Gardner's syndrome
What is it?
Gardner’s syndrome is a variant of Familial Adenomatous Polyposis (FAP) with autosomal dominant transmission, associated with the presence of a germline pathogenic variant (mutation) in the APC gene. In addition to the intestinal manifestations typical of FAP (intestinal polyposis, with increased risk of colorectal neoplasia, duodenal polyposis, ampulla of Vater, and gastric hepatoblastoma, and others), Gardner’s syndrome is characterized by extra-intestinal manifestations that are unique compared to classic FAP.
Which are the symptoms?
Extra-intestinal manifestations of Gardner’s syndrome are osteomas of the skull and jaw, dental anomalies, epidermoid and desmoid cysts, and congenital hypertrophy of the retinal pigment epithelium. Desmoids are soft tissue neoplasms that occur in 12-18% of patients with Gardner’s syndrome. They develop in the abdominal area (abdominal wall and/or intra-abdominally), but also in the chest, upper and lower limbs. They sometimes show locally invasive behavior and a high recurrence rate, but no metastatic potential.
How is it diagnosed?
Gardner syndrome is caused by a pathogenic variant (mutation) in the APC gene. Pathogenic variants in the APC gene are identified by gene sequencing, which is a molecular biology technique that identifies pathogenic variants using two methods (Next Generation Sequencing and Multiplex ligation-dependent probe amplification). In particular, some specific regions of the APC gene, when mutated, predispose to the onset of the tumors characteristic of Gardner’s syndrome. In particular, the regions between the nitrogen bases number 1395 and 2000 are those that particularly increase the risk of developing desmoid tumors and others characteristic of Gardner’s syndrome. APC gene, when mutated, causes rapid and uncontrolled cell multiplication. This leads to the formation of the very numerous intestinal polyps, each with malignant potential.
How is it treated?
As in classic FAP, preventive strategies are aimed at early identification of preneoplastic lesions. Prompt treatment of the latter will prevent the development of advanced neoplasia. Prevention consists, therefore, in the regular surveillance of the body districts at risk of developing neoplasia, in particular the gastrointestinal tract (colorectum, stomach, duodenum and papilla of Vater, small intestine), and thyroid. Surveillance of other districts is evaluated on a case-by-case basis depending on the clinical picture and/or familiarity for neoplasia in that district. In addition, with regard to the colorectal district, when adenomas become difficult to manage endoscopically due to number/size/characteristics, preventive colectomy surgery is recommended. Beyond what is discussed in FAP syndrome, treatment of desmoid tumors requires a multidisciplinary approach due to their complexity. Locally invasive behavior and variable course with high recurrence of desmoids, requires instrumental surveillance in asymptomatic patients. Complete surgical resection is the treatment option of first choice. In the event of non-resectable tumor or when surgical resection with free margins (R0) is not possible, nonsurgical treatments include radiation therapy and/or chemotherapy.
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