Introduction
Turcot syndrome is a rare genetic disorder characterized by the coexistence of benign gastrointestinal growths and central nervous system tumors. Diarrhea, bleeding from the rectum (end portion of the large intestine), abdominal pain, fatigue, and weight loss are the possible symptoms of Turcot syndrome. Depending on the associated brain tumor type, location, and size, affected people may also experience neurological symptoms. Affected individuals may also have an increased risk of developing colorectal cancer.
What Is Turcot Syndrome?
Turcot syndrome (TS) is a rare, inherited condition where tumors develop in the brain, and abnormal growths of tissue (polyps) develop on the inner walls of the colon and rectum. This syndrome can be divided into two categories, each of which is brought on by a different gene mutation. The risk of brain cancer, particularly glioblastoma, and medulloblastoma, is higher in people with Turcot syndrome. The syndrome was first identified by Canadian surgeon Acques Turcot, who described it as colorectal cancer (CRC) with primary brain tumors. He noticed the syndrome in teenage siblings, who first developed a primary central nervous system (CNS) tumor after a few colonic polyps (a medulloblastoma and a pituitary adenoma, in his case).
Turcot syndrome is considered a variant of familial adenomatous polyposis (FAP), according to some researchers. Others consider it to be a distinct disorder. FAP is a condition that results in the formation of precancerous growths in the large intestine. Turcot syndrome occurs in some people due to a change (mutation) in the APC (adenomatous polyposis coli) gene. FAP can also be caused by APC gene mutations.
How Is Turcot Syndrome Classified?
Based on the gene mutations involved, Turcot syndrome is classified into two types.
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Type 1 - It is also known as true Turcot syndrome. Type 1 Turcot syndrome is inherited as an autosomal recessive trait. This indicates that Turcot syndrome-causing gene changes were passed down from both parents. The MLH1 and PMS2 gene alterations (mutations) are most likely to cause type 1 Turcot syndrome.
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Type 2 - Turcot syndrome type 2 is inherited as an autosomal dominant trait. In such cases, only one of the parents passes on the gene mutation that results in Turcot syndrome. An APC gene mutation causes type 2 Turcot syndrome. APC gene is involved in the prevention of tumor development and growth.
What Are the Causes of Turcot Syndrome?
Turcot syndrome has an unknown cause. However, the main etiology behind the incidence of Turcot syndrome is genetic mutations. Turcot syndrome is associated with a mutation in one or more genes. The APC gene is a tumor suppressor gene that is deleted in a biallelic, or homozygous fashion. The second cause of TS is homozygous mutations in the MMR genes or mismatch repair genes.
Turcot syndrome can be caused by mutations in the MMR genes (type I Turcot syndrome) or the APC genes (type II Turcot syndrome). Mutations in either gene can cause colorectal cancer and brain tumors, most commonly glioblastomas and medulloblastomas.
The deletion of a tumor suppressor gene causes normal colonic mucosa to transform into invasive carcinoma. Normal mucosa develops into polyps, which then progress into invasive cancer. Non-neoplastic hamartomas, hyperplastic mucosal proliferation, and adenomatous polyps are all examples of polyps. Colorectal cancers are typically caused by adenomatous polyps.
What Are the Symptoms of Turcot Syndrome?
Turcot syndrome is characterized by growths (polyps) in the intestine and one or more brain or spinal cord tumors. Symptoms associated with Turcot syndrome are mainly related to intestinal polyps and brain tumors. Turcot syndrome patients may develop multiple polyps from a young age.
Symptoms Related to Intestinal Polyps
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Constipation.
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Abdominal pain.
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Diarrhea.
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Weight loss.
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Rectal bleeding.
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Changes in bowel movements.
Symptoms of Brain Tumors
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Headaches.
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Seizures.
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Balance problems.
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Vomiting.
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Numbness in feet, hands, or limbs.
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Weakness.
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Double vision.
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Blurred vision.
What Are the Diagnostic Tests Used for Turcot Syndrome?
Several tests are used for the diagnosis of Turcot syndrome. It includes the following.
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Colonoscopy - It is used to view irregularities in the large intestine and rectum. Patients with evidence of APCor MMR (mismatch repair)gene mutations should routinely undergo early serial colonoscopies.
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Imaging - X-rays, MRIs (magnetic resonance imaging), and CT (computed tomography) scans are used to detect brain tumors, intestinal masses, and polyps. In some cases, your doctor may recommend a PET (positron emission tomography) scan.
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Biopsy - A biopsy will be performed to examine tissue samples from the colon or the brain.
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Sigmoidoscopy - It is used to evaluate the lower part of the intestine. Children and young adults who inherit a gene linked to Turcot syndrome may undergo regular sigmoidoscopy until age 35. These tests assist in the early detection and treatment of colon polyps.
How Is Turcot Syndrome Treated?
Treatment of Turcot syndrome is mainly based on clinical symptoms. Surgery is the mainstay of treatment for tumors. The only way to stop the growth of colorectal cancer in patients who have adenomatous, precancerous colorectal polyps is through total colectomy, especially if genetic confirmation is present. Surgical resection also applies to patients who develop brain tumors. Treatment options for TS patients include surgery, chemotherapy, and occasionally radiation therapy.
Inherited genetic mutations cannot be reversed using current technology. As a result, most Turcot syndrome treatment is defensive or preventative. It has been hypothesized that environmental factors may trigger mutations in additional loci in patients with HNPCC (hereditary nonpolyposis colorectal cancer) or FAP, leading to Turcot syndrome. The possible nature of these additional mutations or the environmental factors that might be responsible for them may be clarified in the future.
What Is the Differential Diagnosis of Turcot Syndrome?
Turcot syndrome can first manifest as polyposis of the colon or a primary brain tumor, so the differential list is based on which first appears. Early-onset hereditary nonpolyposis colorectal cancer may be associated with fewer precancerous polyps (HNPCC). Familial adenomatous polyposis is one type of polyposis of the colon. Cafe au lait spots, which resemble neurofibromatosis syndromes, can occasionally be a symptom of APC gene mutations. Patients may continue to experience tumor growth, particularly hematologic malignancies, which could be classified as constitutional mismatch repair deficiency syndrome if they also have colorectal cancer and a brain tumor.
Conclusion
Turcot syndrome is extremely uncommon. This genetic condition is characterized by the presence of multiple intestinal growths and brain tumors. Turcot syndrome patients have an increased risk of developing colorectal cancers. Clinical symptoms of Turcot syndrome are related to polyps (intestinal growths) and brain tumors. Only 150 cases of the condition have been reported in medical journals, but experts are unsure of the exact number. Treatment includes surgical management of abnormal growths and lifelong surveillance for complications.
