Cronkhite-Canada Syndrome

Updated: Jan 14, 2016
  • Author: Kruti Parikh; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

Cronkhite-Canada syndrome (CCS) is a rare, sporadically occurring, noninherited disorder reported for the first time in 1955 by Leonard W. Cronkhite, Jr, and Wilma J. Canada as a new distinct clinical entity in 2 female patients with generalized gastrointestinal polyps, cutaneous pigmentation, alopecia, and onychodystrophy. [1]

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Pathophysiology

The etiology of Cronkhite-Canada syndrome (CCS) is unknown. No evidence exists to suggest a familial predisposition. The possibilities of asymptomatic offspring or afflicted patients have not been excluded. Reports suggest immune dysregulation as the basis of Cronkhite-Canada syndrome. [2, 3, 4, 5] Many patients with Cronkhite-Canada syndrome have positive antinuclear antibodies as well as a variety of autoimmune diseases such as systemic lupus erythematous, rheumatoid arthritis, scleroderma, and hypothyroidism. [6] Cronkhite-Canada syndrome patients have also been found to have elevated serum IgG4 levels. Elevated IgG4 plasma cells are also seen in colonic polyps from patients with CCS. This autoimmune etiology is further supported by excellent clinical response to systemic steroids and azathioprine. [2]

Negoro et al demonstrated that germlike mutations of the tumor suppressor gene PTEN (phosphatase and tensin homologue), located at 10q23.3, which is responsible for another gastrointestinal polyposis syndrome (Cowden disease), is not detected in persons with Cronkhite-Canada syndrome. [7] Senesse et al described Cronkhite-Canada syndrome in association with arsenic poisoning. [8]

Gastrointestinal lesions in Cronkhite-Canada syndrome are hamartomatous polyps generally involving the entire gastrointestinal tract except for the esophagus. [4, 5, 9] Histologically they reveal pseudopolypoid-inflammatory changes. Cutaneous symptoms are believed to be due to malabsorption; however, ectodermal changes did not appear to parallel the disease activity and improved despite gut dysfunction in some reported cases. Multiple brownish macules and patches also preceded the onset of gastrointestinal symptoms in one of the first reported cases of Cronkhite-Canada syndrome.

Infantile Cronkhite-Canada syndrome (similar to typical Cronkhite-Canada syndrome) includes juvenile gastrointestinal polyps, alopecia, nail changes, and macrocephaly. Infantile Cronkhite-Canada syndrome is believed to be a special variant of juvenile gastrointestinal polyposis. Its mode of inheritance is assumed to be autosomal recessive; however, parental consanguinity was not present in either described case. This raises the question of whether infantile Cronkhite-Canada syndrome may be a sporadic condition. [10, 11]

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Epidemiology

Frequency

Cronkhite-Canada syndrome has a worldwide distribution; over 500 cases have been reported. [12] The majority of these cases have been documented in Japan, including a large series of 180 patients. [13] Cronkhite-Canada syndrome is a rare disorder. [13, 14, 15, 16] Based on the large Japanese series, the estimated incidence of Cronkhite-Canada syndrome is about 1 case per million population. [13]

Race

No data are available on racial predisposition. Cronkhite-Canada syndrome has a worldwide distribution; however, most reported cases come from Japan.

Sex

Cronkhite-Canada syndrome does show a slight male predominance, with a male-to-female ratio of 3:2. [9]

Age

The typical onset of Cronkhite-Canada syndrome is during middle or old age. The average age is 59 years; the range is 31-86 years. Some reports suggest that the disease may remain asymptomatic, thus not being diagnosed for a long time. [17, 18]

Most patients are older than 50 years at the time of presentation.

The reported cases of infantile Cronkhite-Canada syndrome are scant (<10). [10]

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