Cronkhite-Canada Syndrome: First Report of Two Familial Cases in China

Background: Cronkhite-Canada syndrome is a rare disease of unknown etiology. Until now, no evidence exists to suggest a familial predispositions. Case Presentation: We present two familial cases: one a 31-years old female patient with chronic watery intermittent diarrhea and abdominal pain for 12 years and hematochezia for one month. She aslo had hyperpigmentation over hands, onchodystrophy, alopica, hypogeusia, anorexia and weight loss (since 6 years). Her 9-years old son also experienced intermittent abdominal pain, diarrhea and hematochezia for 1 year. Gastrointestinal endoscopy showed multiple polyps in stomach and colon in both cases. Suspecting a genetic association, we assessed the sequence variation of the exon region of Polyposis related gene in the mother using next generation sequencing (NGS). A mutation of APC gene c.3921-3925delAAAAG (p.Ile1307fsX6) was found. This mutation site was examined in the patient’s mother, father, three siblings and son by PCR-sanger sequencing. Only the son had a mutation in the same site. The familial case of Cronkhite-Canada syndrome was suspected. Conclusion: So far, there is no strong evidence to suggest a familial predisposition. We report a case of Cronkhite-Canada syndrome in mother and son suggestive of familial predispositions. We have found that they have same mutations in APC gene by genetic testing.

( Figure 1A), hyperpigmentation over hands and onchodystrophy ( Figure 1B). The abdominal examination was unremarkable and had no lymphadenopathy. There was no abnormality seen on CT scan of abdomen and MRI scan for bone and brain. The white blood cells count was 3.50*10^9/L; red blood cells 3.9*10^12/L; hemoglobin 115g/L; lymphocyte 39.9%; mononuclear cell 11.5%; neutrophil 1.6410^9/L↓; hematocrit 0.348L/L ↓; and no abnormal reticulated red cell count was identified. The electrolytes: magnesium 1.27mmol/L; globulins 36.8g/L; apolipoproteins A10.87g/L and the upper endoscopy revealed multiple sporadic small polyps in the stomach (Figure 2A).

Figure 1:
(A) Thirty-one years old female with alopecia over scalp.
(B) Dystrophic changes over toes nails and hyperpigmentation over hands.
Colonoscopy showed numerous sessile polyps scattered through the colon ( Figure 2B). The polyps were ranged in size of 2mm to 3 cm in size. Ileal polyps were also present. Capsule endoscopy showed normal small intestine. She was also accompanied her 9year old son whose was suffering from intermittent abdominal pain, diarrhea
Since then, nearly 550 cases of Cronkhite-Canada syndrome have been reported worldwide. The average age of onset is estimated to be between 50 -60 years with a 3:2 male/female ratio [4,5].
Considering the present scenario, the etiology of the Cronkhite-Canada syndrome remains unclear. However, an autoimmune process is suspected due to increase of IgG4 levels which are found in Cronkhite-Canada syndrome polyps [4][5][6]. Till date, no evidence exists to suggest a familial predisposition. The possibilities of symptomatic offspring or afflicted patients were not excluded.
Here, we got a case of Cronkhite-Canada syndrome in a 31-year-old mother and 9-years old son suggestive of familial predispositions.
We have found that they have same mutations in APC gene by genetic testing. The optimal treatment of Cronkhite-Canada syndrome is currently unknown due its rarity and unclear etiology.
Nutritional support aimed for improving electrolytes and mineral deficiencies that can rarely induce complete remission as observed in our patients. In fact, current studies favor a combination therapy based on nutritional support and corticosteroids. Unfortunately, due to rarity of this disease, optimal screening protocol has also not been developed, although annual endoscopic surveillance has been widely practiced.
Despite therapy, mortality rate approaches 65%. However, there are long term survivors and some individuals who undergo spontaneous remission. There is no effective therapy for this condition, despite the use of systemic anabolic steroids has been reported. Resection of stomach and colorectum maybe indicated if heavily carpeted with polyps or source of excessive bleeding, bowel obstruction or cancer. In conclusion, based on genetic testing we concluded that, mother may have developed CCS from FAP, there is a possibility that the son may also develop CCS later because we found the mutation in the sane gene. The average age of CCS is 30-80 years. The symptoms in the son are not obvious as he is too young. Our results have significance scope for developing an optimal screening and treatment for the patients who are suffering from Cronkhite-Canada syndrome.