Caffey disease ... (Caffey disease) - Gen COL1A1.

Caffey disease, also called cortical hyperostosis child, is a bone alteration occurs most often in newborns and is characterized by hyperostosis. Bone abnormalities mainly affect the jaw, the scapula, the clavicles and the diaphysis. Affected bones can double or triple in width, as shown by x - ray images. In some cases, two bones that are next to each other, as two ribs, the radius and ulna or the tibia and fibula fuse. Moreover, affected newborns have swollen joints and soft tissues, including muscles, pain and redness in the affected areas. Affected children may also have a fever and be irritable.

Signs and symptoms of Caffey disease usually evident in newborns approximately 5 months of age. In rare cases, skeletal abnormalities can be detected by ultrasound during the last weeks of development before birth. For unknown reasons, swelling and pain associated with Caffey's disease usually disappear within a few months. Through bone remodeling, excessive bone is reabsorbed by the body. However, if two adjacent bones have fused, may cause complications. For example, fused rib bones can cause scoliosis or limited chest expansion, which can cause respiratory problems. Most people with Caffey disease are more related problems after early childhood. In some cases, hyperostosis may occur years later. In addition, some adults who had Caffey disease in childhood have other abnormalities of bone and connective tissues. Affected adults may have laxity, skin hyperextensible or hernias.

This process is due to mutations in the COL1A1 gene, located on the long arm of chromosome 17 (17q21.33). This gene encodes a big molecule called type I collagen Collagens are a family of proteins that strengthen and support many body tissues, including cartilage, bone, tendons, skin and sclera. Collagen type I is the most abundant form of collagen in the human body. Specifically, the COL1A1 gene encoding the pro-?1 chain. Collagens begin as procollagen molecules, which must be processed by enzymes outside the cell to remove additional proteins segments end. Each procollagen molecule consists of three chains: two ?1 chains pro (I), which are encoded from the COL1A1 gene and a pro-?2 chain (I), which is encoded COL1A2 gene from. Once these molecules are processed, the collagen molecules are arranged in long thin fibrils. inside these fibrils, individual collagen molecules are crosslinked to each other. These crosslinks result in the formation of collagen fibrils very strong, found in the spaces around the cells.

A mutation in the COL1A1 gene results infantile cortical hyperostosis, commonly known as Caffey disease. The mutation responsible for this disease replaces the amino acid arginine by the amino acid cysteine at position 836 of the protein (Arg836Cys or R836C). This mutation leads to the production of collagen type I fibrils that are variable in size and shape, but it is unknown how these changes lead to signs and symptoms of Caffey disease.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is generally sufficient to express the disease. About 20% of people who have the mutation that causes Caffey disease have no signs or symptoms. This phenomenon is called incomplete penetrance. In some cases, an affected person inherits the mutation that causes the disease Caffey of a 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 Caffey disease by the complete PCR amplification of the exons of the COL1A1 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).