What Is Peutz-Jeghers Syndrome, and Where Does Its Name Come From?

Peutz-Jeghers syndrome is a rare inherited syndrome characterized by polyps in the gastrointestinal tract and mucocutaneous pigmented lesions. It is also a factor that increases the development of cancer.

Patients with Peutz-Jeghers syndrome have an increased risk particularly of gastrointestinal, gynecological (female-specific), breast, liver, and urogenital (urinary-reproductive tract) cancers.

The estimated lifetime risk of any cancer in patients with this syndrome is as high as 93%.

Research suggests that 50% to 80% of families with Peutz-Jeghers syndrome have inherited mutations in the STK11 gene. The remaining cases of Peutz-Jegher syndrome are most likely caused by de-novo mutations (arising spontaneously during life).

Where Does the Name Peutz-Jeghers Syndrome Come From?

Peutz-Jeghers syndrome is named after Dr. Johannes Peutz and Dr. Harold Jeghers.

Born in Uithuizen, the Netherlands, in 1886, Dr. Peutz studied medicine at the Universities of Groningen and Utrecht and graduated in 1914. Dr. Peutz died in 1957.

Born in New Jersey in 1904, Dr. Jeghers completed his undergraduate studies in Biology at Rensselaer Polytechnic Institute in 1928, then continued his education at Case Western Reserve University School of Medicine. Dr. Jeghers subsequently trained in Internal Medicine at Boston City Hospital and died in 1990.  

Neither Dr. Peutz nor Dr. Jeghers was the first to document the syndrome bearing their names. Peutz-Jeghers syndrome was first documented in 1895 by Dr. JT Conner. Dr. Conner described identical twins with oral and labial (mouth and lip) pigmentation (discoloration). One sibling died at age 20 from intestinal obstruction. The other died at age 59 from breast cancer. Dr. Conner did not mention intestinal polyps in his report on these twins.

Based on studies of 7 family members across 3 generations, Dr. Peutz described the connection between intestinal polyps and mucocutaneous lesions in 1921. Following publication of studies on this family, the syndrome became known as “Peutz Disease” in the Netherlands and the rest of Europe. 

In 1939, Dr. Jeghers treated a young girl with melanin pigmentation of the oral mucosa, lips, and fingers, as well as intestinal polyps and bowel obstruction caused by intussusception. When Dr. Jeghers saw a second patient with the same clinical findings, he suspected a distinct syndrome with a genetic explanation. In 1949, Dr. Jeghers described the inherited autosomal dominant pattern for Peutz-Jeghers syndrome. His article cited Dr. Peutz’s 1921 report.

However, the term “Peutz-Jeghers syndrome” was not used until 1954. Dr. Andre Bruwer was the first to use it in an article about this syndrome.

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Peutz-Jeghers Syndrome Today

Epidemiology and Genetics – Peutz-Jeghers syndrome (PJS) is an autosomal dominant syndrome characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and an increased risk of gastrointestinal and extraintestinal cancers.

PJS is associated with germline (inherited) mutations in the STK11 gene, which encodes a serine threonine kinase mapped to chromosome 19p13.3. PJS is rare, with prevalence estimates ranging from 1:8000 to 1:200,000 births.

Symptoms – PJS has two main clinical manifestations: pigmented mucocutaneous macules and multiple gastrointestinal polyps.

• The characteristic mucocutaneous pigmentations (melanin spots) of PJS are present in more than 95 percent of patients and are most commonly seen on the lips and perioral area, palms, buccal mucosa, and soles.
• Gastrointestinal hamartomatous polyps are present in most patients with PJS and can occur anywhere in the gastrointestinal tract. Polyps develop in the first decade of life, and most patients become symptomatic between ages 10 and 30. The number of polyps ranges from 1 to more than 20 per intestinal segment.

Cancer Risk – PJS is associated with an increased risk of gastrointestinal and extraintestinal cancers. Lifetime cancer risk ranges from 37 to 93 percent, and the average age at cancer diagnosis is 42. The most common sites of gastrointestinal malignancy are the colon and pancreas, and the most common extraintestinal cancer site is the breast. Women also have a high risk of cervical tumors, including cervical adenoma malignum and benign ovarian tumors known as “sex cord” tumors with annular tubules (SCTAT tumors). Men with PJS have an increased lifetime risk of Sertoli cell testicular tumors.

Diagnosis – A clinical diagnosis of PJS can be made in the presence of any of the following:

• Two or more Peutz-Jeghers-type hamartomatous polyps in the gastrointestinal tract
• Characteristic mucocutaneous hyperpigmentation of the mouth, lips, nose, eyes, genitals, or fingers in a person with a family history of PJS
• Any number of Peutz-Jeghers polyps in an individual with a family history of PJS in a first-degree relative
• Any number of Peutz-Jeghers polyps in a person with the characteristic mucocutaneous pigmentation of PJS

Individuals meeting the clinical criteria for PJS should undergo genetic testing for a mutation in the STK11 gene. Genetic testing in an individual meeting the clinical criteria serves to confirm the diagnosis of PJS. However, the absence of a pathogenic STK11 mutation in an individual meeting the clinical criteria does not exclude the diagnosis.

PJS can be distinguished from other disorders involving pigmented mucocutaneous macules or multiple hamartomatous gastrointestinal polyps on the basis of clinical manifestations and/or genetic testing.

Disease Management – Our approach to cancer screening in individuals with PJS is as follows:

• An annual physical examination with a complete blood count to detect iron deficiency anemia due to occult bleeding from gastrointestinal polyps or cancer.
• Baseline screening of the stomach and colon with upper endoscopy and colonoscopy every two to three years starting in the late teens.
• Baseline endoscopic screening of the small bowel with video capsule endoscopy (VCE) between ages eight and ten. The follow-up interval is based on the findings. In the absence of polyps, however, follow-up screening is recommended at age 18, followed by repetition every two to three years. Computed tomography enterography (CTE) or magnetic resonance enterography (MRE) are alternative imaging methods for individuals with PJS who cannot undergo capsule endoscopy.
• An annual examination of the testes from age 10. Testicular ultrasound should be performed if abnormalities are detected on examination or if patients have signs of feminization (for example, gynecomastia).
• An annual pelvic examination and Pap smear in women from age 21.
• Monthly breast self-examination for women and annual breast magnetic resonance imaging (MRI) and mammography from age 25.
• For pancreatic cancer screening, MRI/magnetic resonance cholangiopancreatography or endoscopic ultrasonography of the pancreas every 1-2 years from age 35. Pancreatic cancer screening should be performed at specialist centers where a research protocol will be established.
• Individuals with an STK11 mutation should be offered the option of preimplantation genetic diagnosis during preconception counseling. First-degree relatives of patients with PJS should be screened for its clinical features from birth. Screening consists of an annual history, a physical examination including assessment of mucocutaneous pigmentation, and assessment of signs of early puberty. Male patients should also be examined for signs of feminization (such as gynecomastia) and for testicular tumors by palpation of the testes. Predictive genetic testing should be offered by age eight to at-risk individuals whose diagnosis is not clinically apparent, provided that a pathogenic STK11 mutation has been identified in an affected family member.