The diagnosis of Peutz-Jeghers syndrome relies primarily on the presence of certain symptoms, including hamartomatous (benign, non-cancerous) intestinal polyps, altered pigmentation of the skin and mucus membranes, and/or a family history of PJS.

The symptoms of Peutz-Jeghers syndrome can vary within a family. Some affected individuals may have only polyps or altered pigmentation, while others may develop more extensive symptoms. Since people with PJS often show subtle symptoms, it is possible this condition is under-diagnosed in families and that more individuals with Peutz-Jeghers syndrome have inherited the condition from their parents than currently thought.

Intestinal polyps
The polyps seen in individuals with Peutz-Jeghers syndrome are most often found in the small intestine, but they can also occur in the stomach and large bowel. During childhood, polyps are typically non-cancerous, but they can bleed and cause anemia (lowering the level of healthy red blood cells) and block the intestines. The age at which polyps are first observed in individuals with PJS can vary among families. One study showed that children most often showed their first gastrointestinal symptoms at age 10 years, and children most often had their first polyps removal (polypectomy) at age 13 (Amos et al., 2004).

Mucocutaneous pigmentation
Mucocutaneous pigmentation (altered coloring of the skin, gums and other mucus membranes) is rarely present at birth, but develops during early childhood (usually before age 5) as dark blue to dark brown flat spots around the mouth, eyes and nostrils; in the peri-anal area; on the gums; and on the fingers. The spots can fade in puberty and adulthood. One report estimates 82 percent of patients with Peutz-Jeghers syndrome have freckling (Amos et al., 2004). That means approximately 18 percent of patients do not have freckling but remain at risk to develop other features of PJS.

Family history
A careful and detailed review of a person's medical and family history is important in diagnosing Peutz-Jeghers syndrome. A doctor or genetic counselor may construct a pedigree, or a multi-generation family tree, that shows which members of the family have developed cancer, the types of cancer and the ages of onset, as well as the presence of any symptoms. If the pattern of symptoms and/or cancers is suggestive of Peutz-Jeghers syndrome, the physician or counselor may recommend genetic testing be performed.

Testing for Peutz-Jeghers syndrome (PJS)
Genetic testing can confirm on a molecular level whether an individual has Peutz-Jeghers syndrome:

First, a blood or saliva sample is obtained.

DNA is isolated from the sample and the two copies of the STK11 gene are evaluated using a variety of methods and compared to the normal reference sequence for STK11.

If an alteration in one STK11 gene copy is identified, the genetic counselor can next examine whether the alteration has been previously reported in other individuals with Peutz-Jeghers syndrome.

This information could further strengthen the conclusion that the STK11 alteration was the cause of the symptoms in the individual.

In individuals with a clinical diagnosis of PJS, molecular genetic testing of the STK11 gene reveals disease-causing alterations in approximately 100 percent of individuals who have a positive family history. Approximately 90 percent of individuals who have a clinical diagnosis but no family history of Peutz-Jeghers syndrome are found to have an alteration in STK11. However, not all patients with Peutz-Jeghers syndrome carry a detectable alteration in the STK11 gene. Therefore, the failure to identify an alteration in the STK11 gene does not exclude a diagnosis of PJS.