic variation characteristics, and prognosis of a case that presented with an episode of myocarditis and was ultimately diagnosed with ACM caused by compound heterozygous variants in the DSP gene were retrospectively analyzed. Pubmed, Medline, Web of Science, China National Knowledge Infrastructure, and Wanfang Database were searched to summarize the clinical characteristics of ACM caused by mutations in DSP that initially presents as myocarditis and to explore the relationship between genetics and phenotypes.

RESULTS: A 9-year-old female patient was diagnosed with myocarditis due to recurrent dizziness, elevated troponin levels, frequent premature ventricular contractions, and imaging findings. Whole-exome sequencing (WES) identified compound heterozygous variants in the DSP gene (NM_004415.4) in the proband, namely, c.7964C > G and c.6785G > T, which were inherited from her father and mother, respectively. A total of 22 cases with DSP gene mutations were identified, including 13 heterozygous mutations, nine nonsense mutations, six frameshift mutations, five missense mutations, one homozygous mutation, one splice-site mutation, and one with compound heterozygous variants. All the patients were ultimately diagnosed with ACM and initially presented with myocarditis. Troponin levels were elevated in all patients. Electrocardiograms showed abnormalities in all cases, including ST-T changes in nine cases, ventricular tachycardia in seven cases, premature ventricular contractions in two cases, and low voltage in two cases. Echocardiography demonstrated left ventricular structural abnormalities or dysfunction in 13 cases, right ventricular structural abnormalities or dysfunction in one case, and biventricular structural abnormalities or dysfunction in one case.

CONCLUSION: ACM caused by DSP variants often presents with recurrent episodes of myocarditis, accompanied by elevated troponin levels, an abnormal electrocardiogram, and changes in cardiac structure and function. Gene detection results provide a basis for clinical diagnosis. This study found novel compound heterozygous variants in the DSP gene and expanded the clinical feature spectrum of DSP-associated ACM.