Liebenberg syndrome ... (Liebenberg syndrome) - Gen pitx1

Liebenberg syndrome, also known as brachydactyly with joint dysplasia or dysplasia brachydactyly elbows and wrists, is a condition characterized by abnormal development of the upper extremities. In those affected, bone and other tissues in the elbows, forearms, wrists and hands have characteristics related structures in the lower extremities. For example, bones elbows are formed abnormally, which affects the mobility of joints. Rigid elbows act more like knees and can not be rotated as freely as they normally do elbows. The wrist bones are fused, forming structures that resemble the ankles and heels, causing a radial deviation. The metacarpals are longer than normal and fingers are short, similar to the proportions of the bones found in the feet. In addition, the muscles and tendons that are normally only in the hands and feet are absent in people with Liebenberg syndrome. Affected individuals also have joint deformities that limit the movement of the elbows, wrists and hands. The development of the lower extremities is normal in those affected. Individuals with Liebenberg syndrome have no other health problems related to this condition, and life expectancy is normal.

The Liebenberg syndrome is due to genetic changes near PITX1 (paired homeodomain like 1) gene, located on the long arm of chromosome 5 (5q31.1), encoding a protein that plays a critical role in the development of the lower extremities. The PITX1 protein is found primarily in the legs and feet in development. The protein acts as a transcription factor, meaning that binds to specific DNA regions and helps control the activity of particular genes. Specifically, PITX1 regulates the activity of genes that direct the form and structure of the tissues of the lower extremities, including the bones, muscles and tendons. The PITX1 protein is also found in the pituitary gland and developing the gill arches. The PITX1 protein may play a role in the formation of the pituitary gland and branchial derived tissues such as the palate arch, mandible and parts of the inner ear.

Involved genetic changes syndrome Liebenberg deleted, inserted, or rearrange the genetic material near the PITX1 gene. These changes affect DNA regulatory elements, known as enhancers or repressors, which help activate or silence genes. It is believed that the mutations responsible for the development of Liebenberg syndrome relocated enhancers that promote the activity of the genes involved in the development of the upper limb to be closer to the PITX1 gene. Alternatively, mutations can eliminate repressor normally deactivate the PITX1 gene during development of the upper extremities. Consequently, the PITX1 gene is abnormally active during development of the upper extremities. Because the PITX1 protein normally directs the structure of the lower limbs, bones, muscles and tendons develop more in the arms and hands when compared with the legs and feet, leading to the characteristics of the syndrome Liebenberg.

This process is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In most cases, an affected person has a parent with the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Liebenberg, by complete PCR amplification of exons PITX1 gene 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).