Peutz-Jeghers syndrome (PJS) is an inherited condition that puts people at an increased risk for developing hamartomatous polyps in the digestive tract as well . El síndrome de Peutz-Jeghers es una rara enfermedad hereditaria, aunque se ha descrito hasta un 20 % de casos esporádicos. Clínicamente se diagnostica. El síndrome de Peutz-Jeghers es un raro proceso hereditario que suele iniciarse en la infancia. Se caracteriza por la presencia de lesiones cutáneas.
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CC HPO: Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by melanocytic macules of the lips, buccal mucosa, and digits; multiple gastrointestinal hamartomatous polyps; and an increased risk of various neoplasms. In the syndrome named for Peutz and Jeghers Jeghers et al.
Intussusception and bleeding are the usual symptoms. Melanin spots of the lips, buccal mucosa, and digits represent the second part of the syndrome.
Malignant degeneration of the small intestinal polyps is rare. Metastases from a malignant polyp in Peutz-Jeghers syndrome was reported by Williams and Knudsen In the family reported by Farmer et al. Hamartomatous polyps were limited to the jejunum and caused bleeding. Griffith and Bisset reported 3 cases. In 2 of them, the family history was negative; in the third, the father and a paternal uncle had melanin spots of the lips but no history of intestinal disorder.
Sommerhaug and Encermedad added the ureter to the sites of polyps described in the Peutz-Jeghers syndrome. Previously described extraintestinal sites include esophagus, bladder, renal pelvis, bronchus and nose.
Burdick and Prior reported nonresectable adenocarcinoma of the jejunum arising in a Peutz-Jeghers polyp and accompanied by metastases in mesenteric lymph nodes. Two developed breast carcinoma of which 1 arose in a fibroadenoma.
Three had benign ovarian tumors, 1 had a benign breast tumor and 1 had a benign colloid thyroid nodule. One of the cases case 7 reported by Jeghers et al.
Bowlby reported pancreatic cancer in an adolescent boy with PJS. Affected females are prone to develop ovarian tumor, especially granulosa cell tumor Christian et al. The testicular tumors appear to be of Sertoli peugz-jeghers origin and most are calcifying. Two previously reported cases were found.
Studies led to the conclusion that increase in aromatase activity in the gonadal tumors was responsible for estrogen excess and gynecomastia. Three other reported male patients with Peutz-Jeghers syndrome and gonadal tumors had presented with gynecomastia between birth and 6 years of age. They pointed out that multifocal sex-cord tumors were found in palpably normal testes.
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The occurrence of ovarian tumors far exceeds that of testicular tumors in this disorder. The production of estrogen by ovarian tumors is indicated by the reported appearance of isosexual precocity in girls with PJS Solh et al. Both had rapid growth and advanced bone age, and serum levels of estradiol were markedly elevated. Enfermfdad a patient with both psoriasis and Peutz-Jeghers syndrome sine polypsBanse-Kupin and Douglass described a peculiar phenomenon: Sommerhaug and Mason suggested that patients with PJS develop polyps in areas of frequent trauma.
Banse-Kupin and Douglass proposed that pigmented macules may likewise be located in areas of frequent trauma or areas of inflammation. Inflammation may induce blockage of pigment transfer from melanocyte to keratinocyte, resulting in a macule. As the inflammation or trauma subsides, so may the blockage and the lesion may fade. Histologically, the oral mucosal lesions resemble lentigo simplex, but the acral lesions are distinctive Yamada et al.
There is an increased number of melanocytes with long dendrites filled with melanosomes but few melanosomes in keratocytes, suggesting a pigment block. Gastrointestinal carcinoma developed in 4, nongastrointestinal carcinoma in 10, and multiple myeloma in 1. Adenomatous polyps of the stomach and colon occurred in 3 other patients. There were 4 cases of pancreatic cancer. The family had also been studied earlier by Bartholomew et al.
In all, 12 affected members peutz-eghers been identified, making this the largest PJS kindred reported. One member of the family fe developed a duodenal carcinoma and a hamartoma with adenomatous changes. Another member developed short bowel syndrome. In the follow-up of 72 patients with PJS in the St. Mark’s Polyposis Registry, Spigelman et al. There were 9 gastrointestinal and 7 nongastrointestinal tumors.
The risks imposed by polyps included surgical emergencies like small bowel intussusception, and chronic or acute bleeding from the polyps. Many reports, however, suggested an association of PJS with both gastrointestinal and nongastrointestinal malignancies, often at a young age.
Orphanet: Peutz Jeghers syndrome
peutz-jegherss The frequent occurrence of rare tumors of the ovary, cervix, and testis indicated a general susceptibility for the development of malignancies. The PJS gene was therefore thought to act as a tumor suppressor gene. The authors suggested that a surveillance protocol should be developed for the prevention of cancer in PJS. Unusually early age of onset was observed by Fernandez Seara et al.
