Peutz–Jeghers syndrome (often abbreviated PJS) is an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

characterized by the development of benign

hamartoma A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended f ...

tous polyps in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

and hyperpigmented macules on the

lip The lips are the visible body part at the mouth of many animals, including humans. Lips are soft, movable, and serve as the opening for food intake and in the articulation of sound and speech. Human lips are a tactile sensory organ, and can be ...

s and

oral mucosa The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been de ...

( melanosis). This

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...

can be classed as one of various

hereditary Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic informa ...

intestinal polyposis syndromes and one of various hamartomatous polyposis syndromes. It has an incidence of approximately 1 in 25,000 to 300,000 births.

Signs and symptoms

The risks associated with this syndrome include a substantial risk of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

, especially of the breast and gastrointestinal tracts. Colorectal is the most common malignancy, with a lifetime risk of 39 percent, followed by breast cancer in females with a lifetime risk of 32 to 54 percent. Patients with the syndrome also have an increased risk of developing carcinomas of the liver, lungs, breast, ovaries, uterus, testes, and other organs. Specifically, it is associated with an increased risk of sex-cord stromal tumor with annular tubules in the ovaries. Due to the increased risk of malignancies, direct surveillance is recommended. Peutz-Jeghers syndrome polyp

The average age of first diagnosis is 23. The first presentation is often bowel obstruction or intussuseption from the hamartomatous gastrointestinal polyps. Dark blue, brown, and black pigmented mucocutaneous macules, are present in over 95 percent of individuals with Peutz-Jeghers syndrome. Pigmented lesions are rarely present at birth, but often appear before 5 years of age. The macules may fade during puberty. The melanocytic macules are not associated with malignant transformation. Complications associated with Peutz-Jeghers syndrome include obstruction and intussusception, which occur in up to 69 percent of patients, typically first between the ages of 6 and 18, though surveillance for them is controversial. Anemia is also common due to gastrointestinal bleeding from the polyps.

Genetics

In 1998, a gene was found to be associated with the mutation. On

chromosome 19 Chromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 58.6 million base pairs, the building material of DNA. It is considered the most gene-rich chromos ...

, the gene known as ''

STK11 Serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the ''STK11'' gene. Expression Testosterone (medication), Testosterone and Dihydrotestos ...

'' (''LKB1'') is a possible

tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or re ...

. It is inherited in an

pattern, which means that anyone who has PJS has a 50% chance of passing the disease on to their offspring. 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. There is an estimated 18–21% risk of ovarian cancer, 9% risk of endometrial cancer, and 10% risk of cervical cancer, specifically adenoma malignum.

Diagnosis

The main criteria for clinical diagnosis are: *

Family history Genealogy () is the study of families, family history, and the tracing of their lineages. Genealogists use oral interviews, historical records, genetic analysis, and other records to obtain information about a family and to demonstrate kin ...

* 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 A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...

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 Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrena ...

and

McCune–Albright syndrome McCune–Albright syndrome is a complex genetic disorder affecting the bone, skin and endocrine systems. It is a mosaic disease arising from somatic activating mutations in '' GNAS'', which encodes the alpha-subunit of the Gs heterotrimeric G ...

, and these should be included in the

differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...

. 90–100% of patients with a clinical diagnosis of PJS have a mutation in the ''

LKB1 Serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the ''STK11'' gene. Expression Testosterone and DHT treatment of murine 3T3-L1 or hu ...

'' gene. Molecular genetic testing for this mutation is available clinically.

Management

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.

Prognosis

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 The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

obstruction due to

intussusception Intussusception may refer to: * Intussusception (medical disorder) Intussusception is a medical condition in which a part of the intestine folds into the section immediately ahead of it. It typically involves the small bowel and less commonly ...

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. A 2011 Dutch study followed 133 patients for 14 years. The cumulative risk for cancer was 40% and 76% at ages 40 and 70, respectively. 42 (32%) of the patients died during the study, of which 28 (67%) were cancer related. They died at a median age of 45. Mortality was increased compared with the general population. A family with sinonasal polyposis were followed up for 28 years. Two cases of sinonasal type adenocarcinoma developed. This is a rare cancer. This report suggested that follow up of sinus polyps in this syndrome may be indicated.Chiang JM, Chen TC (2017) A Peutz-Jeghers syndrome family associated with sinonasal adenocarcinoma: 28 years follow up report. Fam Cancer doi: 10.1007/s10689-017-9983-z.

Monitoring

Multiple polyps and at large mass at the hepatic flexure

Some suggestions for surveillance for cancer include the following: * Small intestine with small bowel radiography every 2 years, *

Esophagogastroduodenoscopy Esophagogastroduodenoscopy (EGD) or oesophagogastroduodenoscopy (OGD), also called by various other names, is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract down to the duodenum. It is considered ...

and

colonoscopy Colonoscopy () or coloscopy () is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It can provide a visual diagnosis ('' ...

every 2 years, * CT scan or MRI of the pancreas yearly, * Ultrasound of the pelvis and testes yearly *

Mammography Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through ...

from age 25 annually *

Papanicolaou smear The Papanicolaou test (abbreviated as Pap test, also known as Pap smear (AE), cervical smear (BE), cervical screening (BE), or smear test (BE)) is a method of cervical screening used to detect potentially precancerous and cancerous processes in t ...

(Pap smear) annually beginning at age 18-20 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.

Eponym

First described in a published case report in 1921 by Jan Peutz (1886–1957), a Dutch Internist, it was later formalized into the syndrome by American physicians at Boston City Hospital, Harold Joseph Jeghers (1904–1990) and Kermit Harry Katz (1914–2003), and Victor Almon McKusick (1921–2008) in 1949 and published in the ''New England Journal of Medicine''.Familial Cancer 2002; 1:181–185)

References

External links

GeneReviews/NCBI/NIH/UW entry on Peutz-Jeghers syndrome

Peutz-Jeghers syndrome
– Genetics Home Reference {{DEFAULTSORT:Peutz-Jeghers Syndrome Autosomal dominant disorders Gastrointestinal tract disorders Deficiencies of intracellular signaling peptides and proteins Gynaecological neoplasia Syndromes affecting the gastrointestinal tract Urological conditions Disturbances of human pigmentation Melanocytic nevi and neoplasms Oral mucosal pathology