Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Peutz-Jeghers Syndrome (PJS) [Q85.8]

OMIM numbers: 175200, 602216 (STK11)

Dr. rer. nat. Karin Mayer

Scientific Background

The Peutz-Jeghers syndrome (hamartomatous intestinal polyposis) is a rare, autosomal dominant disease and is sporadic in approx. 50% of all cases. The frequency is estimated to be 1:25,000 to 1:280,000. Two symptom complexes are characteristic: I) hamartomatous polyps in the GI tract (predilection of the jejunum for intussusceptions, obturations and intestinal bleedings, secondary anemia), II) melanin spots (melanocytic macules) on the lips, mucous membranes, fingers, toes and vulva. The clinical criteria for a diagnosis were defined in 2010. Patients have a disposition for gastrointestinal tumors and are at an increased risk for ovarian, cervical, pancreatic, pulmonary, testicular and breast cancer. The cumulative risk for carriers of developing an intestinal or extra-intestinal tumor in the course of their lives is up to 90%.

The disease is caused by mutations in the STK11 (LKB1) gene which encodes a serine threonine kinase with tumor suppressor activity. Inactivating mutations lead to faulty regulation of the mTOR pathway, which plays a key role in the origin of hamartomatous syndromes. The detection rate of point mutations in STK11 is approximately 70% in patients with a clinically confirmed diagnosis and positive family history; in sporadic cases it is 20-60%. Since 15-30% of all mutations in STK11 are deletions of single or several exons, the sensitivity of diagnostics can be increased to 90% if several methods are combined (such as DNA sequencing and MLPA (multiplex ligation-dependent probe amplification)).

In predictive genetic testing, at-risk, asymptomatic individuals are tested, usually first-degree relatives of affected patients. According to the Genetic Diagnosis Act (GenDG) genetic counseling should be offered along with any genetic diagnostic procedure. In the case of predictive genetic testing, genetic counseling must be carried out prior to testing as well as after having received the result, unless there exists a written waiver of the at-risk person after having received written information on the content of the counseling. According to the recommendations of medical societies genetic testing should be accompanied by psychotherapeutic counseling prior to, during and after the genetic diagnostic procedure.