Preferred Label : Mismatch repair cancer syndrome 1;
Symbol : MMRCS1;
CISMeF acronym : CMMRDS; MMRCS;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : Mmr deficiency; Turcot syndrome; BTPS1; Btp1 syndrome; CMMRDS; Brain tumor-polyposis syndrome 1; Constitutional mismatch repair deficiency syndrome; Mismatch repair deficiency; Childhood cancer syndrome;
Description : Constitutional mismatch repair deficiency is a rare childhood cancer syndrome with
4 main tumor types: hematologic malignancies, brain/central nervous system tumors,
colorectal tumors and multiple intestinal polyps, and other malignancies including
embryonic tumors and rhabdomyosarcoma. Many patients show signs reminiscent of neurofibromatosis
type 1 (NF1; 162200), particularly multiple cafe-au-lait macules (summary by Baas
et al., 2013). 'Turcot syndrome' classically refers to the combination of colorectal
polyposis and primary tumors of the central nervous system (Hamilton et al., 1995).
Trimbath et al. (2001) and Ostergaard et al. (2005) noted that the original definition
of Turcot syndrome may be too restrictive, and suggested that the full manifestation
of biallelic mutations in MMR genes includes the additional findings of early-onset
hematologic malignancies and cafe-au-lait spots suggestive of neurofibromatosis type
1 (NF1; 162200). Several authors have observed 2 main groups of so-called 'Turcot
syndrome.' Itoh and Ohsato (1985) noted that the colonic lesions seen in Turcot's
original cases were characterized by autosomal recessive inheritance and multiple
colonic polyps (up to 100), some of which exceeded 3 cm in diameter; the polyps frequently
showed malignant transformation in the second and third decades of life. A distinct
group of patients showed autosomal dominant inheritance of multiple small colonic
polyps similar to classic FAP; the CNS tumor in these patients appeared to be an additional
chance occurrence. Due to the similar phenotypes, FAP patients with brain tumors have
sometimes been referred to in the past as having 'Turcot syndrome' (see, e.g., Lewis
et al., 1983 and Lasser et al., 1994). Mastronardi et al. (1991) and Dupuis and Verellen-Dumoulin
(1995) also identified 2 distinct syndromes comprising polyposis and CNS tumors. One
shows autosomal recessive inheritance of polyps and gliomas, with CNS tumors as a
primary feature; this group includes the original kindred of Turcot et al. (1959).
The other group shows autosomal dominant FAP with CNS tumors, usually medulloblastomas,
as an extracolonic manifestation. The colonic polyps in Turcot syndrome occur earlier,
are less numerous and larger, and undergo malignant transformation earlier compared
to those in FAP. Paraf et al. (1997) also proposed that Turcot syndrome, which they
referred to as the 'brain tumor-polyposis (BTP) syndrome,' could be classified into
2 distinct entities. Patients with BTP syndrome type 1 have early onset of malignant
gliomas and colorectal adenomas without polyposis; these are non-FAP cases. Neoplasms
from these patients show DNA replication errors consistent with mutations in DNA mismatch
repair genes. In contrast, BTP syndrome type 2 includes patients in FAP kindreds who
develop CNS tumors. These patients have germline APC mutations which predispose to
brain tumors. Risk analysis showed an increased incidence of medulloblastoma in FAP
patients. By contrast, APC mutations were not found in sporadic glioma or medulloblastoma.
Wimmer and Etzler (2008) provided a review of the mismatch cancer repair syndrome
and suggested that the prevalence may be underestimated.;
Inheritance : Autosomal recessive;
Molecular basis : Caused by mutation in the DNA mismatch repair protein MLH1 gene (MLH1, 120436.0003); Caused by mutation in the mutS homolog 2 gene (MSH2, 609309.0014); Caused by mutation in the PMS1 homolog 2, mismatch repair system component gene (PMS2,
600259.0001); Caused by mutation in the mutS homolog 6 gene (MSH6, 600678.0012);
Neoplasia : Ependymoma; Glioblastoma; Oligodendroglioma; Neuroblastoma; Astrocytoma; Medulloblastoma; Basal cell carcinoma; Colonic adenocarcinoma; Leukemia; Lymphoma; Rhabdomyosarcoma;
Prefixed ID : #276300;
Origin ID : 276300;
UMLS CUI : C5399763;
Currated CISMeF NLP mapping
- DO Cross reference
- False automatic mappings
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- See also inter- (CISMeF)
- Semantic type(s)
- UMLS correspondences (same concept)
- Validated automatic mappings to NTBT
