The link between acute myocarditis (AM) and familial cardiomyopathies (CM) remains unclear.

To assess the clinical significance of AM in families with CM.

We describe the pedigree of 6 families with at least one case of AM and a familial history of CM or sudden death (SD). AM was defined as an infarct-like clinical presentation with normal coronary arteries and myocardial inflammation (MI) documented by cardiac magnetic resonance (CMR), or as an autopsy proven AM.

In family 1 to 5, genetic testing was triggered by the association of a documented case of AM with an index case of CM or early SD. In this setting, all genetic testing revealed a mutation in the desmoplakin (DSP) gene. In family 1, patient II.1 (15 y.o) was diagnosed with AM 6 months after his 12 y.o sister's SD. In family 2, patient II.4 (17 y.o) was diagnosed with AM. His mother had a DCM, with a CMR revealing the presence of MI. In family 3, patient IV.3 (22 y.o) died suddenly from an AM, attested by post-mortem autopsy. Her aunt had a DCM. In family 4, patient II.4 (41 y.o) had an AM, progressing toward a DCM. Her mother had died suddenly at the age of 39, and her niece had a DCM. In family 5, patient V.16 (9 y.o) presented 4 recurrent episodes of AM. Her cousin's mother had a DCM. In family 6, patient IV.3 had 3 episodes of AM, his father had previously been diagnosed with an arrythmogenic right ventricular cardiomyopathy (ARVC) with a desmoglein 2 (DSG2) mutation (Table 1, Fig 1).

AM is strongly associated to desmosomal mutations when a familial history of cardiomyopathy is present, particularly in DSP gene. In these families, DCM phenotype and SD are frequent, and a notable proportion of isolated LGE suggestive of myocardial fibrosis is present in asymptomatic relatives. These results highlight the need for a comprehensive familial screening in case of AM.