Peutz–Jeghers syndrome

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Peutz-Jeghers syndrome
Classification and external resources
Peutz-Jeghers syndrome polyp.jpg
Micrograph of Peutz-Jeghers type colonic polyp. H&E stain.
ICD-10 Q85.8
ICD-9 759.6
OMIM 175200
DiseasesDB 9905
MedlinePlus 000244
eMedicine med/1807 article/182006article/1664349
MeSH D010580
GeneReviews

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 (melanosis).[1] Peutz–Jeghers syndrome has an incidence of approximately 1 in 25,000 to 300,000 births.[2]

Diagnosis[edit]

The main criteria for clinical 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.

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. 90-100% of patients with a clinical diagnosis of PJS have a mutation in the STK11/LKB1 gene. Molecular genetic testing for this mutation is available clinically.[3]

Natural history[edit]

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

Most patients will develop flat, brownish spots (melanotic macules) on the skin, especially on the lips and oral mucosa, during the first year of life, and a patient’s first bowel obstruction due to intussusception usually occurs between the ages of six and 18 years. The 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.[citation needed]

Genetics[edit]

In 1998, a gene was found to be associated with the mutation. On chromosome 19, the gene known as STK11 (LKB1)[4] is a possible tumor suppressor gene. It is inherited in an autosomal dominant pattern, which means that anyone who has PJS has a 50% chance of passing the disease on to their offspring.[citation needed]

Limited evidence base[edit]

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 due 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.[5]

Presentation[edit]

The risks associated with this syndrome include a strong tendency of developing cancer in a number of parts of the body.[6] While the hamartomatous polyps themselves only have a small malignant potential (<3% - OHCM), patients with the syndrome have an increased risk of developing carcinomas of the pancreas,[7] liver, lungs, breast, ovaries, uterus, testicles and other organs.[citation needed]

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.[citation needed]

Cancer screening[edit]

Barium enema radiograph showing multiple polyps (mostly pedunculated) and at least one large mass at the hepatic flexure coated with contrast in a patient with Peutz–Jeghers syndrome.

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) from age 25 annually livelong,[3] 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.[citation needed]

Treatment[edit]

Resection of the polyps is required only if serious bleeding or intussusception occurs. Enterotomy is performed for removing large, single nodules. Short lengths of heavily involved intestinal segments can be resected. Colonoscopy can be used to snare the polyps if they are within reach.[citation needed]

Eponym[edit]

It is named after Johannes Laurentius Augustinus Peutz (1886 – 1957), a Dutch Internist who worked in Ohio, USA together with his co internist, Harold Joseph Jeghers (1904-1990).

See also[edit]

References[edit]

  1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 857. ISBN 0-7216-2921-0. 
  2. ^ Bouquot, Jerry E.; Neville, Brad W.; Damm, Douglas D.; Allen, Carl P. (2008). Oral and Maxillofacial Pathology. Philadelphia: Saunders. p. 16.11. ISBN 1-4160-3435-8. 
  3. ^ a b McGarrity, Thomas J; Amos, Christopher I; Frazier, Marsha L; Wei, Chongjuan (July 25, 2013). "Peutz-Jeghers Syndrome". In Pagon, Roberta A; Adam, Margaret P; Bird, Thomas D; Dolan, Cynthia R; Fong, Chin-To; Smith, Richard JH; Stephens, Karen. GeneReviews. Seattle: University of Washington. PMID 20301443. 
  4. ^ Q15831
  5. ^ Riegert-Johnson, Douglas; Gleeson, Ferga C.; Westra, Wytske; Hefferon, Timothy; Song, Louis M. Wong Kee; Spurck, Lauren; Boardman, Lisa A. (August 9, 2008). "Peutz-Jeghers Syndrome". In Riegert-Johnson, Douglas L; Boardman, Lisa A; Hefferon, Timothy; Roberts, Maegan. Cancer Syndromes. 
  6. ^ Boardman, Lisa A.; Thibodeau, Stephen N.; Schaid, Daniel J.; Lindor, Noralane M.; McDonnell, Shannon K.; Burgart, Lawrence J.; Ahlquist, David A.; Podratz, Karl C.; Pittelkow, Mark; Hartmann, Lynn C. (1998). "Increased Risk for Cancer in Patients with the Peutz-Jeghers Syndrome". Annals of Internal Medicine 128 (11): 896–9. doi:10.7326/0003-4819-128-11-199806010-00004. PMID 9634427. 
  7. ^ Ryan DP, Hong TS, Bardeesy N (September 2014). "Pancreatic adenocarcinoma". N. Engl. J. Med. 371 (11): 1039–49. doi:10.1056/NEJMra1404198. PMID 25207767. 

External links[edit]