Peutz-Jegher’s Syndrome
Peutz-Jegher’s Syndrome (PJS) is a rare autosomal dominant disorder. Thus, it is not a sex-related disorder and can instead be inherited from either parent. PJS affects an estimated 1 in 25,000 people. It is caused by mutations in the STK11 gene located on chromosome 19. If a parent has PJS, there is a 50% chance that the child will inherit the disorder as well. The most common symptoms of PJS are unusually located freckles, such as on the lips or around the anus, and gastrointestinal polyps. Therefore, PJS is usually initially diagnosed from the presence of those two symptoms and confirmed by family medical history or genetic testing. Gastrointestinal polyps, or hamartomas, usually occur in the small intestine, where they cause abdominal pain and bowel blockage. Hamartomas can also be found in the colon (large intestine) and stomach, though less often. Hamartomas tend to be the most problematic symptom; many PJS patients require surgery to remove obstructions in the intestines. Patients with PJS need regular intestinal examinations, such as endoscopy, colonoscopy, and x-rays, to monitor the hamartomas (Cleveland Clinic 2003).
PJS is also associated with up to a 93% chance of developing breast, ovarian, stomach, esophageal, colon, and pancreatic cancers. STK11 is a tumor suppressor gene that controls cell growth and death. Both copies of STK11 must be mutated for a person to develop cancer. Normally, a person will inherit a mutated copy form one parent, so it is present in all of the body’s cells. This is called a germline mutation. Sometimes a person will only have the germline mutation and will therefore never develop cancer. However, sometimes a second mutation occurs. The location of the second mutation determines the type of cancer that can possibly develop. For example, if the second mutation happens in a breast cell, then that person may get breast cancer. Tumors will not develop, though, unless there are several mutations in several growth control genes. It is not known for certain what causes the mutations to occur. Some may just be random, but others may be caused by environmental factors or carcinogens (Tiainen, Ylikorkala & Makela 1999).
STK11 encodes a 60-kDa serine/threonine kinase. The function of the kinase is not yet known. Mutations in STK11 result in greatly reduced mRNA expression. Normally, STK11 suppresses growth by causing G1 cell cycle arrest. However, the exact mechanisms of how it does just that are not presently known either (Tiainen, Ylikorkala & Makela 1999).
Peutz-Jegher’s Syndrome. Cleveland Clinic. [World Wide Web site]. [accessed 28 Dec 2007]. URL: http://www.clevelandclinic.org/registries/inherited/pjs.htm.
Tiainen, M.; Ylikorkala, A.; and T.P. Makela. 1999. Growth Suppression by Lkb1 is Mediated by a G1 Cell Cycle Arrest. Proceedings of the National Academy of Sciences of the United States of America, Vol. 96(16). p. 9248-9251. Accessed through JSTOR.
http://links.jstor.org/sici?sici=0027-424%2819990803%2996%3A16%3C9248%3AGSBLIM%3E2.0.CO%3B2-S
