Digenic sarcomeric variants in paediatric dilated cardiomyopathy and maternal peripartum cardiomyopathy: a familial case report

Left ventricular non-compaction (LVNC) can be observed as a phenotypic trait in patients with dilated cardiomyopathy. Familial cases have been increasingly recognized, with sarcomeric gene mutations—particularly in MYH7 and MYBPC3—playing a significant role. Peripartum cardiomyopathy (PPCM) may also share overlapping genetic architecture with inherited cardiomyopathies.

We report a 7-year-old girl with a clinical diagnosis of dilated cardiomyopathy with LVNC since infancy. Genetic analysis revealed two heterozygous missense variants in sarcomeric genes associated with inherited cardiomyopathies: MYH7: c.4186C>T (p.Arg1396Trp) and MYBPC3: c.2672G>A (p.Arg891Gln), both classified as variants of uncertain significance. Segregation analysis showed that the MYH7 variant was maternally inherited and the MYBPC3 variant paternally inherited. Notably, the mother developed PPCM 4 months postpartum, with an ejection fraction (EF) of 35%–40%, and was found to carry the same MYH7 variant. The father remained asymptomatic. This case highlights a potential familial cardiomyopathy syndrome with phenotypic variability: the child presenting with an dilated cardiomyopathy with LVNC phenotype and the mother with PPCM. The presence of distinct cardiomyopathy phenotypes within the same family carrying shared and separate sarcomeric variants suggests a possible genotype–phenotype correlation, emphasizing the importance of comprehensive genetic screening and long-term familial surveillance in such cases.

This report highlights the clinical relevance of identifying digenic sarcomeric variants in paediatric cardiomyopathy, particularly when associated with a positive maternal history of PPCM. Familial evaluation and recognition of genotypic overlap may aid in risk stratification and management.