At 15 days of age, ileocecal intussusception causing intestinal obstruction was diagnosed radiologically and reduced by hydrostatic enema; ileocecal surgical resection was required, however. Rectal prolapse due to a large polyp occurred at one month of age. Esophagogastroscopy peutz-jegherd polyps in the stomach; one in the antrum partially obstructed the lumen.
No peutz-jegherd of the lips or oral mucosa was observed at any time and none was present in her relatives. The histologic appearance of the polyps removed during life and at autopsy was consistent with Peutz-Jeghers syndrome. PJS hamartomas show an elongated, frond-like epithelium with cystic dilatation of glands overlying an arborizing network of smooth muscle bundles.
Hypermucinous goblet cells are often prominent. In addition, pseudoinvasion by histopathologically benign epithelium is common in Peytz-jeghers hamartomas. These characteristic features are easily distinguished from the cytologic atypia and lack of differentiation seen in typical adenomas, and it is not surprising that PJS tumors seem to share few of the earliest genetic events observed in the transition of normal epithelium to dysplastic adenomas.
The hamartomas of juvenile polyposis are histologically distinct from those of PJS, and the risk of malignancy also differs in these 2 syndromes. Some patients with PJS may peutz-jegherx disturbed by the appearance of lentigines.
Peutz–Jeghers syndrome – Wikipedia
They stated that the response to treatment was excellent, with no sequelae or recurrence pejtz-jeghers the lesions. Oral pigmentation tends to fade and be forgotten with time, and polyps can often be asymptomatic. Additionally, other syndromes may mimic the pigmentation of PJS, occurring in individuals with an occult malignancy Babin et al. Pigmented spots occur also in BRRS but characteristically on the glans penis in males and not on the lips.
In connection with the possibility that the melanin spots of the lips represent a benign neoplasm, the observations of Jeghers et al. The pigmentation occurred mainly in vertical bands interrupted by unpigmented areas. The change suggested the possibility of clonality. Studying 2 extended families, Bali et al. Seldin reported that addition of more family members in the 2 largest families decreased the lod scores substantially as did the addition of more peuzt-jeghers in the region.
Indeed, in the original study, the maximum 2-point lod was below 2. Multipoint linkage analysis yielded a maximum lod score of 4. This is located in the distal region of 1p, where the human homolog of the putative modifier of multiple intestinal neoplasias had previously been mapped. In enfermeda patient with Peutz-Jeghers syndrome, Markie et al.
Using fluorescence in situ hybridization with YAC clones selected to contain genetic markers from chromosome 6 and with a probe for the centromeric alphoid array, they located 1 inversion breakpoint within the alphoid repeat array, in a 1-cM interval between D6S and D6S, and the other in a 4-cM interval between D6S and D6S To localize the susceptibility locus for Peutz-Jeghers syndrome, Hemminki et al.
They demonstrated a high-penetrance locus in distal 19p with a multipoint lod score of 7. In comparative genomic hybridization, a single hybridization allows DNA copy number changes in the whole genome of a tumor to be assessed in peutz-jegherd with normal tissue DNA Kallioniemi enfermevad al.
The findings of Hemminki et al. That the Peutz-Jeghers syndrome is genetically homogeneous required, however, confirmation by linkage analysis in further families. In the 5 families examined, there were no recombinants with the marker D19S The multipoint lod score at D19S was 7.
Marker D19S yielded a maximum lod score of 4. However, markers on 19q For example, D19S resulted in a maximum lod score of 3. Most of this positive linkage was contributed by a single family.
Thus, the results confirmed the mapping of a common PJS locus on 19p Within a distance of kb proximal to D19S, the marker with the highest lod score in the study of Hemminki et al. In a 3-generation PJS family, they found an STK11 allele with a deletion of exons 4 and 5 and an inversion of exons 6 and 7 All 5 germline mutations were predicted to disrupt the function of the kinase domain.
Independently and simultaneously, Hemminki et al. Jenne speculated that cellular context between melanocytes and keratinocytes are regulated by STK11 activity.
He pointed to the wide tissue distribution of STK11 and suggested that effects in melanocytes may be observed preferentially at sites of mechanical and physical stress. Linkage analysis in the family studied by McKusick, who contributed to the publication of Jeghers et al. Haplotype analysis indicated that the retained allele carried a germline mutation LOH of 17p and 18q was identified in an adenocarcinoma but not in hamartomas, enfermeda that allelic loss of these 2 regions corresponds to late molecular events in the pathogenesis of cancer in PJS.
The adenocarcinomas showing 17p LOH also demonstrated altered p53 by immunohistochemistry.
These data provided evidence that STK11 is a tumor suppressor gene that acts as an early gatekeeper regulating the development of hamartomas in PJS and suggested that hamartomas may be pathogenetic precursors of adenocarcinoma.
Additional somatic mutation events underlie the progression of hamartomas to adenocarcinomas, and some of these somatic mutations are common to the later stages of tumor progression seen in the majority of colorectal carcinomas.