Left Ventricular Noncompaction (LVNC)
Echocardiographic image (4-chamber view) of a patient with typical LVNC morphology (arrows).
Left ventricular noncompaction (LVNC) has recently been classified as a primary cardiomyopathy with a genetic etiology. The echocardiographic characteristics in affected individuals include a severely thickened, two-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses. The clinical features consist of both asymptomatic and symptomatic patients with progressive deterioration of cardiac function. Major complications are congestive heart failure, arrhythmias, thrombembolic events, and sudden cardiac death.
Since 1999 we have been enrolling patients with isolated LVNC to learn more about the genetic etiology of this cardiomyopathy. Using this cohort we have found:
There are both familial and sporadic cases of LVNC. For familial cases, the predominant mode of transmission is autosomal dominant. Detailed pedigree analysis and cardiac evaluation of first-degree family members of affected individuals is therefore recommended.
A novel genetic locus for isolated LVNC on chromosome 11p15. The underlying genetic defect has not yet been identified.
We could recently demonstrate that LVNC is within the diverse spectrum of cardiac morphologies triggered by sarcomere protein gene defects. Heterozygous mutations in LVNC were found in 3 genes: β-myosin heavy chain (MYH7), α-cardiac actin (ACTC), and cardiac Troponin T (TNNT2). Mutations in several sarcomeric protein genes have previously been implicated in familial hypertrophic cardiomyopathy (HCM) and in dilated cardiomyopathy (DCM). Our findings support the hypothesis that there is a shared molecular etiology of different cardiomyopathic phenotypes.
This work is supported by the Deutsche Forschungsgemeinschaft (SA 1389/1-1).
Relevant Publications:
Sasse-Klaassen S, Gerull B, Oechslin E, Jenni R, Thierfelder L (2003) Isolated noncompaction of the left ventricular myocardium in the adult is an autosomal dominant disorder in the majority of patients. Am J Med Genet 119A:162-167
Sasse-Klaassen S, Probst S, Gerull B, Oechslin E, Nürnberg P, Heuser A, Jenni R, Hennies HC, Thierfelder L (2004) Novel gene locus for autosomal dominant left ventricular noncompaction maps to chromosome 11p15. Circulation 109:2720-2723
Klaassen S, Probst S, Oechslin E, Gerull B, Krings G, Schuler P, Greutmann M, Hürlimann D, Yegitbasi M, Pons L, Gramlich M, Drenckhahn JD, Heuser A, Berger F, Jenni R, Thierfelder L (2008) Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation 117:2893-2901
Involved Scientists
Sabine Klaassen, (Postdoc) , Project leader
Susanne Probst (PhD student)
Sigrid Milan (Technician)
For more information contact:
klaassen@mdc-berlin.de