Cronkhite-Canada Syndrome

sorption and a profound malnutrition. Like all the hereditary polyposis syndromes, subjects with CCS are also prone to develop cancer. Among all patients with CCS 50 (13%) cases were associated with gastrointestinal cancer, including 31 (8%) cases with colon cancer (usually in the rectosigmoid area) and 19 cases (5%) with gastric cancer [7] . Of particular interest is that males were signifi cantly more prone to cancer genesis than females (27 out of 31). JPS presents during the fi rst or second decades in life, and feature a similar phenotype like CCS. In both syndromes the presented symptoms are very much alike: diarrhea, bleeding and malnutrition. Polyps develop throughout the entire GI tract and there is an increased risk for GI malignancies. Cancers appear to arise from adenomatous components present in some juvenile polyps [8] . JPS is inherited as a rare autosomal-dominant disease, yet signifi cant numbers of cases are sporadic with no previous familial history. PJS is another similar syndrome. It is an autosomaldominant disorder characterized by the presence of numerous hamartomatous polyps throughout the entire GI tract (mostly in the small bowel) along with mucocutaneous melanin pigmentation spots that appear most commonly on the lips and buccal mucosa. Many organs are prone to cancer in these patients, and the small bowel in particular. Is it possible that JPS and/or PJS are a form of CCS or vice versa? Both JPS and PJS are examples of syndromes with a genetic predisposition that may vary from ‘high’ to ‘low’ penetrance, and between ‘familial’ and ‘sporadic’ cases [4] . The genes that are associated with predisposition to these syndromes have been recently identifi ed. Cronkhite-Canada syndrome (CCS) is a rare sporadically occurring non-familial syndrome. It was fi rst reported in 1955 by Leonard Wolsey Cronkhite Jr., an American internist and Wilma Jeanne Canada, an American radiologist, as a new distinct clinical entity diagnosed in 2 women [1] . Since then, several case reports and few small series have been published. Large studies evaluating pathogenesis and medical treatment do not exist because of the rareness of this syndrome. The distribution of the disease varies signifi cantly around the world, while about 75% of the cases are diagnosed in Japan [2] . The etiology, pathogenesis, clinical course, prognosis and optimal treatment are yet to be determined. There is no evidence to suggest a genetic, environmental or specifi c infectious origin or a reason for its being largely confi ned to Japan. Comparing this syndrome to other similar genetic gastrointestinal polyposis syndromes that are associated with dermatologic symptoms and malabsorption is of a special interest. There is signifi cant phenotypic overlap between the features of CCS, jeuvenile polyposis (JPS) and Peutz-Jegher syndrome (PJS), and in particular in the morphology of intestinal hamartomatous polyps [3, 4] . CCS usually manifests in the sixth decade. It is characterized by the presence of non-adenomatous juvenile type or hamartomatous polyps that occur throughout the gastrointestinal (GI) tract excluding the esophagus [5] . The polyps are a part of a generalized GI mucosal disturbance that results in malabsorption and protein losing enteropathy. The vast majority of affected individuals manifest with alopecia, skin pigmentation and alterations in the nail beds. These ectodermal features and the various clinical courses [6] are probably a consequence of malabPublished online: May 31, 2005