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Keywords: Gastrointestinal system; Clinical cytogenetics

Authors:
M. Ibrahim 1; A. Ibrahim 2; M.J. Hajianpour 3

Affiliations:
1) Internal Medicine, East Tennessee State University, Johnson City, Tennessee.; 2) School of Medicine, University of Jordan, Amman, Jordan; 3) Division of Medical Genetics, Department of Pediatrics, East Tennessee State University


Peutz-Jegher syndrome (PJS) is a rare autosomal dominant syndrome usually due to a germline mutation in STK11 gene. It is characterized by multiple hamartomatous polyps in the gastrointestinal tract with mucocutaneous pigmentation and has an increased risk of cancer.Currently only mutations in STK11 (AKA LKB1) have been identified as causative of PJS. The STK11 gene sequencing detects 55% of cases when the family history is positive for PJS, and 70% of sporadic cases. Deletion/duplication analysis detects 45% of familial cases and 21% of sporadic cases. High penetrance rate by the age of 30 years, but 10-20% of the cases result from de novo mutations¹. To our knowledge this is the first report of association of APC gene alteration and Peutz-Jegher syndrome (PJS).
A 56-year-old who presented to the emergency department with abdominal pain and rectal bleeding.No family history of PJS, but breast and colon cancer found in first degree relatives.He had dysphagia, nausea, vomiting and fatigue at presentation with pallor, multiple nevi/brown spots over the arms and legs and right palm, superficial tenderness in the right side of the abdomen on physical examination. Rectal examination revealed no masses or active bleeding at the time.Patient has renal cyst, iron- deficiency anemia and a history of recurrent rectal bleeding over the past four years.Upper GI endoscopy showed duodenal hamartomatous polyps; histologically P-J polyps with a stricture at the distal esophagus.
Colonoscopies performed over the past 8-10 years showed 2-10 polyps which were histologically confirmed to be benign tumors with atypical hyperplasia. Molecular studies showed a variant of uncertain significance (VUS) of APC gene: c2297C>T (p. Ala766Val) (aka A766V (2297C>T). The APC gene is associated with familial adenomatous polyposis (FAP). The sequencing and deletion/ duplication analysis of STK11 gene was normal.
A clinical diagnosis with PJS requires the presence of any one of the following:
Two or more histologically confirmed Peutz-Jeghers (PJ) polyps, any number of PJ polyps detected in an individual who has a family history of PJS in a close relative, characteristic mucocutaneous pigmentation in an individual who has a family history of PJS in a close relative, any number of PJ polyps in an individual who also has characteristic mucocutaneous pigmentation.