Turcot syndrome (TS), also known as brain tumor-polyposis syndrome (BTPS) was initially described in 1959 by Turcot [1] [2] [3]. It is characterized by central nervous system tumors like glioblastoma and medulloblastoma with colorectal polyps and adenocarcinoma of the colon. The syndrome is classified into two types [4] [5]:

• TS or BTPS Type I: characterized by glioblastoma, relatively few colorectal polyps, and genetic defects which are present in hereditary nonpolyposis colon cancer (HNPCC). It is inherited in an autosomal recessive pattern. The risk of colorectal cancer in these patients is greater than 50%. Although parents of affected individuals may be asymptomatic, their siblings may suffer from the same condition.

• TS or BTPS Type II: characterized by genetic defects which are present in familial adenomatous polyposis (FAP), numerous (hundreds or more than thousand) colorectal polyps, and a high risk of arising of medulloblastoma. This type is frequently inherited in an autosomal dominant pattern and affects several generations of the same family.

Not all patients can be classified simply into one of these two types [6] [7]. The occurrence of synchronous tumors has been associated with a poor prognosis [8].

Patients present in their teens with nonspecific symptoms and signs. Gastrointestinal manifestations like diarrhea, rectal bleeding, and abdominal pain occur in patients with colorectal polyps or colon cancer, while headache, vomiting, and seizures are the clinical features of patients with brain tumors.

Affected individuals may also develop other conditions such as malignant tumors of the thyroid or adrenal gland, basal cell carcinomas, cafe-au-lait spots, and lipomas [4] [9].

• Familial Adenomatous Polyposis

  Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. [ncbi.nlm.nih.gov]

  Risk Analysis for Brain Tumors in Familial Adenomatous Polyposis. [nejm.org]

  adenomatous polyposis coli, and hereditary nonpolyposis colorectal cancer. [medlink.com]

• Fatigue

  Página 48 - Our neighbours, the Indian and Mulatto inhabitants of the open palmthatched huts, as we returned home fatigued with our ramble, were either asleep in their hammocks or seated on mats in the shade, too languid even to talk. ‎ [books.google.es]

  The disorder may either be inherited in an autosomal recessive or autosomal dominant manner The symptoms of the condition may include formation of benign liver nodules, anemia, diarrhea, rectal bleeding, and fatigue. [dovemed.com]

  Symptoms associated with polyp formation may include diarrhea, bleeding from the end portion of the large intestine (rectum), fatigue, abdominal pain, and weight loss. [rarediseases.org]

• Diarrhea

  Symptoms include: Diarrhea Abdominal pain Weight loss Cognitive difficulties as a result of the central nervous system effects Behavioral changes caused by brain tumors There are about fewer than 2,000 people with the condition in the United States. [medexsupply.com]

  These growths are associated with bleeding from the rectum, diarrhea, constipation, abdominal pain, and/or weight loss. The number and size of these polyps may vary greatly from case to case, ranging from fewer than 10 to more than 100. [thinkgenetic.com]

  The disorder may either be inherited in an autosomal recessive or autosomal dominant manner The symptoms of the condition may include formation of benign liver nodules, anemia, diarrhea, rectal bleeding, and fatigue. [dovemed.com]

  Other included symptoms are related to GI tract syndromes, including Diarrhea, Bleeding from rectum (the terminal portion of the large intestine) Exhaustion and tiredness Abdominal spasm Unexplained weight loss Apart from GI tract related syndrome, individuals [syndromespedia.com]

  Symptoms associated with polyp formation may include diarrhea, bleeding from the end portion of the large intestine (rectum), fatigue, abdominal pain, and weight loss. [rarediseases.org]

• Abdominal Pain

  These growths are associated with bleeding from the rectum, diarrhea, constipation, abdominal pain, and/or weight loss. The number and size of these polyps may vary greatly from case to case, ranging from fewer than 10 to more than 100. [thinkgenetic.com]

