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Peutz-Jeghers Syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased risk of developing multi-organ cancer, mainly in the gastrointestinal tract. Germline mutations of the STK11 gene are usually responsible for this syndrome. The aim of the present work is to report the case of a Uruguayan young patient with an atypical presentation of PJS. Extensive clinical data from the patient was obtained. Characteristic clinical diagnosis based on the presence of mucocutaneous pigmentation of the lips and oral mucosa and gastrointestinal hamartomatous polyps appeared several years later of the first gastrointestinal event (classified as “juveline polyp”) which deferred the molecular diagnosis. Complete sequencing of the STK11 gene was performed by NGS in the proband and his parents. The patient presented a novel large deletion spanning exon 5 to 10 of STK11 gene. This mutation was absent in both parents.

Familial adenomatous polyposis (FAP) is an autosomal dominant genetic condition, caused by mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. Desmoid tumors (DTs) are seen in 15% to 20% of FAP patients. Specific location of mutation serves as a guide to predict colonic and extra colonic manifestations and their aggressiveness. A severe FAP-phenotypic family was registered in a genetic counselling high-risk Uruguayan hereditary cancer clinic. Proband's DNA was analysed by NGS, detecting a pathogenic mutation in APC gene. All willing family members were counselled and encouraged to be tested. Here we report a kindred formed by 16 individuals with a very severe FAP phenotype. A two-base deletion mutation: c.4393_4394delAG in APC gene and a consequent premature stop codon was detected. DTs were diagnosed in 6 individuals, ranging from 2 to 25 years of age. The causes of death were diverse: gastric cancer, rectal cancer and desmoid tumor. The already described genotype-phenotype correlation has proved its worth in this family, as clinical features reflect the mutation location at 3' end of APC gene. The inheritable and lethal nature of the disease needs a tailored follow up approach in order to reduce mortality, optimize local tumor control, and preserve patients' quality of life.