Peutz-Jeghers Syndrome: STK11 Gene Deletion/Duplication

Condition Description

Peutz-Jeghers syndrome (PJS) is anautosomal dominant condition characterized by the association ofgastrointestinal polyposis and mucocutaneous pigmentation. Peutz-Jeghers-typehamartomatous polyps are most common in the small intestine (in order ofprevalence: in the jejenum, ileum, and duodenum) but can also occur in thestomach and large bowel. Gastrointestinal polyps can result in chronic bleedingand anemia and cause recurrent obstruction and intussusception requiringrepeated laparotomies and bowel resections. Variableexpressivity is common; some affected individuals in families with PJS may have only polyps or perioral pigmentation.

The age at onset for symptoms frompolyps is variable, with some individuals developing symptoms within the firstfew years of life. Significant interfamilialvariability is observed in the age at which polyps are firstobserved, suggesting that the natural history of polyps in a family may be apredictor of severity for offspring. In studies from MD Anderson Cancer Center,the median age at first GI symptoms was ten years, while the median age atfirst polypectomy was age 13 years. A report from Korea indicated a mean age of onsetfor GI symptoms of 12.5 years. In a review of 32 kindreds with PJS, laparotomyfor bowel obstruction was performed in 30% of individuals by age ten years andin 68% by age 18 years.

Mucocutaneous hyperpigmentationpresents in childhood as dark blue to dark brown macules around the mouth,eyes, and nostrils, in the perianal area, and on the buccal mucosa.Hyperpigmented macules on the fingers are common. The macules may fade inpuberty and adulthood. Individuals with Peutz-Jeghers syndrome are at increasedrisk for malignancies (colorectal, gastric, pancreatic, breast, and ovariancancers). Females are at risk for sex cord tumors with annular tubules (SCTAT),a benign neoplasm of the ovaries, and adenoma malignum of the cervix, a rareaggressive cancer. Males occasionally develop calcifying Sertoli cell tumors ofthe testes, which secrete estrogen and can lead to gynecomastia.

The diagnosis of Peutz-Jegherssyndrome is based on clinical findings. In individuals with a clinicaldiagnosis of PJS, molecular genetictesting of the STK11(LKB1) gene(19p13.3) reveals disease-causing mutations in approximately 100% ofindividuals who have a positive family history and approximately 90% of individuals who have no family history of PJS.

About 50% of probands have an affected parent and about 50% have no family history of PJS, but the proportion of cases caused by de novo gene mutations is unknown as the frequency of subtle signs of the disorder inparents has not been thoroughly evaluated and molecular genetic data areinsufficient. Parents of affected individuals with no known family history of PJS should be evaluated clinically, and with molecular genetictesting if a disease-causing STK11 mutation has been identified in the proband.The risk to the offspring of a proband with a positive family history is 50%. The risk to offspring of a proband with a negative family history is 50% if the proband tests positive for a pathogenic STK11 mutation.The risk to offspring of a proband with no family history of PJS who tests negative for an STK11 mutation remains unknown.

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Genes (1)


This test is indicated for:

  • Confirmation of a clinical diagnosis of PJS in individuals who have tested negative for sequence analysis
  • Individuals at-risk for PJS due to family history who have tested negative for sequence analysis


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (
Submit only 1 of the following specimen types
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Sequencing analysis of the STK11 gene is available (VL) and is required before deletion/duplication analysis.
  • Prenataltesting is available to individuals who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.

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