Mismatch repair cancer syndrome

{{Short description|Cancer syndrome}} {{Infobox medical condition | synonyms = Brain tumor-polyposis syndrome, Glioma-polyposis syndrome, Turcot syndrome | name = Mismatch repair cancer syndrome | image = Autosomal recessive - en.svg | caption = This condition is inherited in an autosomal recessive manner | pronounce = | field = Oncology | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Mismatch repair cancer syndrome''' ('''MMRCS''') is a cancer syndrome associated with biallelic DNA mismatch repair mutations.<ref name="omim_276300">{{OMIM|276300}}</ref> It is also known as '''Turcot syndrome''' (after Jacques Turcot, who described the condition in 1959) and by several other names.<ref name="omim_276300" />

In MMRCS, neoplasia typically occurs in both the gut and the central nervous system (CNS).<ref name="omim_276300" /> In the large intestine, multiple colonic polyps develop; in the CNS, brain tumors. ==Genetics== Under the name '''constitutional mismatch repair-deficiency''' ('''CMMR-D'''), it has been mapped to MLH1, MSH2, MSH6 or PMS2.<ref name="pmid19293170">{{Cite journal |vauthors=Kratz CP, Holter S, Etzler J, Lauten M, Pollett A, Niemeyer CM, Gallinger S, Wimmer K |date=June 2009 |title=Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome |url=https://hal.archives-ouvertes.fr/hal-00552674/file/PEER_stage2_10.1136%252Fjmg.2008.064212.pdf |journal=Journal of Medical Genetics |volume=46 |issue=6 |pages=418–20 |doi=10.1136/jmg.2008.064212 |pmid=19293170 |s2cid=42347878}}</ref> Monoallelic mutations of these genes are observed in the condition known as Lynch syndrome or hereditary nonpolyposis colorectal cancer, while biallelic mutations are observed in CMMR-D.<ref name="pmid18709565">{{Cite journal |vauthors=Wimmer K, Etzler J |date=September 2008 |title=Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg? |journal=Human Genetics |volume=124 |issue=2 |pages=105–22 |doi=10.1007/s00439-008-0542-4 |pmid=18709565 |s2cid=32654505}}</ref> People expressing the HNPCC (which itself is considered autosomal dominant) trait are considered carriers of CMMR-D, thus CMMR-D is classified as autosomal recessive.{{citation needed|date=September 2020}}

The term "childhood cancer syndrome" has also been proposed.<ref name="pmid17851451">{{Cite journal |vauthors=Krüger S, Kinzel M, Walldorf C, Gottschling S, Bier A, Tinschert S, von Stackelberg A, Henn W, Görgens H, Boue S, Kölble K, Büttner R, Schackert HK |date=January 2008 |title=Homozygous PMS2 germline mutations in two families with early-onset haematological malignancy, brain tumours, HNPCC-associated tumours, and signs of neurofibromatosis type 1 |journal=European Journal of Human Genetics |volume=16 |issue=1 |pages=62–72 |doi=10.1038/sj.ejhg.5201923 |pmid=17851451 |doi-access=free}}</ref><ref name="pmid18376293">{{Cite journal |vauthors=Tan TY, Orme LM, Lynch E, Croxford MA, Dow C, Dewan PA, Lipton L |date=March 2008 |title=Biallelic PMS2 mutations and a distinctive childhood cancer syndrome |journal=Journal of Pediatric Hematology/Oncology |volume=30 |issue=3 |pages=254–7 |doi=10.1097/MPH.0b013e318161aa20 |pmid=18376293}}</ref> Café-au-lait macules have been observed.<ref name="pmid18273873">{{Cite journal |vauthors=Jackson CC, Holter S, Pollett A, Clendenning M, Chou S, Senter L, Ramphal R, Gallinger S, Boycott K |date=June 2008 |title=Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2 |journal=Pediatric Blood & Cancer |volume=50 |issue=6 |pages=1268–70 |doi=10.1002/pbc.21514 |pmid=18273873 |s2cid=34238025}}</ref>

==Diagnosis== Childhood to early adult onset HNPCC + malignant gliomas.{{Clarify|date=March 2026}} The polyps developed tend to be larger, fewer, and progress to malignancy earlier than those seen in familial adenomatous polyposis,<ref name="omim_276300">{{OMIM|276300}}</ref> a clinically similar condition with different underlying mutations. Diagnostic testing consists of a blood sample being collected, and a genetic specialist compares two copies of a patient's gene to normal MMR genes. If there are differences in the genes, the specialists are able to further test and decide if the patient has the deficiency.<ref>{{Cite web |title=Constitutional Mismatch Repair Deficiency Syndrome |url=https://www.stjude.org/disease/constitutional-mismatch-repair-deficiency.html |access-date=2020-03-10 |website=www.stjude.org |language=en}}</ref> ==History== OMIM currently includes "Turcot syndrome" under "mismatch repair cancer syndrome". Turcot syndrome is the association between familial polyposis of the colon and brain tumors<ref>{{DorlandsDict|eight/000112462|Turcot syndrome}}</ref> like medulloblastoma or malignant glioma. It was first reported by Canadian surgeon Jacques Turcot (1914–1977 ) ''et al.'' in 1959 and hence carries the first author's name.<ref>{{Cite journal |vauthors=Turcot J, Despres JP, St Pierre F |year=1959 |title=Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases |journal=Diseases of the Colon and Rectum |volume=2 |pages=465–8 |doi=10.1007/bf02616938 |pmid=13839882 |s2cid=27477524}}</ref>

== See also == * Gardner syndrome

== References == {{Reflist}}

== External links == * {{RareDiseases|420|Turcot syndrome; CNS tumors with Familial polyposis of the colon}} {{Medical resources | DiseasesDB = 29793 | ICD10 = | ICD9 = | ICDO = | OMIM = 276300 | MedlinePlus = | eMedicineSubj = ped | eMedicineTopic = 828 | MeshID = C536928 | Orphanet = 252202 }}

Category:Hereditary cancers Category:Autosomal recessive disorders Category:Rare diseases Category:Syndromes with tumors Category:DNA replication and repair-deficiency disorders Category:Syndromes affecting the nervous system Category:Syndromes affecting the gastrointestinal tract