Peutz–Jeghers syndrome
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| Peutz-Jeghers syndrome | |
| Classification and external resources | |
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|---|---|
| ICD-10 | Q85.8 |
| ICD-9 | 759.6 |
| OMIM | 175200 |
| DiseasesDB | 9905 |
| eMedicine | med/1807 |
| MeSH | D010580 |
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.[1]:857 Peutz-Jegher syndrome has a prevalence of approximately 1 in 100,000 to 200,000 births [2]
Contents |
[edit] 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 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 gene.
[edit] Natural History
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.
[edit] Genetics
In 1998, a gene was found to be associated with the mutation. On chromosome 19, the gene known as STK11 (LKB1)[3] 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.
[edit] 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. [4]
[edit] Presentation
The risks associated with this syndrome include a strong tendency of developing cancer in multiple sites[5]. 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.
Most of the data regarding this disorder are from selected family lines and thus the risks endured by those families regarding outcomes may not translate completely to the patient without a familial history.
[edit] Prognosis
Almost half of Peutz-Jeghers patients die from cancer by age 57 years, and the cumulative risk of developing a form of cancer associated with Peutz-Jeghers syndrome between ages 15–64 is 93%.[6]
[edit] Screening
Screening includes upper GI endoscopy, enteroclysis, and colonoscopy to check for the locations of the hamartomas. To check for cancerous lesions, endoscopic ultrasound, testicular ultrasound and imaging studies of the liver and the pancreas are indicated because of the risk of pancreatic cancer as well as gallbladder polyps and cancer. These imaging studies may include ultrasonography as well as CT with pancreatic details or magnetic resonance cholangiopancreatography (MRCP).
In addition, an annual physical examination that includes evaluation of the breasts, abdomen, pelvis, and testes should be done by a physician. An annual complete blood count to check for anemia should be done. If bleeding is found, removal of hemorrhagic or large polyps (>5 mm) by endoscopic polypectomy should be performed.
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.[7]
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, gynecological consultations are often needed.
[edit] See also
[edit] References
- ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0721629210.
- ^ Neville, Brad. Oral and Maxillofacial Pathology, 3rd Edition. Saunders Book Company, 062008. 16.11
- ^ "UniProtKB/Swiss-Prot entry Q15831 [STK11_HUMAN Serine/threonine-protein kinase 11]". http://us.expasy.org/cgi-bin/niceprot.pl?Q15831. Retrieved on 2007-07-21.
- ^ Peutz-Jeghers Syndrome. In: Familial Cancer Syndromes. DL Riegert-Johnson and others. NCBI 2009 [1]
- ^ Boardman LA, Thibodeau SN, Schaid DJ, et al. (1998). "Increased risk for cancer in patients with the Peutz-Jeghers syndrome". Ann. Intern. Med. 128 (11): 896–9. PMID 9634427.
- ^ "eMedicine - Peutz-Jeghers Syndrome : Article by Andrea Duchini, MD". http://www.emedicine.com/med/topic1807.htm. Retrieved on 2007-07-21.
- ^ Peutz-Jeghers Syndrome. In: Familial Cancer Syndromes. DL Riegert-Johnson and others. NCBI 2009 [2]
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