Acromícrica dysplasia (Acromicric dysplasia) - Gen FBN1.
The acromícrica dysplasia is a rare bone dysplasia characterized by short stature, short hands and feet, mild facial dysmorphism and radiologic abnormalities features hands. Affected newborns are of normal height but, over time, slow growth leads to short stature. Similarly, the long bones of the arms and legs, and bones of the hands and feet are shorter than expected for the height of the person. Other skeletal features that occur in this disease include delayed bone age, hip dysplasia, abnormally shaped vertebrae and limited movement of joints. Often, affected individuals develop carpal tunnel syndrome. These bone and joint problems may require treatment and those most affected have some limitations in their activities. Other signs and symptoms may include additional round face, well - defined eyebrows, long eyelashes, a bulbous nose with nostrils up, philtrum and a small mouth with thick lips. These facial differences become less noticeable in adulthood. Intelligence is not affected and life expectancy is usually normal.
This process is due to mutations in the FBN1 gene, located on the long arm of chromosome 15 (15q21.1). This gene encodes fibrillin-1 protein. This protein is transported to the outside of cells in the extracellular matrix. In this matrix molecules fibrillin-1 adhere to each other and with other proteins to form microfibrils. The microfibrils are elastic fibers, allowing the skin, ligaments and blood vessels stretch. Microfibrils also provide more rigid support to tissues such as bone and tissues supporting the nerves, muscles and the ocular lens. Microfibrils store a protein called transforming growth factor beta (TGF-?), a critical growth factor. TGF-? affects the development, helping to control the growth and proliferation, differentiation, motility and apoptosis.
They have identified at least 9 mutations in the gene FBN1 in people with acromícrica dysplasia. Genetic mutations are found in exons 41 and 42 the FBN1 gene, and change individual amino acids in a region of fibrillin-1 protein called TGF-? binding protein - like domain 5. These genetic changes lead to a reduction and disorganization microfibrils. Without sufficient to store microfibrils normal TGF-?, the growth factor is abnormally active. These effects probably contribute to physical anomalies that occur in the acromícrica dysplasia, but the mechanisms remain unclear. It is unknown why mutations FBN1 gene associated with acromícrica dysplasia leading to short stature, while other mutations FBN1 also increase the activity of TGF-? result in a condition called Marfan syndrome, characterized by tall .
The acromícrica dysplasia is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease. However, most cases are due to new mutations in the gene and occur in people with no history of disease in your family. In other cases, an affected person inherits the mutation from an affected parent.
Tests in IVAMI: in IVAMI perform detection of mutations associated with acromícrica dysplasia, by complete PCR amplification of the exons of the FBN1 gene, and subsequent sequencing. The most frequent mutations are in exons 41 and 42, so we offer the possibility of starting the test with these exons and, if found, must not continue studying the other 63 exons, with the consequent reduction completion time and cost.
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).