SNP Shot: Genomic Insights

Holt-Oram syndrome is a condition defined by deformities in the bones of the upper limbs (hands and arms) and the presence of heart defects.

Individuals affected by Holt-Oram syndrome exhibit unusual bone development in their arms and hands. A common finding is at least one abnormality in the wrist bones (carpal bones), often detectable through x-ray imaging. Additional skeletal issues may include a missing thumb, a thumb that resembles a finger in length, a partial or complete lack of forearm bones, an underdeveloped upper arm bone, and deformities of the collarbone or shoulder blades. These skeletal abnormalities can occur in one or both arms. When both arms are affected, the bone deformities may be identical or different on each side. If the deformities differ between the two sides, the left arm is typically more severely affected than the right.

Approximately three-quarters of individuals with Holt-Oram syndrome experience heart problems, which can be serious and potentially life-threatening. The most frequent issue is a defect in the septum, the muscular wall dividing the heart's right and left sides. A hole in the septum between the upper heart chambers (atria) is known as an atrial septal defect (ASD), while a hole in the septum between the lower chambers (ventricles) is termed a ventricular septal defect (VSD). Some individuals with Holt-Oram syndrome may also have cardiac conduction disease, arising from abnormalities in the heart's electrical system that regulates heart chamber contractions. This can lead to a slow heart rate (bradycardia) or rapid, uncoordinated heart muscle contractions (fibrillation). Cardiac conduction disease can occur with other heart defects (like ASD or VSD) or as the only heart problem in people with Holt-Oram syndrome.

The symptoms of Holt-Oram syndrome are similar to those seen in Duane-radial ray syndrome. However, these two conditions are caused by mutations in different genes.

Inheritance:

Holt-Oram syndrome follows an autosomal dominant inheritance pattern. This means that having only one copy of the mutated gene in each cell is enough to cause the condition.