DGM (Dutch-German Mennonite)

Inheritance: autosomal dominant
Genes: MLH1

MLH1
HNPCC
HPNCC2

Colon cancer

Malignancies

Hereditary Non-Polyposis Colon Cancer

Clinical Characteristics

General description (for patients):

Increased risk for cancer comes from many mechanisms.  This disorder is primarily expressed as colon cancer but it is not uncommon for a patient to develop tumors in multiple organs at various times.  The basic mechanism seems to be a defect in a protein important to the repair of DNA when new DNA is synthesized during cell division.

Medical description:  

This is one of two mutations that specifically seem to increase the risk of colon cancer (see also adenomatous polyposis of the colon OMIM #175100).  A defect in the repair mechanism of DNA replication seems to be the underlying basis.  In this disorder, it is not unusual for colon cancer to appear in the first two decades of life, and for multiple extra-colonic tumors to occur in individuals throughout their lifetimes, including intracranial tumors, neurofibromatosis, lymphomas, and hematologic malignancies, as well as in various female reproductive organs.

Genetics:

A mutation in MLH1 gene seems to confer increased risk for cancer, principally in the colon.  MLH1 is located on chromosome 3 (3p22.2) and its protein product acts as part of a mismatch repair mechanism of replication errors in DNA.   The mutations are manifest in the heterozygous state leading to autosomal dominant pedigree patterns although individuals with homozygous mutations have been reported.  Several Canadian Mennonite families of Dutch-German background with a c.2141G>A substitution have been identified.

Treatment:

The primary treatment is removal of tumors when they are diagnosed.

Prognosis:

Largely dependent on the nature of the individual tumors.

Ancillary treatments and support:

Dependent upon tumors and general health.

Specialists and specialty centers:

Gastroenterologist, internist, oncologist.

References:

Orton, N.C., Innes, A.M., Chudley, A.E., and Bech-Hansen, N.T.:  Unique disease heritage of the Dutch-German Mennonite population.  Am. J. Med. Genet. 146A: 1072-1087, 2008.  PubMed ID: 18348259

Taylor, C.F., Charlton, R.S., Burn, J., Sheridan, E., and Taylor, G.R.:  Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA.  Hum. Mutat. 22: 428-433, 2003.  PubMed ID: 14635101

Resources:

Hereditary Non-Polyposis Colorectal Cancer
Genetics Home Reference

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