Arrhytmogenic cardiomyopathy related to CTNNA3 mutation gene: CMR features

Description of Clinical Presentation: A 44-year-old female with no cardiovascular symptoms was referred to our center for cardiovascular magnetic resonance (CMR) following genetic testing that revealed a CTNNA3 gene mutation, known to be associated with right-dominant arrhythmogenic cardiomyopathy.
Given the CMR findings and the autosomal dominant inheritance pattern of the mutation, first-degree relatives were also screened by CMR and exhibited a similarly asymptomatic clinical course, with no reported history of arrhythmias, syncope, or structural heart disease.

Diagnostic Techniques and Their Most Important Findings: The proband, her parents and brother underwent CMR (1.5T Magnetom Avanto Fit scanner). [Figure 1] The acquisition protocol included cineSSFP sequences for functional assessment and strain analysis, Black-blood sequences to detect fatty metaplasia/infiltration, MOLLI sequences for native T1 and Extracellular Volume estimation, T2p-SSFP sequences for T2 mapping, Fast GRE T1 sequences for perfusion and PSIR T1 sequences for late gadolinium enhancement (LGE) detection.

The proband’s CMR showed a focal IndiaInk artifact area in the apex, consistent with fatty metaplasia/infiltration, focal dyskinesia of the distal right ventricular free wall, preserved biventricular function, LGE in the inferior wall and reduced native T1 mapping values. [Figure 2] The proband’s father’s CMR demonstrated a similar small area of IndiaInk artifact in the true apex and LGE in the inferior wall. The proband’s mother’s CMR revealed reduced T1 mapping values. Finally, the proband’s brother’s CMR was unremarkable, with no significant structural or tissue abnormalities detected.

Learning Points from this Case: CTNNA3 mutations may be associated with subtle phenotypic alterations detectable by advanced CMR techniques, even in asymptomatic individuals. CMR tissue characterization, including fat-sensitive sequences, is essential for the early identification of arrhythmogenic substrates, particularly in genotype-positive/phenotype-negative individuals. CMR familial screening in the context of inherited cardiomyopathies can reveal subclinical myocardial involvement, reinforcing its role, also before genetic tests, in early disease detection and risk stratification.

Figure 1. Proband’s family pedigree.
Figure 2. Proband’s CMR. A, CineSSFP sequence showing focal India Ink artifact in the apex (red circle), confirmed by focal hyperintensity in Black-Blood sequence and consistent with fatty metaplasia/infiltration (red circle in B).