SNP Shot: Genomic Insights

Left ventricular noncompaction (LVNC) is a heart muscle disorder where the left ventricle, the heart's main pumping chamber, doesn't develop normally. Instead of being smooth and compact, the muscle is thickened and has a spongy appearance. This abnormal muscle is weaker and less efficient at pumping blood because it may not contract or relax completely. Proper heart function depends on the full contraction and relaxation of the heart muscle.

The symptoms of LVNC vary. Some individuals have no symptoms, while others experience serious heart problems, including sudden cardiac death. Other symptoms can include blood clots, irregular heartbeats (arrhythmias), palpitations (a fluttering or pounding sensation in the chest), extreme fatigue during exercise (exercise intolerance), shortness of breath (dyspnea), fainting (syncope), leg swelling (lymphedema), and difficulty lying flat. Some individuals may also have other heart defects. LVNC can be diagnosed at any age. About two-thirds of those with LVNC will develop heart failure.

Inheritance:

LVNC can be inherited in several ways. Autosomal dominant inheritance is the most common pattern, often linked to variations in the MYH7 or MYBPC3 genes. This means that only one copy of the altered gene is needed to cause the condition. In many cases, an affected person inherits the altered gene from a parent who also has the condition. Sometimes, the altered gene appears for the first time in the affected person. In these situations, the condition is caused by a new (de novo) variant in the gene and occurs in people with no family history of the disorder.

Less commonly, LVNC follows an autosomal recessive inheritance pattern, where both copies of the relevant gene must be altered to cause the disorder. In these cases, both parents carry one copy of the altered gene but usually don't show symptoms themselves.

LVNC can also be inherited in an X-linked recessive pattern. Some genes associated with LVNC, such as TAFAZZIN, are located on the X chromosome. Males, with only one X chromosome, will develop the condition if they inherit one altered copy of the gene. Females, with two X chromosomes, typically need to inherit two altered copies of the gene to be affected. Therefore, X-linked recessive disorders are much more common in males than in females. A key characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.