Lynch Syndrome.

Authors

Kohlmann W¹, Gruber SB².

Editors

In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors.

Source

GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2004 Feb 5 [updated 2018 Apr 12].

Author information

1: University of Utah Huntsman Cancer Institute, Salt Lake City, Utah
2: USC Norris Comprehensive Cancer Center, Los Angeles, California

Excerpt

CLINICAL CHARACTERISTICS:

Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following lifetime risks for cancer are seen: CRC: 52%-82% (mean age at diagnosis 44-61 years). Endometrial cancer in females: 25%-60% (mean age at diagnosis 48-62 years). Gastric cancer: 6%-13% (mean age at diagnosis 56 years). Ovarian cancer: 4%-12% (mean age at diagnosis 42.5 years; ~30% are diagnosed < age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.

DIAGNOSIS/TESTING:

The diagnosis of Lynch syndrome is established in a proband by identification of a germline heterozygous pathogenic variant in MLH1, MSH2, MSH6, or PMS2 or an EPCAM deletion on molecular genetic testing.

MANAGEMENT:

Treatment of manifestations: For colon cancer, full colectomy with ileorectal anastomosis is recommended. Other tumors are managed as in the general population. Prevention of primary manifestations: Prophylactic hysterectomy and bilateral salpingo-oophorectomy can be considered after childbearing is completed. Prophylactic colectomy prior to the development of colon cancer is generally not recommended for individuals known to have Lynch syndrome because screening colonoscopy with polypectomy is an effective preventive measure. Surveillance: Colonoscopy with removal of precancerous polyps every one to two years beginning between age 20 and 25 years or two to five years before the earliest age of diagnosis in the family, whichever is earlier. The efficacy of surveillance for cancer of the endometrium, ovary, stomach, duodenum, distal small bowel, urinary tract, and central nervous system is unknown. Agents/circumstances to avoid: Cigarette smoking. Evaluation of relatives at risk: When a diagnosis of Lynch syndrome has been confirmed in a proband, molecular genetic testing for the Lynch syndrome-related pathogenic variant should be offered to first-degree relatives to identify those who would benefit from early surveillance and intervention. Although molecular genetic testing for Lynch syndrome is generally not recommended for at-risk individuals younger than age 18 years, a history of early cancers in the family may warrant predictive testing prior to age 18.

GENETIC COUNSELING:

Lynch syndrome is inherited in an autosomal dominant manner. The majority of individuals diagnosed with Lynch syndrome have inherited the condition from a parent. However, because of incomplete penetrance, variable age of cancer development, cancer risk reduction as a result of screening or prophylactic surgery, or early death, not all individuals with a pathogenic variant in one of the genes associated with Lynch syndrome have a parent who had cancer. Each child of an individual with Lynch syndrome has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the pathogenic variant in the family is known.