The Uruguayan Registry for Peutz-Jeghers Syndrome: Clinical and Genetic Results and Report of a Novel Mutation

Abstract

Purpose: Peutz-Jeghers syndrome (PJS) is a hereditary disorder characterized by intestinal polyps, mucocutaneous pigmentation and increased risk for cancer. It is caused by mutations of the serine threonine kinase 11 (STK11) gene. Uruguay is a South American country with 3 million inhabitants. The aim of this study was to collect and analyze epidemiological, clinical and genetic data from all patients with PJS in Uruguay. Methods: Data were analyzed until May 2009 for the purpose of this study. Data was obtained from public and private medical centers or submitted by treating physicians. Patients were contacted personally or through their treating clinicians. Clinical data were input into a digital chart and updated annually. Sequencing of the STK11 gene in one member of each available family was performed to look for the presence of gene mutation. Results: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age at time of diagnosis was 18.28 years (range 2-65). Currently, there are 17 individuals with PJS alive. In 16, annual follow up has been completed. Average age for all-causes of death was 41 years, being cancer the most frequent cause. All patients had characteristic PJS pigmentation. All affected patients who had evaluation of the gastrointestinal tract had polyps (n=22). Polyps were most frequent in the small bowel and colon. Eighteen cases (72%) required urgent surgery due to intestinal obstruction secondary to the presence of polyps. Eleven cases (44%) had anemia. Five cases (20%) in 3 families had a seizure disorder. Seven patients (28%) developed cancer and two patients had more than one cancer, with breast being the most frequent site. A mutation in the STK11 gene was found in 8 of the 9 families analyzed. Deletion of all or part of the STK11 gene was identified in 5 patients from 5 families. Other mutations seen included c.666delC (1 family), IVS2+1 A>G (1 familiy), and M136K (1 familiy). No partial/whole gene deletion or other mutation was identified in 4 patients. To our knowledge, the M136K missense mutation in the STK11 gene has not been reported previously in the literature. Conclusion: The analysis of the Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery by intestinal obstruction, high prevalence of epilepsy, high risk of cancer and shortened life expectancy. A mutation in the STK11 gene was present in the 89% of families analyzed, and a novel, and previously undescribed mutation, was detected in one. Disclosure: Dr Tchekmedyian - no disclosures, Dr Thomas McGarrity - no disclosures, Sherri Bale-employee:GeneDx. This company provides genetic testing in Peutz - Jeghers Syndrome. Christopher I. Amos - no disclosures, Dr Joaquin Berrueta - no disclosures, Dr Natalie Nabon - no disclosures, Dr Henry Cohen - no disclosures.