Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation

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 repo...

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Bibliographic Details
Published in:European journal of medical genetics 2018-01, Vol.61 (1), p.8-10
Main Authors: Nijak, Aleksandra, Alaerts, Maaike, Kuiperi, Cuno, Corveleyn, Anniek, Suys, Bert, Paelinck, Bernard, Saenen, Johan, Van Craenenbroeck, Emeline, Van Laer, Lut, Loeys, Bart, Verstraeten, Aline
Format: Article
Language:English
Subjects:
Child, Preschool
Ebstein anomaly
Ebstein Anomaly - genetics
Ebstein Anomaly - pathology
Exome sequencing
Female
Heart Defects, Congenital - genetics
Heart Defects, Congenital - pathology
Humans
Infant
Infant, Newborn
Left-ventricular non-compaction
Male
Mutation, Missense
Pedigree
TPM1
Tropomyosin - genetics
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Summary: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.
ISSN:1769-7212
1878-0849
DOI:10.1016/j.ejmg.2017.10.003