Detection of CHRPE is often the earliest clinical indicator for Gardner syndrome.Patients may be asymptomatic or may report cramping, diarrhea, rectal bleeding, constipation, and/or vomiting. Diagnosisĭiagnosis of Gardner syndrome is established through molecular genetic testing. Loss of function in the APC protein is thought to be the earliest event in the formation of adenomas. Mutations in the APC gene cause inactivation of the beta catenin protein resulting in the overactivation of proteins responsible for cell division. Beta catenin is responsible for regulating proteins that are responsible for stimulating cell division. The protein beta catenin is tightly regulated by the APC gene. APC protein is also important in mediating cell adhesion by helping regulate the manner of attachment of cells to other cells within the tissue. APC protein functions as a tumor suppressor gene and plays an important role in cell division, regulation and growth.
Disease severity and extracolonic findings are associated with the location of the APC mutation. The genetic material contained in the APC gene is used to transcribe the APC protein which is over 2800 amino acids in length. PathophysiologyĪPC gene is located on chromosome 5 and is genetically linked to band 5q21.
De novo mutations account for approximately 20% of individuals diagnosed with Gardner syndrome and have an absent family history of the disorder. Less commonly, with no known causes, Gardner syndrome can result from de novo mutations in the APC gene. Since Gardner syndrome is an autosomal dominant disorder, offspring of an affected parent pose a 50% chance of inheriting the disorder. However, ocular findings in Gardner Syndrome are often incidental so family history is the most important assessment of a patient's risk. The earliest and most common extra-colonic finding in Gardner syndrome is CHRPE and is found in nearly 90% of patients. Mutations of TP53 on chromosome 17, a deletion of the colon cancer gene (DCC) on chromosome 18, and loss of DNA methylation on chromosome 12 which causes a mutation of the RAS gene have all been linked as possible causes of Gardner syndrome. While Gardner syndrome is commonly recognized with mutations within the APC gene, there are other mutations that have been linked as possible causes of Gardner syndrome. APC gene is located on chromosome 5, within band 5q21, and encodes for a tumor suppressor gene. Gardner syndrome is an autosomal dominant disorder caused by germline mutations in the adenomatous polyposis coli (APC) gene. While the penetrance of the gene is nearly 100% in those affected with Gardner syndrome, there is variation in the expression both between and within affected families. In the United States, the prevalence of Gardner syndrome is 1 in 1,000,000 and has an incidence of 1 in 8,000. However, the absence of CHRPE cannot be considered a negative predictive indicator of Gardner syndrome. The presence of multiple and bilateral CHRPE is considered a clinical disease marker and is useful for early detection in individuals that are at risk. Gardner syndrome can also present with ocular manifestations that include the presence of multiple patches of congenital hypertrophy of the retinal pigment epithelium (CHRPE). However, Gardner syndrome has characteristic polyps in the colon and osteomas that help distinguish the disease from FAP. Both Gardner syndrome and FAP are characterized by the numerous adenomatous polyps lining the intestinal mucosal surface. Gardner syndrome is a rare phenotypic variant of familial adenomatous polyposis (FAP). 7.2.2 Characteristics of Gardner Syndrome related CHRPE.Optical coherence tomography (OCT) demonstrates a disruption of the highly-reflective signal from the ellipsoid zone in the region of the lesions, as indicated by the orange line on the scan. The lesions are flat, sharply circumscribed, placoid, chalky white, and lie at the level of the RPE. It is believed that these spots may develop secondary to deposition of an abnormal white material in retinal pigmented epithelial (RPE) cells rather than the usual darkly pigmented melanin. Groups of the spots, as seen here, are commonly referred to as "polar bear tracks" due to their color and resemblance of animal footprints. Grouped congenital albinotic spots of the retinal pigmented epithelium (polar bear tracks) Grouped congenital albinotic spots of the retinal pigmented epithelium (polar bear tracks) Category(ies): Retina, Vitreous Contributor: Jesse Vislisel, MD Photographer: Brice Critser, CRAĬongenital albinotic spots of the retinal pigmented epithelium (CASRPE) can be configured in solitary or grouped configurations.
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