Polypose family recto-colic

Other names

Polypose adénomateuse autosomic dominant, family form
Polypose adénomateuse family
Polypose intestinal family

Intestinal pathologies by change of gene APC (associated Lesions)

The intestinal pathologies by change of gene APC include/understand following pathologies whose distinctions are fuzzy: the polypose family recto-colic , attenuated forms of the polypose family recto-colic, the syndrome of Gardner and the syndrome of Turcot .

Syndrome of Gardner: tumors of other fabrics: ostéome, fibrome, lipome, tumor of thyroid or the suprarenals
Syndrome of Turcot: tumor of the central nervous system: astrocytome, glioblastome, médulloblastome

Signs and symptoms

Weakened due to gradually developing iron deficiency. Yew malignancy develops, this may present with Weight loss, altered bowel dress, gold even with Metastasis in the Liver gold elsewhere.

The genetic determining in family polyposis may also predisposes carriers to other malignancies, e.g off the Duodenum and Stomach. Other signs that may not At FAP are pigmented lesions off the Retina (" congenital hypertrophy off the retinal pigment"), jaw cysts, Sebaceous cyst S, and Osteoma your (benign bone tumors). The combination off polyposis, osteomas, Fibroma S and sebaceous cysts is termed Gardner syndrome (with gold without abnormal scarring). -->

Diagnosis and treatment

Biopsy off has number off polyps (especially off those that appear dysplastic). In severe boxes, full but partial Colectomy is required has.

Blood test S (Liver enzyme S) and ultrasound off 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 off borderline boxes in families that are otherwise known to cuts the FAP change. -->

Physiopathology

APC embarrassment, which is located one the fifth Chromosome (5q21-q22), but in the MUTYH embarrassment located one chromosome 1 (p34.3-p32.1).

APC has Tumor suppressor embarrassment, acting ace has " gatekeeper" to development prevent off tumors. Change off APC also occurs commonly in incident boxes off colorectal carcinoma, emphasizing its importance in this form off cancer.

Although the polyps are inherently benign, the first step off the two-hit hypothesis has already taken place: the inherited APC change. Often, the remaining " normal" Allele is mutated gold deleted, accelerating generation off polyps. Further changes (e.g in P53 gold KRAS ) to APC-mutated concealments are much more likely to lead to epithelial cancer than they would in non-mutated concealments.

Normal The function off the APC embarrassment product is still being investigated; it is present both the Concealment nucleus and the membrane. The canonical tumor-suppressor function off Apc is suppression off the oncogenic protein beta-catenin. However, other tumor-suppressor functions off Apc may Be related to concealment adherence and Cytoskeleton organization.

MUTYH encodes DNA to repair enzyme MYH glycosylase. Normal During cellular linen activities, Guanine sometimes becomes altered by even Oxygen, which causes it to with Adenine instead off Cytosine. Fixed MYH glycosylase thesis mistakes by Base excision to repair, such that Change S C not accumulate in the DNA and lead to tumor formation. When MYH glycosylase does not function correctly, DNA errors may increased to initiate tumorigenesis with has clinical presentation similar to that in patients with Apc changes. -->

Genetics

APC embarrassment, it is inherited in year Autosomal dominating pattern, which means one Copy off the altered embarrassment is sufficient to causes the disorder. In most boxes, year affected person has one relative with the condition.

Changes in the MUTYH recessive embarrassment are inherited in year Autosomal pattern, which means two copies off the embarrassment must Be altered for has person to Be affected by the disorder. Most often, the parents off has off child with year autosomal recessive disorder are not affected goal are carriers one Copy off the altered embarrassment.

Prenatal testing is possible yew has disease-causing change is identified in year affected family member; however, antenatal testing for typically adult-onset disorders is uncommon and requires careful Genetic counseling. --> Models animal The " ApcMin" foam model was isolated in 1990 and harbors year Apc allele with has stop codon At position 850. Heterozygosity for this change results in has fully penetrating phenotype, with mice one has sensitive background developing over 100 tumors in the intestinal leaflet. Many other models cuts since appeared, including has model off attenuated FAP (the 1638N model) and several temporal Conditional mutants that allow for tissue-specific but ablation off embarrassment function.

In 2005, the " ApcPirc" rat model was isolated with has stop codon At position 1137. In constrast to the foam models where >90% off tumors form in the small internal, the Pirc rat forms tumors preferentially (>60%) in the broad internal, similar to the human clinical presentation. Genetic screens, pharmacological testing, and other areas off research cuts allowed for discoveries in the foam and rat to Be applied to the study off human FAP. -->

Epidemiology

Treatment

Ileostomy may Be necessary.

Various medications are being investigated for slowing malignant degeneration off polyps, most prominently the Non-steroidal anti-inflammatory drug S (NSAIDs). -->

References

Gardner EJ. has off genetic and clinical study intestinal polyposis, has predisposing Factor for carcinoma off the colonist and rectum. Am J Hum Broom 1951; 3: 167-76. PMID 14902760
Cindy Solomon, Randall W Burt, APC-Associated Polyposis Conditions In: GeneReviews At GeneTests: Medical Genetics Information Resource (database online). Copyright, University off Washington, Seattle. 1997-2005.

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