Expert Reviewed By: Dr. Brandon Colby MD
Left ventricular noncompaction (LVNC) is a rare genetic disorder characterized by a poorly compacted and spongy appearance of the left ventricular myocardium, which can lead to various cardiac complications. Understanding, diagnosing, and using genetic testing for LVNC is crucial for early detection, management, and prevention of complications. In this article, we will explore the genetic basis of LVNC, its diagnosis, and the role of genetic testing in this disorder.
Understanding the Genetic Basis of LVNC
Recent studies have shed light on the genetic underpinnings of LVNC, revealing complex gene-disease relationships and molecular pathways implicated in its pathogenesis. Notably, research has graded the strength of gene-disease relationships for genes associated with LVNC, identifying key genetic factors involved in its development.
One such genetic factor is the MYH7 gene, which has been found to harbor a novel heterozygous missense variant associated with LVNC. This variant likely causes actin-myosin binding defects during ventricular wall morphogenesis, contributing to the characteristic noncompaction phenotype.
Furthermore, a systematic large-scale assessment of the genetic architecture of LVNC has discovered substantial genetic overlap with dilated and hypertrophic cardiomyopathies, as well as distinct noncompaction and arrhythmia etiologies. This highlights the diverse genetic landscape of LVNC and its potential shared pathogenesis with other cardiac disorders.
Diagnosing LVNC in Children
Diagnosing LVNC in children can be challenging due to its variable clinical presentation. A study investigating the clinical characteristics and genetic profiles of children with LVNC found heart failure and arrhythmias to be common, while thromboembolic events and genetic syndromes were rare. This highlights the importance of considering LVNC in the differential diagnosis of children presenting with cardiac symptoms, even in the absence of other typical features.
Uses of Genetic Testing in LVNC
Confirming Diagnosis
Genetic testing plays a crucial role in confirming the diagnosis of LVNC, especially in cases with atypical clinical presentations. By identifying pathogenic variants in genes associated with LVNC, genetic testing can provide definitive evidence of the disorder and help guide appropriate management strategies.
Identifying At-Risk Family Members
As a genetic disorder, LVNC can be inherited in an autosomal dominant or autosomal recessive manner. Genetic testing can help identify at-risk family members who may be carriers of pathogenic variants, allowing for early detection and intervention to prevent complications.
Guiding Prognosis and Management
Genetic testing can also aid in predicting the clinical course and prognosis of LVNC, as certain genetic variants may be associated with more severe phenotypes or complications. This information can help guide personalized management strategies, including pharmacological therapy, device implantation, or even heart transplantation in severe cases.
Uncovering Overlapping Cardiomyopathies
Given the genetic overlap between LVNC and other cardiomyopathies, genetic testing can help uncover coexisting cardiac disorders that may require additional management strategies. Identifying these overlapping conditions can help optimize patient care and improve long-term outcomes.
In conclusion, understanding the genetic basis of left ventricular noncompaction 3 is vital for accurate diagnosis and effective management of this rare cardiac disorder. Genetic testing plays a significant role in confirming diagnosis, identifying at-risk family members, guiding prognosis and management, and uncovering overlapping cardiomyopathies. As research continues to unravel the complex genetic landscape of LVNC, we move closer to developing targeted therapies and improving the lives of those affected by this condition.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)