Peutz–Jeghers syndrome

Peutz-Jeghers syndrome
Micrograph of Peutz-Jeghers type colonic polyp. H&E stain.
Classification and external resources
Specialty	medical genetics
ICD-10	Q85.8
ICD-9-CM	759.6
OMIM	175200
DiseasesDB	9905
MedlinePlus	000244
eMedicine	med/1807 article/182006 article/1664349
MeSH	D010580
GeneReviews	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 (melanosis).^[1] Peutz–Jeghers syndrome has an incidence of approximately 1 in 25,000 to 300,000 births.^[2]

Diagnosis

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

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.

Genetics

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.

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 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

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.

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

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 smear (Pap smear) 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.

Treatment

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.

Eponym

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).

References

↑ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 857. ISBN 0-7216-2921-0.
↑ 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.
1 2 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.
↑ Q15831
↑ 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.
↑ 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.
↑ 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

Wikimedia Commons has media related to Peutz–Jeghers syndrome.

GeneReviews/NCBI/NIH/UW entry on Peutz-Jeghers syndrome
Peutz-Jeghers syndrome - Genetics Home Reference

Phakomatosis (Q85, 759.5–759.6)

Neurofibromatosis	Type I Type II

Angiomatosis	Sturge–Weber syndrome Von Hippel–Lindau disease

Hamartoma	Tuberous sclerosis Hypothalamic hamartoma (Pallister–Hall syndrome) Multiple hamartoma syndrome Proteus syndrome Cowden syndrome Bannayan–Riley–Ruvalcaba syndrome Lhermitte–Duclos disease

Other	Abdallat–Davis–Farrage syndrome Ataxia telangiectasia Incontinentia pigmenti Peutz–Jeghers syndrome

Digestive system neoplasia (C15–C26/D12–D13, 150–159/211)

GI tract

Upper

Esophagus	Squamous cell carcinoma Adenocarcinoma

Stomach	Gastric carcinoma Signet ring cell carcinoma Gastric lymphoma MALT lymphoma Linitis plastica

Lower

Small intestine	Duodenal cancer Adenocarcinoma

Appendix	Carcinoid Pseudomyxoma peritonei

Colon/rectum	colorectal polyp: Peutz–Jeghers syndrome Juvenile polyposis syndrome Familial adenomatous polyposis/Gardner's syndrome Cronkhite–Canada syndrome neoplasm: Adenocarcinoma Familial adenomatous polyposis Hereditary nonpolyposis colorectal cancer

Anus	Squamous cell carcinoma

Upper and/or lower

Accessory

Liver	malignant: Hepatocellular carcinoma Fibrolamellar Hepatoblastoma benign: Hepatocellular adenoma Cavernous hemangioma hyperplasia: Focal nodular hyperplasia Nodular regenerative hyperplasia

Biliary tract	bile duct: Cholangiocarcinoma Klatskin tumor gallbladder: Gallbladder cancer

Pancreas	exocrine pancreas: Adenocarcinoma Pancreatic ductal carcinoma cystic neoplasms: Serous microcystic adenoma Intraductal papillary mucinous neoplasm Mucinous cystic neoplasm Solid pseudopapillary neoplasm Pancreatoblastoma

Peritoneum

Deficiencies of intracellular signaling peptides and proteins

GTP-binding protein regulators

GTPase-activating protein	Neurofibromatosis type I Watson syndrome Tuberous sclerosis

Guanine nucleotide exchange factor	Marinesco–Sjögren syndrome Aarskog–Scott syndrome Juvenile primary lateral sclerosis X-Linked mental retardation 1

G protein

Heterotrimeic	cAMP/GNAS1: Pseudopseudohypoparathyroidism Progressive osseous heteroplasia Pseudohypoparathyroidism Albright's hereditary osteodystrophy McCune–Albright syndrome CGL 2

Monomeric	RAS: HRAS Costello syndrome KRAS Noonan syndrome 3 KRAS Cardiofaciocutaneous syndrome RAB: RAB7 Charcot–Marie–Tooth disease RAB23 Carpenter syndrome RAB27 Griscelli syndrome type 2 RHO: RAC2 Neutrophil immunodeficiency syndrome ARF: SAR1B Chylomicron retention disease ARL13B Joubert syndrome 8 ARL6 Bardet–Biedl syndrome 3

MAP kinase

Cardiofaciocutaneous syndrome

Other kinase/phosphatase

Tyrosine kinase	BTK X-linked agammaglobulinemia ZAP70 ZAP70 deficiency

Serine/threonine kinase	RPS6KA3 Coffin-Lowry syndrome CHEK2 Li-Fraumeni syndrome 2 IKBKG Incontinentia pigmenti STK11 Peutz–Jeghers syndrome DMPK Myotonic dystrophy 1 ATR Seckel syndrome 1 GRK1 Oguchi disease 2 WNK4/WNK1 Pseudohypoaldosteronism 2

Tyrosine phosphatase	PTEN Bannayan–Riley–Ruvalcaba syndrome Lhermitte–Duclos disease Cowden syndrome Proteus-like syndrome MTM1 X-linked myotubular myopathy PTPN11 Noonan syndrome 1 LEOPARD syndrome Metachondromatosis

Signal transducing adaptor proteins

Other

NF2
- Neurofibromatosis type II
NOTCH3
- CADASIL
PRKAR1A
- Carney complex
PRKAG2
- Wolff–Parkinson–White syndrome
PRKCSH
- PRKCSH Polycystic liver disease
XIAP
- XIAP2

See also intracellular signaling peptides and proteins

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