Cardiofaciocutaneous skin syndrome ... (Cardiofaciocutaneous syndrome) - Genes BRAF, KRAS, MAP2K1 and map2k2.
The cardiofaciocutaneous Cutaneous (CFC) syndrome is a multisystem congenital disorder characterized by its association with several characteristic abnormalities (heart, facial and ectodermal) and mental retardation. The most common cardiac abnormalities include pulmonary stenosis, hypertrophic cardiomyopathy and atrial septal defects. Among the highlights ectodermal thinning hair, dry and rough skin, palms and soles of the feet shriveled, decreased or absent eyelashes and eyebrows, and the existence of hyperkeratotic skin lesions. For its part, the characteristic facial features include a high forehead that narrows at the temples, short nose, ocular hypertelorism, corners of his eyes directed downward, ptosis, a small chin, broad face and to start, and ears implementation low. Generally, infants have hypotonia, feeding difficulties and growth retardation. Other additional signs and symptoms in children and adults can include macrocephaly, short stature, vision problems and seizures.
Signs and symptoms of cardiofaciocutaneous Cutaneous syndrome significantly overlap with two other genetic alterations, Costello syndrome and Noonan syndrome. All three diseases are distinguished by their genetic cause and some specific signs and symptoms. Unlike Costello syndrome, which significantly increases the risk of developing cancer, cancer does not appear to be an important feature of Cardio-Facio-Cutaneous syndrome.
The cardiofaciocutaneous Cutaneous syndrome may be due to mutations in several genes. Mutations in the BRAF gene, located on the long arm of chromosome 7 (7q34) represent between 75% and 80% of all cases. Mutations in genes MAP2K1, located on the long arm of chromosome 15 (15q22.1 - q22.33) and map2k2, located on the short arm of chromosome 19 (19p13.3) represent between 10% and 15% . Changes in the KRAS gene, located on the short arm of chromosome 12 (12p12.1), constitute less than 5% of cases.
These genes encode proteins which act together to transmit chemical signals from outside the cell to the cell nucleus. This chemical signaling pathway, known as the RAS / MAPK pathway, is essential for normal development before birth, helping to control the growth, proliferation, differentiation, cell movement and apoptosis.
They have identified at least 48 mutations in the BRAF gene, 9 MAP2K1 gene mutations, 13 mutations in the gene map2k2 and several mutations in the KRAS gene, responsible cardiofaciocutaneous Cutaneous syndrome. Mutations in any of these genes result in an overactive protein, disrupting chemical signaling during development. Altered signaling interferes with the development of many organs and tissues, leading to signs and symptoms of the disease. Some people with signs and symptoms of cardiofaciocutaneous Cutaneous syndrome have identified a mutation in BRAF, MAP2K1, map2k2 or KRAS. In these cases, affected individuals may have Costello syndrome and Noonan syndrome, which are also caused by mutations in genes involved in the RAS / MAPK signaling. The encoded proteins from these genes are part of the same pathway chemical signaling, which helps explain why mutations in different genes may cause alterations with similar signs and symptoms.
Syndrome Cutaneous cardiofaciocutaneous is considered an autosomal dominant disease, which means that a copy of an altered gene in each cell is sufficient to cause the alteration. Other cases are caused by new genetic and occurs in people with no history of disease in your family mutations. In a few cases, an affected person inherits the disease from an affected parent.
Tests in IVAMI: in IVAMI perform the detection of mutations associated with syndrome cardiofaciocutaneous Cutaneous (CFC), by complete PCR amplification of the exons of the BRAF, KRAS, MAP2K1 and map2k2 genes, respectively, 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).