Peutz-Jeghers syndrome ..., (intestinal polyposis skin pigmentation-syndrome ..., perioral lentigines; Lentiginosis periorificial; Intestinal Polyposis II) (Peutz-Jeghers syndrome) - Gen STK11.

The Peutz-Jeghers syndrome is basically characterized by the presence since childhood hamartomatous intestinal polyps, mucocutaneous pigmentation and a significant increased risk of developing certain cancers. Affected individuals have brown or black spots on the oral mucosa and perioral as well as on the face, forearms, palms, soles, fingers and perianal area. These manifestations occur during the first years of life and tend to progress with age, except those of the perioral area. Gastrointestinal polyps can be distributed throughout the gastrointestinal tract, but are somewhat more common in the small intestine. Also usually they begin in childhood, during the first decade of life, and symptoms occur when polyps grow in number and size and have heart attacks, ulcers or recurrent intestinal obstructions during the second or third decade of life.

Furthermore, individuals affected by the Peutz-Jeghers syndrome have a high predisposition for developing both gastrointestinal malignancies extraintestinal. In fact, a meta-analysis showed that the risk of an individual with Peutz-Jeghers syndrome to develop cancer before age 64 was 93%. Cancers of the gastrointestinal tract occurring in the colon (40%), stomach (30-60%), esophageal (5-33%), small intestine (15-30%) and pancreas (35%). The most common intestinal tumors are breast (31%), the ovary (18%) and lung (13%), but also have increased risk those located in the neck, thyroid and prostate.

Genetic alterations associated with the development of this syndrome and thus to cancers derived from it, have been located in STK11, also called LKB1, located on the short arm of chromosome 19 (19p13.3). This gene encodes a serine / threonine tumor suppressor phosphorylating and activating acting related kinases AMPK subfamily members kinase. STK11 / LKB1 plays an essential role in cell cycle arrest at the G1 phase in cell polarity and in p53 - dependent apoptosis. Therefore, when the protein is truncated due to mutations in the sequence coding for the risk of tumor development increases exponentially. In addition to its role as a tumor suppressor function of serine / threonine kinase 11 it appears to be necessary for normal development before birth.

They have been identified in STK11 in people with Peutz-Jeghers, 83 missense mutations, 29 mutations splicing (splicing), 114 deletions, insertions 43, 10 insertions / deletions and rearrangements 4 complex syndrome. Many of these mutations result encoding an abnormally short version, no functional serine / threonine kinase enzyme 11. Other mutations change the amino acids used for the formation of the enzyme. Mutations in STK11 alter the tumor suppressor function of the enzyme, allowing the cells to grow and divide without control or order. This uncontrolled growth of cells can lead to the formation of hamartoma polyps and cancers.

The Peutz-Jeghers syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to increase the risk of developing cancerous polyps and cancers. In about half of all cases, an affected person inherits a mutation in the STK11 gene from one affected parent. The remaining cases occur in people with no history of disease in your family. These cases appear to be due to new mutations in the STK11 gene.

Tests in IVAMI: in IVAMI perform detection of mutations associated with the Peutz-Jeghers syndrome, by complete PCR amplification of the exons of STK11, and subsequent sequencing. For detecting insertions, duplications and deletions perform quantification by real time PCR [Real time qPCR].

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).