  Symptoms include: Diarrhea Abdominal pain Weight loss Cognitive difficulties as a result of the central nervous system effects Behavioral changes caused by brain tumors There are about fewer than 2,000 people with the condition in the United States. [medexsupply.com]

  Patients who develop colon cancer can have symptoms such as abdominal pain, a change in stool habits, or the presence of blood in the stool. [wisegeek.com]

  Symptoms associated with polyp formation may include diarrhea, bleeding from the end portion of the large intestine (rectum), fatigue, abdominal pain, and weight loss. [rarediseases.org]

• Nausea

  A previously healthy 9-year-old girl presented with ataxia, headaches, and nausea of 1 month's duration. Magnetic resonance imaging demonstrated a large posterior fossa mass. [ncbi.nlm.nih.gov]

  Symptoms & Signs Some symptoms of the syndrome include headache, vomiting, nausea, personality & behavior changes, mood swings, loss of memory, seizures, reduced alertness, vision problems, hearing loss, decreased sensation of a body area, lethargy, general [signssymptoms.org]

  […] deficit hyperactivity disorder (50%) Hypertonia- increase in muscle tension and a reduced ability of a muscle to stretch (50%) Increased intracranial pressure- pressure inside of the skull (50%) Migraine (50%) Muscular hypotonia-low muscle tone (50%) Nausea [thinkgenetic.com]

  J AAPOS. 2014; 18(2):186-8 [ PubMed ] Related Publications A previously healthy 9-year-old girl presented with ataxia, headaches, and nausea of 1 month's duration. Magnetic resonance imaging demonstrated a large posterior fossa mass. [cancer-genetics.org]

  Symptoms include diarrhea, weight loss, nausea,vomiting, and anorexia, as well as paresthesias,seizures, and tetany related to electrolyteabnormalities. [slideshare.net]

• Gagging

  A missense mutation (GAG to AAG) at codon 705 of hPMS2 gene was detected in one allele of this patient, which was inherited from his mother without tumors. [ncbi.nlm.nih.gov]

• Hematochezia

  A 67-year-old woman presented with hematochezia and an episode of transient expressive dysphasia. She was found to have multiple colonic polyps with adenocarcinomatous changes. [ncbi.nlm.nih.gov]

• Flexion Contracture

  contracture- inability to fully straighten joing (7.5%) Gait (walking) disturbance (7.5%) Hallucinations (7.5%) Hemiplegia/hemiparesis- weakness of one side of the body (7.5%) Intestinal polyposis (7.5%) Memory impairment (7.5%) Neoplasm of the liver [thinkgenetic.com]

• Cafe-Au-Lait Spots

  Cell 126:297–308 PubMed CrossRef Google Scholar Korf BR (1992) Diagnostic outcome in children with multiple cafe au lait spots. [doi.org]

  Additional non-cancerous symptoms associated with Turcot syndrome include small, coffee-colored spots on the skin (cafe-au-lait spots), the formation of multiple, benign fatty tumors (lipomas), and/or the development of a type of skin cancer known as [thinkgenetic.com]

  […] corpus callosum 0001274 Percent of people who have these symptoms is not available through HPO Abnormality of abdomen morphology 0001438 Astrocytoma 0009592 Autosomal recessive inheritance 0000007 Axillary freckling 0000997 Basal cell carcinoma 0002671 Cafe-au-lait [rarediseases.info.nih.gov]

  The occurrence of colorectal cancer occurs later in TS2 than in TS1, and the skin lesions look more like epidermal cysts[10] rather than cafe au lait spots if present at all. [statpearls.com]

  She also had multiple cafe-au-lait spots. [genome.jp]

