Holt-Oram syndrome ... (Holt-Oram syndrome) - Gen TBX5.

Holt Oram syndrome is a disorder characterized by skeletal abnormalities of the hands and arms and heart problems.

People with Holt Oram syndrome have abnormal development of the bones of the upper extremities. Bone abnormalities include abnormalities in the bones of the wrist, the absence of a thumb, a long thumb finger appears, partial or complete absence of the forearm bones, underdevelopment of the humerus and abnormalities of the clavicle or shoulder blades. These skeletal abnormalities may affect one or both of the upper limbs. If both upper limbs are affected, bone abnormalities may be the same or different on each side. In cases where skeletal abnormalities are not the same on both sides of the body, usually the left side is more affected than the right side.

About 75 percent of people with Holt Oram syndrome have heart problems, which can be life threatening. The most common problem is a defect of the interventricular septum and atrial heart. Some people with Oram syndrome Holt- have impaired cardiac conduction caused by abnormalities in the electrical system that coordinates the contractions of the heart chambers, so can cause bradycardia or fibrillation. The features of Oram syndrome Holt are similar to those of a condition called Duane syndrome - radial ray. S owever, these alterations are caused by mutations in different genes.

Holt Oram syndrome is due to mutations in the gene TBX5, located on the long arm of chromosome 12 (12q24.1), which encodes the T -box 5 protein that plays an important role in the formation of tissues and organs during embryonic development. T -box 5 protein is a transcription factor. During embryonic development, the T -box 5 activates genes involved in the normal development of the upper extremities protein. T -box 5 protein also activates genes involved in the growth and development of the heart. This protein appears to be particularly important for the formation of the septum that separates the right and left sides of the heart. T -box 5 protein is also essential for the formation of the electrical system that coordinates the contractions of the heart chambers.

They have identified more than 70 mutations in the gene cause the disease TBX5. Most of these mutations prevent the production of the T -box 5 protein. Other mutations change the amino acids involved in T -box 5 protein. It is believed that an amino acid change impairs the ability of the protein in DNA transfer. As a result, genes that are important for the development of the heart and upper limbs are not activated.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the alteration.

In some cases, an affected person inherits the mutation from an affected parent. Other cases result from new mutations in the gene and occur in people with no history of disease in your family.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Oram syndrome Holt, by complete PCR amplification of the exons of the gene TBX5, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).