Polypose recto-colique familiale
480662
22189960
2007-10-25T19:18:59Z
Thijs!bot
105469
robot Ajoute: [[nl:Familiaire adenomateuze polypose]]
{{Voir homonymes|Polypose}}
{{CIM-10||ICD10=C18, D12}}
La '''Polypose recto-colique familiale''' est une maladie héréditaire à transmission autosomique dominante, prédisposant au [[cancer du côlon]]. Des centaines voir des milliers de polype colique apparaissent vers l'âge de 16 ans en moyenne (fourchette de valeurs 7-36 ans) qui en l'absence de colectomie (ablation du colon) dégénèrent systématiquement en cancer qui apparaissent vers l'âge de 39 ans (fourchette de valeurs 34-43 ans). Les signes extra coliques comprennent des polypes de l'[[estomac]], des [[ostéome]]s, des anomalies des dents, une hypertrophie de l'[[épithélium]] de la [[rétine]], des tumeurs des muscles, et d'autres cancers.
Les formes atténuées de la polypose adénomateuse familiale se manifestent par une augmentation significative du risque de cancer du colon mais avec beaucoup moins de polype (en moyenne 30) et localisés dans le colon proximal. Le risque de dégénérescence est plus tardive. La prise en charge de cette pathologie est différente.
Seul le traitement radical (colo-proctectomie) est envisageable.
== Autres noms ==
*Polypose adénomateuse autosomique dominante, forme familiale
*Polypose adénomateuse familiale
*Polypose intestinale familiale
== Pathologies intestinales par mutation du gène APC (Lésions associées) ==
Les '''pathologies intestinales par mutation du gène APC''' comprennent les pathologies suivantes dont les distinctions sont floues : la ''polypose recto-colique familiale'', les formes atténuées de la polypose recto-colique familiale, le ''syndrome de Gardner'' et le ''syndrome de Turcot''.
* [[syndrome de Gardner]] : tumeurs d'autres tissus : ostéome, fibrome, lipome, tumeur de la thyroïde ou des surrénales
* [[syndrome de Turcot]] : tumeur du système nerveux central : astrocytome, glioblastome, médulloblastome
==Signes et symptômes==
<!--
From the age of 16 onward, patients develop hundreds to thousands of polyps. These may bleed, leading to admixture of blood in the stool. If the blood is not visible, it is still possible for the patient to develop [[anemia]] due to gradually developing iron deficiency. If malignancy develops, this may present with [[weight loss]], altered bowel habit, or even with [[metastasis]] in the [[liver]] or elsewhere.
The genetic determinant in familial polyposis may also predispose carriers to other malignancies, e.g. of the [[duodenum]] and [[stomach]]. Other signs that may point at FAP are pigmented lesions of the [[retina]] ("congenital hypertrophy of the retinal pigment"), jaw cysts, [[sebaceous cyst]]s, and [[osteoma]]ta (benign bone tumors). The combination of polyposis, osteomas, [[fibroma]]s and sebaceous cysts is termed ''Gardner syndrome'' (with or without abnormal scarring).
-->
==Diagnostic et traitement==
<!--
In patients with a strong family of colorectal cancer and symptoms suggestive of polyposis, [[colonoscopy]] is indicated, with [[biopsy]] of a number of polyps (especially of those that appear [[dysplasia|dysplastic]]). In severe cases, a full or partial [[colectomy]] is required.
[[Blood test]]s ([[liver enzyme]]s) and [[medical ultrasonography|ultrasound]] of the abdomen are often performed to rule out [[metastasis]] to the liver.
[[Genetic testing]] provides the ultimate diagnosis in 95%; [[genetic counseling]] is usually needed in families where FAP has been diagnosed. Testing may also aid in the diagnosis of borderline cases in families that are otherwise known to have the FAP mutation.
-->
==Physio-pathologie==
<!--
FAP is due to mutations in the ''[[APC (gene)|APC]]'' gene, which is located on the fifth [[chromosome]] (5q21-q22), or in the ''[[MUTYH]]'' gene located on chromosome 1 (p34.3-p32.1).
''[[APC (gene)|APC]]'' is a [[tumour suppressor gene]], acting as a "gatekeeper" to prevent development of tumours. Mutation of ''APC'' also occurs commonly in incident cases of colorectal carcinoma, emphasizing its importance in this form of cancer.
