Holt Oram Syndrome, also known as Heart-Hand Syndrome, is a hereditary condition associated with radial club hand, absent thumb, and heart defects. Individuals with Holt Oram Syndrome will present with abnormally developed bones in their upper extremities. Affected bones may include the wrist bones (carpals), fingers and thumb (metacarpals), the forearm (radius and ulna), the upper arm (humerus), and the collar bone or shoulder blades. These defects may be present in one or both of the upper extremities.
The majority of individuals (75%) with Holt Oram Syndrome have heart defects in addition to deformities of the upper extremities. The most common cardiac problem is a defect in the septum (muscle that separates the two halves of the heart). A hole in the septum is referred to as atrial septal defect (ASD) and ventricular septum defect (VSD) depending on the location of the defect. Some individuals with Holt Oram Syndrome may also have cardiac conduction disease, which is an irregularity of the electrical system that controls heart rate.
Holt Oram Syndrome is quite rare, occurring in 1 in 100,000 individuals. The condition has been linked to mutations in the TBX5 gene. This gene codes for a protein that is involved in the development of the upper limbs and the heart. The condition is inherited in an autosomal dominant pattern. Only one copy of the gene is required to cause the disorder. Individuals may inherit the gene from an affected parent or it may occur as a spontaneous mutation.