Peutz-Jeghers syndrome
Encyclopedia
Peutz–Jeghers syndrome, also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartoma
tous polyps
in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa. Peutz–Jeghers syndrome has an incidence of approximately 1 in 25,000 to 300,000 births
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.
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.
, 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, assuming that their spouse does not have the disease.
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.
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.
Hamartoma
A hamartoma is a benign, focal malformation that resembles a neoplasm in the tissue of its origin. This is not a malignant tumor, and it grows at the same rate as the surrounding tissues. It is composed of tissue elements normally found at that site, but which are growing in a disorganized mass...
tous polyps
Polyp (medicine)
A polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated. If no stalk is present, it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, sinus, urinary bladder...
in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa. Peutz–Jeghers syndrome has an incidence of approximately 1 in 25,000 to 300,000 births
Diagnosis
The main criteria for clinical diagnosis are:- Family historyFamily history (medicine)In medicine, a family history consists of information about disorders from which the direct blood relatives of the patient have suffered. Genealogy typically includes very little of the medical history of the family, but the medical history could be considered a specific subset of the total 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 polypsPolyp (medicine)A polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated. If no stalk is present, it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, sinus, urinary bladder...
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
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
and McCune-Albright syndrome
McCune-Albright syndrome
McCune–Albright syndrome, described in 1937 by Donovan James McCune and Fuller Albright, is a genetic disorder of bones, skin pigmentation and hormonal problems along with premature puberty.-Symptoms:...
, and these should be included in the differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
. 90-100% of patients with a clinical diagnosis of PJS have a mutation in the STK11
STK11
Serine/threonine kinase 11 also known as liver kinase B1 or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the STK11 gene.-Expression:...
/LKB1 gene. Molecular genetic testing for this mutation is available clinically.
Natural history
Most patients will develop flat, brownish spots (melanotic macules) on the skin during the first year of life, and a patient’s first bowel obstruction due to intussusceptionIntussusception (medical disorder)
An intussusception is a medical condition in which a part of the intestine has invaginated into another section of intestine, similar to the way in which the parts of a collapsible telescope slide into one another. This can often result in an obstruction...
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 19Chromosome 19 (human)
125px|rightChromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 63 million base pairs and represents between 2 and 2.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active...
, the gene known as STK11
STK11
Serine/threonine kinase 11 also known as liver kinase B1 or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the STK11 gene.-Expression:...
(LKB1) is a possible tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
. It is inherited in an autosomal-dominant pattern (see Mendelian inheritance
Mendelian inheritance
Mendelian inheritance is a scientific description of how hereditary characteristics are passed from parent organisms to their offspring; it underlies much of genetics...
) which means that anyone who has PJS has a 50% chance of passing it onto their children, assuming that their spouse does not have the disease.
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.Presentation
The risks associated with this syndrome include a strong tendency of developing cancer in multiple sites. 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, 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
Intussusception (medical disorder)
An intussusception is a medical condition in which a part of the intestine has invaginated into another section of intestine, similar to the way in which the parts of a collapsible telescope slide into one another. This can often result in an obstruction...
which is a common cause of mortality; an intussusception is a telescoping of one loop of bowel into another segment.
Cancer screening
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, 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.
External links
- GeneReviews/NCBI/NIH/UW entry on Peutz-Jeghers syndrome
- OMIM entries on Peutz-Jeghers syndrome
- Peutz-Jeghers syndrome - MedlinePlusMedlinePlusMedlinePlus is a free Web site that provides consumer health information for patients, families, and Health care providers. The site brings together information from the United States National Library of Medicine, the National Institutes of Health , other U.S. government agencies, and...
Medical Encyclopedia - Peutz-Jeghers syndrome - Genetics Home Reference
- Peutz-Jeghers Syndrome - eMedicineEMedicineeMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely, two medical doctors. The website is searchable by keyword and consists of approximately 6,800 articles, each of which is associated with one of 62 clinical subspecialty textbooks...
- Peutz-Jeghers Syndrome- eMedicineEMedicineeMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely, two medical doctors. The website is searchable by keyword and consists of approximately 6,800 articles, each of which is associated with one of 62 clinical subspecialty textbooks...
- Peutz-Jeghers Syndrome
- http://www.polyposisregistry.org.uk/