Although the polyps are inherently benign, the first step of the [[Knudson hypothesis|two-hit hypothesis]] has already taken place: the inherited APC mutation. Often, the remaining "normal" [[allele]] is mutated or deleted, accelerating generation of polyps. Further mutations (e.g. in [[p53]] or ''KRAS'') to APC-mutated cells are much more likely to lead to cancer than they would in non-mutated [[epithelium|epithelial]] cells.
The normal function of the ''APC'' gene product is still being investigated; it is present both the [[cell nucleus]] and the membrane. The canonical tumor-suppressor function of Apc is suppression of the oncogenic protein beta-catenin. However, other tumor-suppressor functions of Apc may be related to cell adherence and [[cytoskeleton]] organization.
''[[MUTYH]]'' encodes [[DNA repair]] enzyme [[MYH glycosylase]]. During normal cellular activities, [[guanine]] sometimes becomes altered by [[oxygen]], which causes it to pair with [[adenine]] instead of [[cytosine]]. MYH glycosylase fixes these mistakes by [[base excision repair]], such that [[mutation]]s do not accumulate in the [[DNA]] and lead to tumor formation. When MYH glycosylase does not function correctly, DNA errors may accrue to initiate tumorigenesis with a clinical presentation similar to that in patients with Apc mutations.
-->
==Génétique==
<!--
Familial adenomatous polyposis can have different inheritance patterns and different genetic causes. When this condition results from mutations in the ''APC'' gene, it is inherited in an [[autosomal dominant]] pattern, which means one copy of the altered gene is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.
Mutations in the ''MUTYH'' gene are inherited in an [[autosomal recessive]] pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.
[[Prenatal testing]] is possible if a disease-causing mutation is identified in an affected family member; however, prenatal testing for typically adult-onset disorders is uncommon and requires careful [[genetic counseling]].
-->
<!--
==Animal Models==
The "ApcMin" mouse model was isolated in 1990 and harbors an Apc allele with a stop codon at position 850. Heterozygosity for this mutation results in a fully penetrant phenotype, with mice on a sensitive background developing over 100 tumors in the intestinal tract. Many other models have since appeared, including a model of attenuated FAP (the 1638N model) and several [[conditional mutants]] that allow for tissue-specific or temporal ablation of gene function.
In 2005, the "ApcPirc" rat model was isolated with a stop codon at position 1137. In constrast to the mouse models where >90% of tumors form in the small intestine, the Pirc rat forms tumors preferentially (>60%) in the large intestine, similar to the human clinical presentation. Genetic screens, pharmacological testing, and other areas of research have allowed for discoveries in the mouse and rat to be applied to the study of human FAP.
-->
==Épidémiologie==
<!--
The incidence of the mutation is between 1 in 10,000 and 1 in 15,000 births.
By age 35 years, 95% of individuals with FAP have polyps. Without colectomy, colon cancer is virtually inevitable. The mean age of colon cancer in untreated individuals is 39 years (range 34-43 years).
-->
==Traitement==
<!--
Treatment for FAP will require frequent surveillance [[colonoscopy]] investigations; in a number of cases, removal of the colon is necessary to prevent the development of malignancy, or to cure it. If a large part of the bowel is removed, construction of an [[ileostomy]] may be necessary.
Various medications are being investigated for slowing malignant degeneration of polyps, most prominently the [[non-steroidal anti-inflammatory drug]]s (NSAIDs).
-->
==Références==
* Gardner EJ. ''A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum.'' Am J Hum Genet 1951;3:167-76. PMID 14902760
* {{en}} Cindy Solomon, Randall W Burt, APC-Associated Polyposis Conditions In : GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2005. [http://www.genetests.org/query?dz=fap].
==Liens externes==
* {{OMIM|175100}}
{{Portail médecine}}
[[Catégorie:Maladie génétique de l'appareil digestif]]
[[Catégorie:Cancer héréditaire |Intestin]]
[[Catégorie:Tumeur de l'appareil digestif]]
[[de:Familiäre adenomatöse Polyposis]]
[[en:Familial adenomatous polyposis]]
[[ja:家族性大腸腺腫症]]
[[nl:Familiaire adenomateuze polypose]]
[[pl:Rodzinna polipowatość gruczolakowata]]
[[sk:Familiárna adenomatózna polypóza]]
[[ur:سلیلہ (مرض)]]