Crouzon with acanthosis nigricans syndrome ... (Crouzonodermoesquelético) (Crouzonodermoskeletal syndrome) - Gen FGFR3.
Crouzon syndrome with acanthosis nigricans, also called dermoesquelético Crouzon syndrome, is a disorder characterized by craniosynostosis during development and acanthosis nigricans. Some of the signs and symptoms of Crouzon syndrome with acanthosis of acantosis overlap with those of Crouzon syndrome. Common characteristics include premature fusion of the skull bones, affecting the shape of the head and face in the whole, prominent eyes because the eye sockets are shallow, strabismus, a small pointy nose, and underdeveloped upper jaw. People with Crouzon syndrome or dermoesquelético Crouzon syndrome usually have normal intelligence.
Several features differentiate the Crouzon syndrome dermoesquelético of Crouzon syndrome. For example, people with Crouzon syndrome have dermoesquelético acanthosis nigricans and subtle changes in the vertebrae. In addition, cementomas may develop in the jaw during adulthood.
This process is due to mutations in the FGFR3 gene, located on the short arm of chromosome 4 (4p16.3). This gene encodes a protein called receptor 3 fibroblast growth factor. This protein is part of a family of receptors of fibroblast growth factor that share similar structures and functions. These proteins play a role in several important cellular processes, including the regulation of growth and cell division, determining the cell type, the formation of blood vessels, healing of wounds and development before birth. The FGFR3 protein is placed across the cell membrane, so that one end of the protein remains inside the cell and the other end remains on the outer surface. This positioning of the protein allows it to interact with specific growth factors outside the cell and receive signals that control growth and development. When these growth factors bind to the FGFR3 protein, protein triggers a cascade of chemical reactions within the cell that instruct to perform certain changes, such as maturation assume specialized functions. Several isoforms of the FGFR3 protein are encoded from the FGFR3 gene. Different isoforms are found in various tissues of the body and interact with a variety of growth factors. Many isoforms are found in the cells that form bones. It is believed that bone cells, the protein FGFR3 regulates bone growth by ossification, particularly in the long bones. One particular isoform of FGFR3 protein is specifically in epithelial cells, including the cells that form the epidermis.
It has identified a single mutation of the FGFR3 gene in people with Crouzon syndrome with acanthosis nigricans. This genetic change replaces the amino acid alanine for glutamic acid amino acid at position 391 of FGFR3 (Ala391Glu or A391E) protein. Although the modified receptor appears to alter the normal growth of the skull bones and affect pigmentation of the skin, it is not clear how this mutation leads to the signs and symptoms of this disease.
Crouzon syndrome with acanthosis nigricans is inherited as an autosomal dominant, 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. Most often, this disease is due to 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 Crouzon syndrome with acanthosis nigricans, by complete PCR amplification of the exons of the FGFR3 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).