SNP Shot: Genomic Insights

Heterotaxy syndrome is a disorder characterized by the abnormal arrangement of internal organs within the chest and abdomen. The term itself comes from Greek, signifying an "other than" or different "arrangement." Individuals affected by heterotaxy have complex birth defects impacting organs such as the heart, lungs, liver, spleen, and intestines.

Typically, organs in the chest and abdomen occupy specific positions on the right or left side of the body. For instance, the heart, spleen, and pancreas reside on the left, while most of the liver is on the right. This typical arrangement is called "situs solitus." In rare cases, the internal organs are completely flipped, a condition known as "situs inversus," resembling a mirror image. Situs inversus usually poses no health risks unless it's part of a larger syndrome affecting other body parts. Heterotaxy syndrome, also known as "situs ambiguus," represents an organ arrangement that falls somewhere between the typical "situs solitus" and the mirrored "situs inversus." Unlike situs inversus, the atypical organ placement in heterotaxy syndrome often leads to significant health issues.

Heterotaxy syndrome can alter the heart's structure, including the connections of major blood vessels. The lungs can also be affected, with variations in the number of lobes and the structure of the bronchi (airways leading to the lungs). In the abdomen, individuals might have no spleen (asplenia) or multiple, small, poorly functioning spleens (polysplenia). The liver may be positioned across the midline of the body rather than on the right side. Some individuals also experience intestinal malrotation, a twisting of the intestines during early development before birth.

Depending on the affected organs, heterotaxy syndrome can manifest with symptoms like bluish skin or lips (cyanosis, caused by low oxygen levels), breathing difficulties, increased susceptibility to infections, and digestive problems. Critical congenital heart disease, a group of complex heart defects present at birth, often causes the most severe complications. Biliary atresia, a bile duct problem in the liver, can also lead to serious health issues in infancy.

The severity of heterotaxy syndrome varies widely depending on the specific abnormalities present. Some individuals may experience only minor health problems, while others may face life-threatening complications in infancy or childhood, even with medical intervention.

Inheritance:

Most instances of heterotaxy syndrome are sporadic, meaning only one person in a family is affected. However, about 10% of individuals with heterotaxy have a close relative (like a parent or sibling) with a congenital heart defect, but without other typical features of heterotaxy. Isolated congenital heart defects and heterotaxy syndrome may represent a spectrum of manifestations caused by a particular genetic mutation, a concept known as variable expressivity. Alternatively, different genetic and environmental factors might combine to cause isolated heart defects in some family members and heterotaxy syndrome in others. When heterotaxy syndrome is inherited, it can follow an autosomal dominant, autosomal recessive, or X-linked pattern, depending on the gene involved. Autosomal dominant inheritance requires only one copy of the altered gene to cause the disorder. Autosomal recessive inheritance requires mutations in both copies of the gene. Parents of individuals with autosomal recessive conditions each carry one copy of the mutated gene but usually don't show symptoms. In X-linked inheritance, the mutated gene is located on the X chromosome, one of the sex chromosomes. When heterotaxy syndrome is a feature of primary ciliary dyskinesia, it follows an autosomal recessive inheritance pattern.