A novel Troponin I mutation associated with severe restrictive cardiomyopathy—a case report of a 27-year-old woman with fatigue

BACKGROUND: Restrictive cardiomyopathy is rare and heterogeneous in origin, clinical manifestation, and prognosis. Familial forms have, amongst others, been associated with mutations in the TNNI3 gene. We present a case of familial restrictive cardiomyopathy associated with a novel TNNI3 mutation including longitudinal follow-up. CASE SUMMARY: A 27-year-old woman was evaluated for fatigue in the context of a family history of sudden cardiac death. Echocardiography was normal except for mild left atrial dilatation. Focused genetic screening, limited to the most common genes associated with cardiomyopathy, was unremarkable in 2006. In biopsy, mild inflammatory cardiomyopathy was diagnosed, and the patient was discharged. Thirteen years later, rapid clinical deterioration occurred in the context of new-onset atrial fibrillation (AF). Echocardiography now showed gross bi-atrial dilatation and evidence of diastolic dysfunction. Based on haemodynamic tracings during angiography, a diagnosis of restrictive cardiomyopathy was made. In 2018, next-generation sequencing revealed the hitherto undescribed Troponin I variant Lys193Glu in a functionally critical domain. Haemodynamic stabilization was achieved by pulmonary vein isolation. Until now, the patient remains symptom free under diuretic treatment. DISCUSSION: Diagnosis of restrictive cardiomyopathy is complicated by often oligosymptomatic early presentation and a diverse clinical picture. Thorough medical and family history and early invasive haemodynamic tracing are indispensable in diagnosis. Therapy-refractory AF should raise suspicion. Reporting of longitudinal follow-up cases is essential to better understand the early symptoms, development, and prognosis of this rare disease. Broad genetic testing in unclear cases has become more available and affordable and should be considered early in the diagnostic workflow.