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Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation
Aleksandra Nijak1, Maaike Alaerts1, Cuno Kuiperi2
1Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Insights
Genetic analysis identified a TPM1 variant in a family with left ventricular non-compaction and Ebstein anomaly. This finding links TPM1 to this combined cardiac condition, suggesting broader genetic testing is needed.
Area of Science:
- Cardiology
- Genetics
- Developmental Biology
Background:
- Left ventricular non-compaction (LVN(C)) is a rare inherited cardiomyopathy from abnormal heart development.
- It can co-occur with other congenital heart defects like Ebstein anomaly (EA), characterized by tricuspid valve displacement.
Abstract:
Left ventricular non-compaction (cardiomyopathy) (LVN(C)) is a rare hereditary cardiac condition, resulting from abnormal embryonic myocardial development. While it mostly occurs as an isolated condition, association with other cardiovascular manifestations such as Ebstein anomaly (EA) has been reported. This congenital heart defect is characterized by downward displacement of the tricuspid valve and leads to diminished ventricular size and function. In an autosomal dominant LVN(C) family consisting of five affected individuals, of which two also presented with EA and three with mitral valve insufficiency, we pursued the genetic disease cause using whole exome sequencing (WES). WES revealed a missense variant (p.Leu113Val) in TPM1 segregating with the LVN(C) phenotype. TPM1 encodes α-tropomyosin, which is involved in myocardial contraction, as well as in stabilization of non-muscle cytoskeletal actin filaments. So far, LVN(C)-EA has predominantly been linked to pathogenic variants in MYH7. However, one sporadic LVN(C)-EA case with a de novo TPM1 variant has recently been described. We here report the first LVN(C)-EA family segregating a pathogenic TPM1 variant, further establishing the association between EA predisposition and TPM1-related LVN(C). Consequently, we recommend genetic testing for both MYH7 and TPM1 in patients or families in which LVN(C)/non-compaction and EA coincide.