Also known as brain tumor-polyposis syndrome or Glioma-polyposis syndrome
Associated with colonic adenomatous polyps, and a high incidence of brain tumors either medulloblastoma or glioblastoma multiforme.
If the PMS2 gene mutation is inherited from both parents and the condition is called Turcot syndrome or Constitutional MMR Deficiency.
Inheritance of Turcot syndrome can be dominant or recessive.
Recessive inheritance of Turcot syndrome is caused by compound heterozygous mutations in PMS2.
Homozygous or compound heterozygous mutation carriers had gastrointestinal cancer or adenomas as the first manifestation of CMMR-D.
A rare inherited disorder characterized by the association of benign (
adenomatous polyps in the mucous lining of the gastrointestinal tract with tumors of the central nervous system.
Polyp formation symptoms may include diarrhea, GI bleeding, fatigue, abdominal pain, and weight loss.
Any neurological symptoms, depends upon the type, size and location of the associated brain tumor.
The number and size of adenomatous polyps may vary greatly from case to case, ranging from fewer than 10 to more than 100.
Turcot syndrome may be divided into two forms:
type 1 is characterized by the presence of fewer than 100 colonic polyps.
These polyps are large in size and more likely to become malignant
Type 2 is characterized by smaller, more numerous colonic polyps, resembling familial adenomatous polyposis.
In cases of Turcot syndrome, the brain tumor is often a glioma, but other brain tumors that have been associated and include medulloblastomas, glioblastomas, ependymomas, and astrocytomas.
Medulloblastomas occur with greater frequency in the type 2 form of Turcot syndrome.
With Turcot syndrome there is a greater risk than the general population of developing colon cancer later in life.
Affected individuals have a predisposition to develop malignant tumors in the thyroid, adrenal, and/or abdominal tumors.
Advanced disease is manifests as dyskinesias, impaired cognition, hallucinations, apathy, sleepiness, autonomic dysfunction, dysphasia, dysarthria, posture and balance impairments, freezing of gait, recurrent falls, and disability requiring help for activities of daily living.
Additional findings associated with Turcot syndrome include: cafe-au-lait spots), the formation of multiple lipomas, and/or the development of skin basal cell carcinomas.
One type of Turcot syndrome is inherited as an autosomal recessive trait and the other as an autosomal dominant trait.
Turcot syndrome type 1, is
inherited as an autosomal recessive trait.
Mutations to two DNA mismatch repair genes-MLH1 and PMS2 may be responsible for development of this form of Turcot syndrome.
MLH1 is located on the short arm (p) of chromosome 3.
PMS2 is located on the short arm of chromosome 7 at band number 22.
The second type of Turcot syndrome, which is associated with familial adenomatous polyposis, is inherited as an autosomal dominant trait.
This form of Turcot syndrome results from mutations to the APC gene.
APC gene has been mapped to the long arm (q) of chromosome 5 (5q21-q22).
Evidence suggests that the APC gene functions as a tumor suppressor gene.
Mutations to the APC gene are associated with familial adenomatous polyposis and Gardner syndrome.
Turcot syndrome affects males and females in equal numbers.
Approximately 150 cases have been reported.
Symptoms of the following disorders can be similar to those of Turcot syndrome.
Familial adenomatous polyposis.
Gardner syndrome
Peutz-Jeghers syndrome
Cronkhite-Canada disease
Familial juvenile polyposis
A diagnosis is made based upon a detailed patient history, clinical evaluation, and a variety of specialized tests.
Children of an affected parent have a genetic risk of developing Turcot syndrome, regular colorectal screening is required until approximately age 35 to 40 to help ensure early detection and prompt, appropriate treatment.
DNA testing may detect family members who have inherited mutations of the APC gene or DNA mismatch repair genes to diagnosis the disorder before polyps develop.
Resection of the colon and rectum may prevent the risk of polyps develooong cancers.
With ileoproctostomy, rectal polyps may regress.
Patients with TS should also receive periodic neurological screenings to test for the presence of a brain tumor.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.