Abstract
Lynch syndrome is the most common form of hereditary colorectal cancer (CRC). This review covers the cardinal features of Lynch syndrome with particular emphasis upon its diagnostic criteria, molecular genetics, natural history, genetic counseling, surveillance and management. Considerable attention has been given to the etiologic role of mismatch repair (MMR) genes as well as low penetrance alleles and modifier genes. The American founder mutation, a deletion of exons 1-6 of MSH2, is discussed in some detail, owing to its high frequency in the US (19 000-30 000 carriers). Genetic counseling is essential prior to patients - undergoing DNA testing and again when receiving their test results. Families with a lower incidence of CRC and extracolonic cancers, in the face of being positive for Amsterdam I criteria but who do not have MMR deficiency by tumor testing, are probably not Lynch syndrome, and thereby should preferably be designated as familial CRC of undetermined type. Patients who are either noncompliant or poorly compliant with colonoscopy, and who are MMR mutation positive, may be candidates for prophylactic colectomy, while MMR mutation-positive women who are noncompliant with gynecologic surveillance may be candidates for prophylactic hysterectomy and bilateral salpingo-oophorectomy.
| Original language | English |
|---|---|
| Pages (from-to) | 390-402 |
| Number of pages | 13 |
| Journal | European Journal of Human Genetics |
| Volume | 14 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2006 |
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All Science Journal Classification (ASJC) codes
- Genetics(clinical)
Cite this
Phenotypic and genotypic heterogeneity in the Lynch syndrome : Diagnostic, surveillance and management implications. / Lynch, Henry T.; Boland, C. Richard; Gong, Gordon; Shaw, Trudy G.; Lynch, Patrick M.; Fodde, Riccardo; Lynch, Jane F.; de la Chapelle, Albert.
In: European Journal of Human Genetics, Vol. 14, No. 4, 04.2006, p. 390-402.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Phenotypic and genotypic heterogeneity in the Lynch syndrome
T2 - Diagnostic, surveillance and management implications
AU - Lynch, Henry T.
AU - Boland, C. Richard
AU - Gong, Gordon
AU - Shaw, Trudy G.
AU - Lynch, Patrick M.
AU - Fodde, Riccardo
AU - Lynch, Jane F.
AU - de la Chapelle, Albert
PY - 2006/4
Y1 - 2006/4
N2 - Lynch syndrome is the most common form of hereditary colorectal cancer (CRC). This review covers the cardinal features of Lynch syndrome with particular emphasis upon its diagnostic criteria, molecular genetics, natural history, genetic counseling, surveillance and management. Considerable attention has been given to the etiologic role of mismatch repair (MMR) genes as well as low penetrance alleles and modifier genes. The American founder mutation, a deletion of exons 1-6 of MSH2, is discussed in some detail, owing to its high frequency in the US (19 000-30 000 carriers). Genetic counseling is essential prior to patients - undergoing DNA testing and again when receiving their test results. Families with a lower incidence of CRC and extracolonic cancers, in the face of being positive for Amsterdam I criteria but who do not have MMR deficiency by tumor testing, are probably not Lynch syndrome, and thereby should preferably be designated as familial CRC of undetermined type. Patients who are either noncompliant or poorly compliant with colonoscopy, and who are MMR mutation positive, may be candidates for prophylactic colectomy, while MMR mutation-positive women who are noncompliant with gynecologic surveillance may be candidates for prophylactic hysterectomy and bilateral salpingo-oophorectomy.
AB - Lynch syndrome is the most common form of hereditary colorectal cancer (CRC). This review covers the cardinal features of Lynch syndrome with particular emphasis upon its diagnostic criteria, molecular genetics, natural history, genetic counseling, surveillance and management. Considerable attention has been given to the etiologic role of mismatch repair (MMR) genes as well as low penetrance alleles and modifier genes. The American founder mutation, a deletion of exons 1-6 of MSH2, is discussed in some detail, owing to its high frequency in the US (19 000-30 000 carriers). Genetic counseling is essential prior to patients - undergoing DNA testing and again when receiving their test results. Families with a lower incidence of CRC and extracolonic cancers, in the face of being positive for Amsterdam I criteria but who do not have MMR deficiency by tumor testing, are probably not Lynch syndrome, and thereby should preferably be designated as familial CRC of undetermined type. Patients who are either noncompliant or poorly compliant with colonoscopy, and who are MMR mutation positive, may be candidates for prophylactic colectomy, while MMR mutation-positive women who are noncompliant with gynecologic surveillance may be candidates for prophylactic hysterectomy and bilateral salpingo-oophorectomy.
UR - http://www.scopus.com/inward/record.url?scp=33646196845&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646196845&partnerID=8YFLogxK
U2 - 10.1038/sj.ejhg.5201584
DO - 10.1038/sj.ejhg.5201584
M3 - Review article
C2 - 16479259
AN - SCOPUS:33646196845
VL - 14
SP - 390
EP - 402
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 4
ER -