Turcot syndrome
Turcot syndrome is a rare genetic disorder defined by the occurrence of primary brain tumors and multiple colorectal adenomas. It is characterized by adenomatous polyps in the gastrointestinal tract and central nervous system tumors, specifically medulloblastoma and glioma. The syndrome has two types: Type 1, associated with Lynch syndrome and characterized by numerous large colonic polyps, and Type 2, linked to familial adenomatous polyposis (FAP) with smaller polyps. The genetic mutations involved include alterations in the adenomatous polyposis coli (APC) gene and mismatch repair genes like MLH1 and PMS2.
Symptoms often include gastrointestinal issues such as diarrhea and abdominal pain, as well as neurological symptoms resulting from brain tumors. Diagnosis typically involves identifying polyp formations and genetic testing for mutations. Treatment may involve surgical removal of tumors and polyps, although complete removal can be challenging. While the prognosis is generally poor due to the malignancy of polyps at diagnosis, early detection and advances in genetic screening have improved outcomes for some patients. An interdisciplinary approach to treatment enhances care for those affected by Turcot syndrome.
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Subject Terms
Turcot syndrome
ALSO KNOWN AS: Brain tumor-polyposis syndrome, glioma-polyposis syndrome
RELATED CONDITIONS: Malignant tumors of the central nervous system (CNS), familial polyposis of the colon, familial adenomatous polyposis (FAP), Gardner syndrome, Lynch syndrome
DEFINITION: Turcot syndrome is a rare genetic disorder clinically characterized by the concurrence of a primary brain tumor and multiple colorectal adenomas. This syndrome is characterized by adenomatous polyps (benign growths) in the mucous lining of the gastrointestinal tract and tumors of the central nervous system, including medulloblastoma and glioma. It was first reported by Canadian surgeon Jacques Turcot in 1959.
Risk factors: Turcot syndrome has been linked to various mutations in several genes. Type 1 Turcot syndrome seems to be inherited in an autosomal recessive manner, while type 2 appears to be autosomal dominant. Mutation or mismatch of the adenomatous polyposis coli (APC) gene in chromosome 5q is most likely involved in the disease. Mismatch repair genes, such as MLH1 or PMS2, are found in some families. The types of brain tumors differ, depending on the type of mutation. APC mutations are more commonly associated with medulloblastoma, while mismatch repair genes are associated with glioblastoma. The gene map locus is 7p22, 5q21–q22, or 3p22.3.
Etiology and the disease process: Turcot syndrome manifests as a clinical variant of familial adenomatous polyposis (FAP) or of Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC). The exact cause of Turcot syndrome is not known, but it is directly related to gene mutations.
In this syndrome, there are two types of polyposis coli in combination with central nervous system tumors. Type 1, the LS variant, is characterized by multiple colonic polyps numbering up to one hundred; some may exceed 3 centimeters (cm) in diameter. These polyps frequently undergo malignant transformation in the second and third decades of life. A familial cluster has been described in several of the type 1 cases. In type 2, numerous small colonic polyps are present, and the mode of inheritance may be autosomal dominant concerning colonic lesions.
Turcot syndrome may be divided into two distinct entities. One type is associated with gliomas and LS, characterized by germ-line mutations in the mismatch repair genes MLH1 and PMS2. The second entity includes patients who develop a central nervous system tumor (FAP cases). These patients carry germ-line mutations in the APC gene, indicating a predisposition to brain tumors.
Incidence: Turcot syndrome is rare with only between 150 and 170 cases recorded, and it is strongly associated with an underlying genetic cause. The most common brain tumors associated with Turcot syndrome are medulloblastoma and glioblastoma multiforme. The glioblastomas and colorectal tumors often have replication errors that are characteristic of LS. APC gene–associated colon cancer typically occurs between ages twenty and forty, while LS-associated colon cancer generally arises between forty and sixty.
Symptoms: The symptoms of Turcot syndrome are associated with polyp formation, and they include diarrhea, bleeding from the rectum, fatigue, abdominal pain, and weight loss. Because of the development of brain tumors, patients with this disease may also experience neurological symptoms, depending on the type, size, and location of the tumors. Patients with Turcot syndrome commonly complain of skin abnormalities, including café-au-lait spots, multiple lipomas (fatty tumors), and multiple scalp basal cell carcinomas (skin cancers of the scalp). Turcot syndrome polyps may be somewhat fewer than in FAP, but they tend to be larger (greater than 3 cm in diameter). Many patients with Turcot syndrome have APC gene mutations, pigmented ocular fundus lesions, epidermal inclusion cysts, or osteosclerotic jaw lesions consistent with Gardner syndrome.
Screening and diagnosis: Patients with Turcot syndrome often have multiple adenomatous colon polyps or colorectal cancer, along with glioblastoma or medulloblastoma. Generally, blood tests can confirm a mutation in the APC gene, the PMS2 gene, or the MLH1 gene. If a specific gene mutation is found, family members are also tested for Turcot syndrome.
Treatment and therapy: Typically, tumors, such as adenomatous sigmoid polyps, are removed. Brain tumors, depending on their location, are more difficult to remove surgically. Colectomy and gastrectomy are also common treatments for patients with Turcot syndrome. As advances, such as targeted therapies, are made in the realm of general cancer treatment, patients with Turcot syndrome have benefitted.
Prognosis, prevention, and outcomes: In most cases, a complete of the brain tumors is difficult, and the colonic polyps are malignant at the time of diagnosis, resulting in poor prognosis. A better prognosis can be expected with early diagnosis, and this has become more of a reality with advances in screening tests and genetic testing. A shift to a more interdisciplinary approach has also aided Turcot syndrome patients, as gastrointestinal and neurological doctors can increasingly work together on an integrative treatment approach.
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