From the Guidelines
Gardner syndrome is caused by mutations in the APC gene located on chromosome 5q21-q22, which is inherited in an autosomal dominant pattern. This gene mutation leads to uncontrolled cell growth, resulting in polyps and tumors. The APC gene normally functions as a tumor suppressor by regulating cell growth and division 1. Gardner syndrome is characterized by multiple colorectal polyps, osteomas, dental abnormalities, and soft tissue tumors like epidermoid cysts.
Key Characteristics of Gardner Syndrome
- Multiple colorectal polyps with a high risk of becoming cancerous
- Osteomas (benign bone tumors)
- Dental abnormalities
- Soft tissue tumors like epidermoid cysts
- Inherited in an autosomal dominant pattern, meaning a person only needs to inherit one defective copy of the gene to develop the condition 1
Genetic Testing and Management
Genetic testing for APC mutations is recommended for diagnosis and for screening family members, as early detection allows for preventive measures 1. Management typically involves regular colonoscopies starting in adolescence, and many patients eventually require colectomy (surgical removal of the colon) to prevent colorectal cancer. Family members of affected individuals should undergo genetic counseling to understand their risk and appropriate screening protocols. Genetic testing can identify the disease-producing mutation in approximately 80% of kindreds, and once the mutation is found, other family members can be tested for the presence or absence of the same mutation with nearly 100% accuracy 1.
From the Research
Gene Mutation for Gardner Syndrome
- The gene mutation associated with Gardner syndrome is a mutation in the adenomatous polyposis coli (APC) gene, which is located on chromosome 5q21 2.
- This mutation can be inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to increase the risk of developing the condition 3.
- The APC gene mutation can lead to the development of various extracolonic manifestations, including osteomas, skin cysts, congenital hypertrophy of the retinal pigmented epithelium (CHRPE), and desmoid tumors (aggressive fibromatosis) 4, 5.
- A novel large deletion in the APC gene, known as EX10_16DEL, has been identified in a Chinese family with Gardner syndrome 4.
- Genetic testing and colonoscopy are recommended for adolescents and young adults with cranial osteomas, as they may be at risk of developing Gardner syndrome 6.
APC Gene Mutations
- Mutations in the APC gene can be somatic or germline, and can occur through various mechanisms, including point mutations, deletions, and insertions 2.
- The identification of APC gene mutations has significant implications for understanding the pathogenesis of colorectal neoplasia and for the diagnosis and counseling of individuals with inherited predispositions to colorectal cancer 2.
- The APC gene plays a critical role in the Wnt-signaling pathway, and mutations in this gene can lead to the accumulation of beta-catenin, which can contribute to the development of tumors 5.