Turcot syndrome is a rare, inherited condition characterized by the development of numerous precancerous growths (adenomatous polyps) in the colon and rectum, alongside primary tumors in the brain or spinal cord. This genetic disorder is uncommon, with about 150 to 170 cases reported. Its distinct feature is the presence of both gastrointestinal and central nervous system manifestations.
Genetic Causes and Subtypes
Turcot syndrome stems from mutations in different genes. The two primary genetic pathways involve either the APC gene or a group of mismatch repair (MMR) genes. When mutations occur in the APC gene, the syndrome is linked to familial adenomatous polyposis (FAP), a condition known for developing thousands of polyps in the colon. In contrast, mutations in MMR genes such as MLH1, MSH2, MSH6, or PMS2 are associated with Lynch syndrome (hereditary non-polyposis colorectal cancer, or HNPCC).
The specific gene mutation influences the type of brain tumor that develops. Individuals with APC gene mutations commonly develop medulloblastomas, malignant tumors found in the cerebellum that often manifest in childhood. Conversely, mutations in the MMR genes are associated with gliomas, particularly glioblastoma multiforme, a more aggressive brain tumor. Turcot syndrome is categorized into Type 1 (MMR gene mutations and Lynch syndrome) and Type 2 (APC gene mutations and FAP).
Associated Cancers and Symptoms
The syndrome involves the development of numerous adenomatous polyps throughout the colon and rectum, which carry a high risk of transforming into colorectal cancer. These polyps can appear at an early age, sometimes numbering in the thousands. If left untreated, nearly all individuals with APC gene mutations will develop colorectal cancer by age 50. Symptoms can include rectal bleeding, changes in bowel habits (diarrhea or constipation), abdominal pain, and unexplained weight loss.
Central nervous system tumors accompany the gastrointestinal manifestations. Medulloblastomas, common in those with APC gene mutations, cause symptoms such as headaches, nausea, vomiting, and balance problems due to increased pressure within the skull. Glioblastomas, linked to MMR gene mutations, can also cause neurological symptoms depending on their size and location, including vision problems, seizures, or weakness in a limb. Less common manifestations include skin abnormalities like café-au-lait spots, benign fatty tumors (lipomas), or epidermal cysts.
Diagnosis and Screening Protocols
Diagnosis of Turcot syndrome is suspected based on a person’s clinical presentation, particularly the co-occurrence of colorectal polyps or cancer and a primary brain tumor, along with a family history. A colonoscopy is performed to visualize the colon and rectum, identify and evaluate polyps, and take biopsies for cancerous changes.
Brain imaging techniques, such as magnetic resonance imaging (MRI) or computed tomography (CT) scans, detect and characterize central nervous system tumors, providing information on their size, location, and type. The definitive diagnosis relies on molecular genetic testing, which identifies specific mutations in the APC or MMR genes. Following a confirmed diagnosis, regular screening protocols are established for affected individuals and at-risk family members. This includes frequent colonoscopies, potentially starting as early as age 10-12 for those with APC mutations, and regular neurological evaluations to monitor for brain tumor development.
Management and Treatment Approaches
Managing Turcot syndrome requires an individualized approach, addressing both gastrointestinal and neurological aspects. For gastrointestinal issues, surveillance through regular colonoscopies detects and removes polyps before they become cancerous. In many cases, a prophylactic colectomy (surgical removal of part or all of the colon) is recommended to significantly reduce colorectal cancer risk, especially when numerous polyps are present.
Treatment for brain tumors depends on several factors, including the tumor’s type, size, and location. Surgical removal is often the initial step, aiming to remove as much of the growth as safely possible while preserving surrounding healthy tissue. This may be followed by radiation therapy or chemotherapy, tailored to individual tumor characteristics. A multidisciplinary healthcare team, including gastroenterologists, neuro-oncologists, surgeons, genetic counselors, and other specialists, provides coordinated care and support.