Congenital contractural arachnodactyly; Beals-Hecht syndrome (Congenital contractural arachnodactyly, Beals-Hecht syndrome) - Gen FBN2
Congenital contractural arachnodactyly, also known as Beals-Hecht syndrome of, is a disorder that affects many parts of the body. People with this disorder are usually tall with long limbs (dolichostenomelia) and fingers and long, thin feet (arachnodactyly). Often they have joint contractures that may restrict the movement of your hips, knees, ankles and elbows. Additional features of the contractural arachnodactyly congenital syndrome may include underdeveloped muscles, kyphoscoliosis, camptodactilia, ears that look "wrinkled" and pectus carinatum. Rarely, affected individuals have heart defects, such as dilation of the aortic root or mitral valve prolapse. The life expectancy of people with congenital arachnodactyly contractural varies depending on the severity of the symptoms, but does not have to be shortened. A rare and severe form of contractural arachnodactyly congenital anomalies involves both the heart and the digestive system, in addition to those described skeletal features, in which case those afflicted with this severe form usually do not live beyond infancy.
This syndrome is due to mutations in FBN2 gene located on the short arm of chromosome 5 (5q23.3) encoding fibrillin-2 protein. This protein is transported to the outside of cells to the extracellular matrix, where it binds to other proteins to form microfibrils. Microfibrils become part of the elastic fibers that provide consistency and flexibility to the connective tissue found around joints and organs of the body, and allow the stretching of the skin, ligaments and blood vessels. Furthermore, microfibrils proteins have transforming growth factor beta (TGF-beta) are kept inactive. When released microfibrils, growth factors allow the growth and repair of tissues throughout the body.
They have identified more than 20 mutations in the gene FBN2 in people with congenital contractural arachnodactyly. Most of these mutations in the fibrillin substituted amino-2 protein, usually cysteine amino acid substitution, a different amino acid, which would alter the structure or function of fibrillin-2. All these mutations reduce the amount of fibrillin-2 available to form microfibrils. The decreased formation of microfibrils weaken elastic fibers and cause an overactivation of the growth factors TGF-beta, leading to signs and symptoms of congenital contractural arachnodactyly.
Congenital contractural arachnodactyly is inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the disease. In some cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with congenital arachnodactyly contractural (Beals-Hecht syndrome), by complete PCR amplification of exons FBN2 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).