Goodlettsville Dental Services

Peutz–Jeghers Syndrome

Peutz–Jeghers syndrome, also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa. Peutz-Jegher syndrome has a prevalence of approximately 1 in 25,000 to 300,000 births

Diagnosis

The main criteria for diagnosis are:

• Family history  
• Mucocutaneous lesions causing patches of hyperpigmentation in the mouth and on the hands and feet. The oral pigmentations are the first on the body to appear, and thus play an important part in early diagnosis. Intraorally, they are most frequently seen on the gingiva, hard palate and inside of the cheek. The mucosa of the lower lip is almost invariably involved as well.  
• Hamartomatous polyps in the gastrointestinal tract. These are benign polyps with an extraordinarily low potential for malignancy.  
• Mutation in the STK11/LKB1 gene.  

Having 2 of the 3 listed clinical criteria indicates a positive diagnosis. The oral findings are consistent with other conditions, such as Addison’s disease and McCune-Albright syndrome, and these should be included in the differential diagnosis. Definitive diagnosis requires a histological sample of a polyp or a identification of a mutation in the STK11 (also known as LKB1) gene.

Natural history

Most people with Peutz-Jeghers syndrome will have developed some form of neoplastic disease by age 60

Most patients will develop melanotic macules during the first year of life and a patient’s first intussusception usually occurs between the ages of six and 18 years old. Cumulative lifetime cancer risk begins to rise in middle age. Cumulative risks by age 70 for all cancers, gastrointestinal (GI) cancers, and pancreatic cancer are 85%, 57%, and 11%, respectively.

Genetics

In 1998, a gene was found to be associated with the mutation. On chromosome 19, the gene known as STK11 (LKB1) is a possible tumor suppressor gene. It is inherited in an autosomal-dominant pattern (see Mendelian inheritance) which means that anyone who has PJS has a 50% chance of passing it onto their children.

Limited evidence base

Peutz-Jeghers syndrome is rare and studies typically include only a small number of patients. Even in those few studies that do contain a large number of patients, the quality of the evidence is limited do to pooling patients from many centers, selection bias (only patients with health problems coming from treatment are included), and historical bias (the patients reported are from a time before advances in the diagnosis of treatment of Peutz-Jeghers syndrome were made). Probably due to this limited evidence base, cancer risk estimates for Peutz-Jeghers syndrome vary from study to study.

Presentation

The risks associated with this syndrome include a strong tendency of developing cancer in multiple sites. While the harmartomatous polyps themselves only have a small malignant potential (<3% – OHCM), patients with the syndrome have an increased risk of developing carcinomas of the pancreas, liver, lungs, breast, ovaries, uterus, testicles and other organs.

The average age of first diagnosis is 23, but the lesions can be identified at birth by an astute pediatrician. Prior to puberty, the mucocutaneous lesions can be found on the palms and soles. Often the first presentation is as a bowel obstruction from an intussusception which is a common cause of mortality; an intussusception is a telescoping of one loop of bowel into another segment.

Cancer screening

The three clinical centers with the most experience treating Peutz-Jeghers patients are probably Johns Hopkins (Baltimore, Maryland), St. Mark’s Hospital (Harrow, UK) and Mayo Clinic (Jacksonville, Florida; Rochester, Minnesota). Each has developed their own cancer surveillance protocol.

Some suggestions for surveillance for cancer include the following:

• Small intestine with small bowel radiography every 2 years,  
• Esophagogastroduodenoscopy and colonoscopy every 2 years,  
• CT scan or MRI of the pancreas yearly,  
• Ultrasound of the pelvis (women) and testes (men) yearly,  
• Mammography (women) at ages 25, 30, 35, and 38 years, then every 2 years until age 50 years, then annually, and  
• Papanicolaou (Pap) test every year  

Follow-up care should be supervised by a physician familiar with Peutz-Jeghers syndrome. Genetic consultation and counseling as well as urological and gynecological consultations are often needed.