Peutz-Jeghers syndrome

Abstract

Purpose of review Peutz-Jeghers syndrome is a rare, autosomal dominant, hereditary polyposis syndrome defined by gastrointestinal hamartomas and mucocutaneous pigmentations, caused by a germline mutation in the serine/ threonine kinase 11 or liver kinase B1 (STK11/LKB1) genes. Hamartomatous polyps located throughout the gastrointestinal tract can be complicated by bleeding and small bowel intussusception, potentially leading to the need for emergency surgery. Individuals suffering from Peutz-Jeghers syndrome have an increased lifetime risk of various forms of cancer (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular). Surveillance should lead to the prevention of complications and thus a reduction in mortality and morbidity of patients. Recent findings A combined approach based on wireless capsule endoscopy, magnetic resonance enterography and device-assisted enteroscopy is effective in reduction of the polyp burden and thus decreasing the risk of bleeding and intussusception. Current guidelines for screening and surveillance are mostly based on expert opinion rather than evidence. Summary Peutz-Jeghers syndrome is an emerging disease that significantly affects the quality of life enjoyed by patients. Despite of all the progress in improved early diagnostics, options for advanced endoscopic therapy and elaborate surveillance, acute and chronic complications decrease the life expectancy of patients suffering from Peutz-Jeghers syndrome.

Determinants of Homologous Recombination Deficiency in Pancreatic Cancer

“…The association between STK11 mutations, of which germline variants drive Peutz-Jeghers syndrome, and PARPi sensitivity remains relatively unexplored [ 65 ]. STK11 codes for LKB1, a serine-threonine kinase, which plays a role in DNA damage repair [ 66 ].…”

Genotypic and Phenotypic Characteristics of Hereditary Colorectal Cancer

“…PJS is a hereditary syndrome manifesting in early childhood and characterized by gastrointestinal hamartomatous polyposis, mucocutaneous pigmented macules, and predisposition to various cancers [ 49 ]. Patients with PJS are at an increased risk of gastrointestinal cancers including of the colon, small bowel, biliary tract, pancreas, stomach, and esophagus, in addition to a wide variety of extraintestinal malignancies, including breast, uterine, cervical, lung, ovarian, and testicular cancers [ 49 ]. The overall risks of developing any cancer at ages of < 30, 40, 50, 60, and 70 years are 1% to 3%, 19%, 32%, 63%, and 81%, respectively.…”

“…A pathognomonic feature of intestinal hamartoma is the proliferation of smooth muscle cells derived from the underlying muscularis mucosae, growing in an arborizing pattern to displace the surface epithelium into the submucosa and muscularis propria, and featuring pseudoinvasion [ 50 ]. Mucocutaneous presentation includes pigmented dark blue, brown, to black macules distributed on the lips, perioral areas, buccal mucosa, eyes, nostrils, fingertips, palms, soles, and perianal areas, without malignant transformation [ 49 ]. The PJS phenotype manifests when germline serine/threonine protein kinase ( LKB1 ) mutations are accompanied by an acquired defect/second hit in the other allele in somatic cells, and is transmitted by autosomal dominant inheritance [ 51 ].…”

Family with Peutz–Jeghers syndrome in Indonesia

“…There is also a high risk of malignancy, particularly gastrointestinal cancer. The disease is caused by mutations in a tumor suppressor gene, STK11 or LKB1 , that is located on chromosome 19p13.3 1–4 …”