• Axillary Freckling

  Both children had features of neurofibromatosis type 1 including atypical café au lait spots and axillary freckling without a family history consistent with neurofibromatosis type 1, familial adenomatous polyposis, or hereditary nonpolyposis colorectal [ncbi.nlm.nih.gov]

  freckling, and hyperpigmented spots. [hindawi.com]

  freckling 0000997 Basal cell carcinoma 0002671 Cafe-au-lait spot 0000957 Ependymoma 0002888 Glioblastoma multiforme 0012174 Hypermelanotic macule Hyperpigmented spots 0001034 Leukemia 0001909 Lymphoma Cancer of lymphatic system 0002665 Medulloblastoma [rarediseases.info.nih.gov]

  However, eight café au lait macules (0.8-1 cm in size) with irregular borders and a few small ( 5 mm) axillary freckles were noted on examination. There were no neurofibromas and no Lisch nodules were seen on ophthalmic examination. [clincancerres.aacrjournals.org]

• Loss of Attention

  Abdominal pain (90%) Constipation (90%) Gastrointestinal hemorrhage (bleeding) (90%) Glioma- type of brain tumor (90%) Malabsorption- inability to absorb nutrients (90%) Neoplasm (benign or cancerous growth) of the colon (90%) Weight loss (90%) Attention [thinkgenetic.com]

• Hyperactivity

  […] pain (90%) Constipation (90%) Gastrointestinal hemorrhage (bleeding) (90%) Glioma- type of brain tumor (90%) Malabsorption- inability to absorb nutrients (90%) Neoplasm (benign or cancerous growth) of the colon (90%) Weight loss (90%) Attention deficit hyperactivity [thinkgenetic.com]

• Hyperreflexia

  […] stretch (50%) Increased intracranial pressure- pressure inside of the skull (50%) Migraine (50%) Muscular hypotonia-low muscle tone (50%) Nausea and vomiting (50%) Neoplasm of the rectum (50%) Seizures (50%) Abnormal pyramidal signs- plantar extension and hyperreflexia [thinkgenetic.com]

• Onset in Adolescence

  A polyposis genetic disorder with an onset in adolescence presenting with gastrointestinal multiple colorectal adenomas and primary central nervous system (CNS) tumors (eg, supratentorial glioblastoma and cerebellar medulloblastoma). [accessanesthesiology.mhmedical.com]

Workup of a patient suspected with TS consists of a thorough patient and family history, a clinical examination, and a battery of tests. A family history of the condition provides the initial clue to diagnosis. Sigmoidoscopy and colonoscopy form the mainstay for confirming the diagnosis followed by histological evaluation of the biopsy specimen. Computed tomography (CT) and magnetic resonance imaging (MRI) studies are necessary to detect brain tumors [10]. Histology of the tumors found in TS has features similar as in the same tumors found in patients without TS [9] [11] [12].

If a parent is known to suffer from TS, then it is recommended that his/her children are screened at regular intervals with a sigmoidoscopy until the age of 40 years to exclude colorectal polyps and an arising of malignancy [13]. Genetic testing is also recommended and if mutations are present it should be followed by genetic counseling.

• Multiple Colonic Polyps

  She was found to have multiple colonic polyps with adenocarcinomatous changes. Computed tomography brain scan and computed tomography-guided biopsy revealed a left frontoparietal glioblastoma multiforme. [ncbi.nlm.nih.gov]

  Turcot syndrome Oncology A syndrome characterized by multiple colon polyps and brain tumors–eg, ependymoma, glioblastoma, medulloblastoma Turcot, Jacques, Canadian surgeon, 1914–. [medical-dictionary.thefreedictionary.com]

  It is characterized by multiple colonic polyps and an increased risk of colon and primary brain cancers. Epidemiology Turcot syndrome is a rare disease. Patients typically present in the second decade 3. [radiopaedia.org]

  Turcot syndrome is diagnosed based on the symptoms in a person with known multiple colonic polyps who develops a primary brain tumour with a relevant family history. [contact.org.uk]

