What Causes Hypoplastic Left Heart Syndrome?

The causes of hypoplastic left heart syndrome (HLHS) remain elusive. There isn’t a single gene dysfunction that can point to it or a maternal behavior that will always predict it. Generally, physicians believe HLHS is caused by numerous factors. These may include inheritance, gender, presence of other syndromes, and occasionally, maternal behavior.

While the fetus is developing, the direct cause of HLHS is thought to be a structural malformation and underdevelopment of the heart's left side, including the ventricle, atria, and the aortic and mitral valves. Some physicians believe that this process may begin as early as the eighth week of fetal life. One theory is that the mitral valve and aorta develop improperly and block bloodflow to the left atrium and ventricle. Without nutrient-rich blood, these structures cannot grow.

The reason for the initial abnormalities isn’t explained, which means the underlying cause of this condition is still mysterious. In recent years, some research has suggested a link between minor left-sided heart defects, particularly of the aorta, and a greater risk for HLHS. The condition might be more likely to occur in children with parents, aunts or uncles, or grandparents who have left-sided defects. Researchers also know that parents with one child with HLHS are more likely to have another child with the condition.

An additional factor that seems to be a partial cause of hypoplastic left heart syndrome is gender. Boys have this condition more often than girls, and they may account for about 75% of all HLHS cases. This suggests that gender alone may increase risk.

A few genetic conditions are associated with HLHS. These include Holt-Oram, Turner, and Noonan syndromes. Such conditions don’t consistently present with an undersized left side of the heart, however, and they might cause other heart defects.

While no single maternal behavior is identified as a cause of hypoplastic left heart syndrome, there are some things that may increase risk for all heart defects. Use of certain illegal or prescribed drugs has been shown to elevate chances of abnormal fetal heart development. Failure to take folic acid prior to conception and in early pregnancy is now also reliably linked to greater likelihood of heart defects.

In spite of these known potential causes, it’s not that unusual for a baby to be born with HLHS without possessing any risk factors for the condition. When this occurs it underscores the belief that the cause of hypoplastic left heart syndrome is multifactorial. In other words, it arises from numerous causes.

Researchers have not yet discovered the exact combination of factors responsible for HLHS, and it’s possible there may not be one. The condition is always fatal without surgical intervention, which is typically undertaken in the first few days of life. HLHS is not presently curable, but a series of staged surgeries or a heart transplant can extend life for years.