Nevoid Basal Cell Carcinoma, Síndome Gorlin (Gorlin syndrome, Nevoid basal cell carcinoma syndrome) - Gen PTCH1.
Naevoid Basal Cell Carcinoma, also known as Gorlin syndrome, is a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors.
In people with Gorlin syndrome, cancer type most frequently diagnosed is basal cell carcinoma. In general, these individuals begin to develop basal cell carcinomas during adolescence or early adulthood. These cancers occur most often on the face, chest and back. The number of basal cell carcinomas that develop during the life of a person varies among affected individuals. Some people never develop basal cell carcinoma, while others may develop thousands of these cancers. People with lighter skin are more likely to develop cancers that people with darker skin basal cells. Most of those affected also develop non - cancerous tumors of the jaw, odontogenic tumors called keratocystic. These tumors usually occur first during adolescence and develop until about 30 years old. If untreated, these tumors can cause facial swelling and painful displacement of teeth.
People with Gorlin syndrome have an increased risk of other tumors such as medulloblastoma, childhood. In addition, fibroids may develop in the heart or a woman's ovaries. Overall, heart fibroids cause no symptoms, but they can block blood flow or cause arrhythmia. Ovarian fibroids do not affect fertility. Additional features of Gorlin syndrome include small depressions in the skin of the palms and soles of the feet, macrocephaly with a prominent forehead and skeletal abnormalities involving the spine, ribs or skull. These signs and symptoms are usually evident at birth or early childhood.
This process is due to mutations in the PTCH1 gene, located on the long arm of chromosome 9 (9q22.3). The PTCH1 gene is a tumor suppressor gene. This gene encodes a protein called patched-1 which functions as a receptor. A protein called Sonic Hedgehog is the ligand for this protein. Ligands and their receptors trigger signals that affect cell development and function. Specifically, this pathway plays a role in cell growth, cell specialization and determining how many different parts of the developing organism. When Sonic Hedgehog is not present, patched-1 blocks cells grow and proliferate. When bound to Sonic Hedgehog, patched-1 stops suppressing cell proliferation.
They have identified more than 225 mutations in the PTCH 1 gene in people with Gorlin syndrome. Mutations in this gene prevents encoding patched-1 or encoding result of an abnormal version of the receptor. A patched-1 receptor altered or absent can not effectively suppress the growth and cell division. As a result, the cells proliferate uncontrollably resulting tumors characteristic of Gorlin syndrome. It is less clear how mutations in the PTCH 1 gene cause other signs and symptoms related to laenfermedad.
The characteristic features of Syndrome Gorlin may also be associated with a chromosomal microdeletion change called 9q22.3, in which a small portion of chromosome 9 is removed in each cell. This deletion includes the segment of chromosome 9 containing the PTCH1 gene. Therefore, people with a 9q22.3 microdeletion not have a copy of this gene. The loss of this gene underlying signs and symptoms of Gorlin syndrome in people with microdeletions 9q22.3. Affected individuals also have features that generally are not associated with Gorlin syndrome, including developmental delay, mental retardation, macrosomia and other physical abnormalities. It is believed that these other signs and symptoms may be due to the loss of additional genes in the deleted region of chromosome 9.
Gorlin syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for alteration is expressed. In most cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the PTCH 1 gene and occur in people with no history of disease in your family. Having a mutated copy of the PTCH1 gene in each cell is sufficient to result in the characteristics of Gorlin syndrome, including macrocephaly and skeletal abnormalities. For basal cell carcinomas and other tumors that develop, a mutation in the second gene copy PTCH1 it should also occur in certain cells during the life of the person. Most people born with a genetic mutation PTCH1 eventually acquire a second mutation in some cells and therefore various types of tumors develop.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Gorlin syndrome, by complete PCR amplification of the exons of the PTCH1 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).