• Polyps

  Moreover, 45% of the total polyps and all polyps with a diameter exceeding 2 cm showed malignant transformation, indicating the precancerous nature of these polyps. [ncbi.nlm.nih.gov]

  Group II: Comprises patients with small polyps numbering fewer than 10, whereas Group III: Comprises patients with innumerable small polyps, usually more than 100. [accessanesthesiology.mhmedical.com]

The patient was diagnosed as having Turcot syndrome, and was then transferred to the Department of Surgery for treatment of an obstruction in the sigmoid colon and small intestinal invagination. [ncbi.nlm.nih.gov]

The treatment of brain tumor is specific, like site, size and type of brain tumor. [syndromespedia.com]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

In the event of tumor development, surgical resection is the mainstay treatment. [statpearls.com]

Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Please see also our disclaimer. This site complies with the HONcode standard for health information: verify here. Database updated 2019-02-19. [diseasesdatabase.com]

Much of the information about the prognosis of TS has been gained from analyses of reported cases. [statpearls.com]

What is the Prognosis of Turcot Syndrome? (Outcomes/Resolutions) The prognosis of Turcot Syndrome depends on the severity of the symptoms, the overall health status of the affected individual, and his/her response to treatment. [dovemed.com]

As he is the issue of a family with consanguinity (Figure 5), this enabled a precautionary management that improved patient and siblings prognosis. [hindawi.com]

In mismatch repair-deficient (dMMR) tumours, BRAF mutations are associated with a good prognosis, whereas in MMR-competent tumours, they are detrimental. [cancer-genetics.org]

• Prognosis in advanced cases is poor, and death is usually due to malignant brain tumor, but some patients die due to colorectal malignancy. • An understanding (and classification) of the disease at the genetic level is likely to lead to the most impactful [medlink.com]

Possible etiology and neurosurgical, clinically important characteristics of this rare syndrome, such as the young age of the patient and the relatively long survival time, will be discussed. [ncbi.nlm.nih.gov]

With further research into the etiology of this condition, scientists determined that the disease was not an independent and clearly-defined entity. Instead, it represented a subset of other syndromes putting patients at risk for different cancers. [wisegeek.com]

(Etiology) Turcot Syndrome is caused by mutation(s) in the APC, MLH1, or PMS2 genes. Based on the gene mutation causing the condition and the mode of inheritance, the disorder is classified into Type 1 and Type 2 types. [dovemed.com]

Cancer Res 55:5548–5550 PubMed Google Scholar Peltomaki P (2001) Deficient DNA mismatch repair: a common etiologic factor for colon cancer. [doi.org]

If a brain tumor arises in a patient with either HNPCC or FAP, then the patient is considered to have TS1 or TS2, respectively, although the association with either of these inherited mutations is not necessary.[2] Etiology The cause of Turcot syndrome [statpearls.com]

Epidemiology Turcot syndrome is a rare disease. Patients typically present in the second decade 3. [radiopaedia.org]

The New England journal of medicine. 1995 Mar 30 [PubMed PMID: 7661930] [3] Haggar FA,Boushey RP, Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. [statpearls.com]

To determine whether familial adenomatous polyposis predisposes patients to brain tumors, patients and their first-degree relatives enrolled in the Hopkins registry were compared with the general U.S. population, as represented in the surveillance, Epidemiology [nejm.org]

Epidemiology The incidence of familial polyposis of the colon is about 1 in 10,000 live births [ 1 ]. Colonic polyps begin developing at a mean age of 15 years [ 1 ]. [patient.info]

Approximately 75% to 80% of individuals with APC-associated polyposis conditions have an affected parent.[3] Pathophysiology Turcot syndrome can arise from mutations in the MMR genes (type I, associated with HNPCC) or the APC genes (type II, associated [statpearls.com]

