RESUMEN
BACKGROUND: Peutz-Jeghers syndrome (PJS) is caused by germline STK11 mutations and characterised by gastrointestinal polyposis. Although small bowel intussusception is a recognised complication of PJS, risk varies between patients. OBJECTIVE: To analyse the time to onset of intussusception in a large series of PJS probands. METHODS: STK11 mutation status was evaluated in 225 PJS probands and medical histories of the patients reviewed. RESULTS: 135 (60%) of the probands possessed a germline STK11 mutation; 109 (48%) probands had a history of intussusception at a median age of 15.0 years but with wide variability (range 3.7 to 45.4 years). Median time to onset of intussusception was not significantly different between those with identified mutations and those with no mutation detected, at 14.7 years and 16.4 years, respectively (log-rank test of difference, chi(2) = 0.58, with 1df; p = 0.45). Similarly no differences were observed between patient groups on the basis of the type or site of STK11 mutation. CONCLUSIONS: The risk of intussusception in PJS is not influenced by STK11 mutation status.
Asunto(s)
Intususcepción/genética , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinasas/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Café-au-lait spots (CALS) are classically found in neurocutaneous syndromes such as neurofibromatosis, but have not been associated with hereditary colorectal cancer. However, review of hereditary colorectal cancer case reports reveals occasional description of CALS on physical exam. METHODS: We describe the colonic and extracolonic phenotype in a family with CALS and early onset colorectal neoplasia (adenomas and/or cancer) and review 23 additional families reported in the literature. RESULTS: Among the 24 families, 32/59 (54.2%) individuals had colorectal adenomas diagnosed at a mean age of 15.7 +/- 1.1 (SE) years (range 5-38 years). The majority (24/32, 75.0%) of persons at first colorectal examination had oligopolyposis (< 100 polyps) versus polyposis (> or = 100 polyps). Forty-two of 59 (71.2%) individuals were affected with colorectal cancer, diagnosed at a mean age of 31.9 +/- 2.7 years (range 5-70 years). A brain tumor was found in 28/59 (47.5%) affected individuals (4 families with 2 or more cases) with an overall mean age of diagnosis of 16.5 +/- 1.2. Lymphoma and/or leukemia was found in 8/24 (33.3%) families (one family with 3 cases). Two families had mutation of the mismatch repair gene, hPMS2 (1 with homozygous germline mutation), while two carried homozygous germline mutations of another mismatch repair gene, hMLH1. CONCLUSIONS: Café-au-lait spots with early onset colorectal neoplasia may identify families with a variant of HNPCC characterized by oligopolyposis, glioblastoma at young age, and lymphoma. This variant may be caused by homozygous mutation of the mismatch repair genes, such as hPMS2 or hMLH1.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/complicaciones , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/patología , Adolescente , Adulto , Edad de Inicio , Anciano , Disparidad de Par Base , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Manchas Café con Leche , Niño , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación del ADN , Femenino , Glioblastoma/genética , Glioblastoma/patología , Humanos , Linfoma/genética , Linfoma/patología , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
Colorectal cancer is the second leading cause of cancer death, after lung cancer, in the USA. The great majority (80%) of patients with colorectal cancer have sporadic disease with no evidence of having inherited the disorder. In the remaining 20%, a potentially definable genetic component exists. With the discovery of gene mutations related to hereditary colorectal cancer, risk assessment based on genetic test results is now feasible. The following review focuses on the two well-described colorectal cancer genetic syndromes-familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, the process of genetic counselling, currently available genetic tests, and indications for their use.
Asunto(s)
Poliposis Adenomatosa del Colon/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Asesoramiento Genético/métodos , Pruebas Genéticas/métodos , Poliposis Adenomatosa del Colon/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Predisposición Genética a la Enfermedad , Humanos , MutaciónRESUMEN
The risk of periampullary cancer in patients with classic familial adenomatous polyposis (FAP) is significantly increased compared with the general population. However, the incidence of this extracolonic manifestation in attenuated FAP (AFAP) is unknown. We report the case of a 38 year old woman with no known family history of polyposis or colorectal cancer, who presented with ampullary adenocarcinoma. Diagnosis of AFAP was made only after evaluation of the patient's extended family history and genetic testing. This case report suggests that AFAP should be included in the differential diagnosis of patients with ampullary/duodenal tumours.