Meyer Children's University Hospital, Florence, Italy Laura Giunti, Ugo Ricci, Sabrina Giglio, Elena Andreucci & Maurizio Genuardi Department of Pediatrics, University of Florence, Florence, Italy Valentina Cetica & Iacopo Sardi Department of Clinical Pathophysiology [nature.com]

The purpose of this article is to describe the pathophysiology, genetic testing, surveillance, surgical interventions, and psychosocial issues. The genetic defect in FAP is germline mutation in the adenomatous polyposis coli (APC) gene. [cancer-genetics.org]

Although its inheritance is unclear, hereditary and sporadic cases have been described in the literature. [15] Pathophysiology With the exception of Cronkhite-Canada Syndrome, all of the intestinal polyposis syndromes have been associated with genetic [emedicine.com]

The goal of screening in TS, whether genetic or clinical, would be to prevent complications of the disease. [statpearls.com]

At the present time, there are no methods or guidelines available for the prevention of Turcot Syndrome, since it is a highly uncommon genetic disorder. [dovemed.com]

Using mismatch repair corrects damage done to DNA to prevent a tumor from growing. Sometimes a mutation (change in DNA sequence) causes the parts of the mismatch repair system not to work, which means that it cannot fix other mutations. [thinkgenetic.com]

But some people with Lynch syndrome choose to have their colon removed to help prevent cancer from forming. Women who are finished having children may also have their uterus and ovaries removed. [webmd.com]

However, the number of polyps is so high that it is virtually impossible to prevent the colorectal cancer endoscopically and it is advisable to remove the whole large intestine surgically with formation of ileostomy or ileo-anal pouch. [health-tutor.com]

1. Turcot J, Despres JP, St Pierre F. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Diseases of the Colon and Rectum. 1959;2: 465–468.
2. Tops CMJ, Vasen HFA, van Berge Henegouwen G, et al. Genetic evidence that Turcot syndrome is not allelic to familial adenomatous polyposis. American Journal of Medical Genetics. 1992;43(5):888–893.
3. Mori T, Nagase H, Horii A, et al. Germ-line and somatic mutations of the APC gene in patients with Turcot syndrome and analysis of APC mutations in brain tumors. Genes Chromosomes and Cancer. 1994;9(3):168–172.
4. Paraf F, Jothy S, Van Meir EG. Brain tumor-polyposis syndrome: two genetic diseases? Journal of Clinical Oncology. 1997;15(7):2744–2758.
5. Paraf F. Turcot syndrome: evolution of knowledges. Gastroenterologie Clinique et Biologique. 1994; 18(3):297–299.
6. Chan TL, Yuen ST, Chung LP, et al. Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome. Genes Chromosomes Cancer. 1999;25(2):75–81.
7. Hamilton SR, Liu B, Parsons RE, et al.The molecular basis of Turcot’s syndrome. N Engl J Med.1995; 332(13):839-847.
8. Sabiq D, Al-Otaibi F, Alzahrani A, et al. Turcot Syndrome: A Synchronous Clinical Presentation of Glioblastoma Multiforme and Adenocarcinoma of the Colon. Case Reports in Oncological Medicine Volume 2012 (2012); Article ID 720273
9. Yan H, Giardiello F. Brain tumor-polyposis (BTP) syndrome in Russell and Rubinstein’s pathology of tumors of the nervous system. Hodder Arnold 2006;65b:1003-1010.
10. Ozerov SS, Zakharov IV, Talypov SR, et al. Turcot syndrome. A rare case and literature review. J. of Neurosurgery. 2013;77(3):49-53.
11. Perry A. Familial Tumor Syndromes in Practical Surgical Neuropathology: a diagnostic approach. Churchill Livingstone 2010; 20:427-453.
12. Rutz HP, Kikuchi T. The APC gene in Turcot’s syndrome. N Engl J Med.1995;333(8):524.
13. Pakakasama S, Tomlinson GE. Genetic predisposition and screening in pediatric cancer. Pediatr Clin North Am.2002;49(6):1393—1413.