Phenotypic and genotypic heterogeneity in the Lynch syndrome

Diagnostic, surveillance and management implications

Henry T. Lynch, C. Richard Boland, Gordon Gong, Trudy G. Shaw, Patrick M. Lynch, Riccardo Fodde, Jane F. Lynch, Albert de la Chapelle

Research output: Contribution to journalReview article

118 Citations (Scopus)

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 languageEnglish
Pages (from-to)390-402
Number of pages13
JournalEuropean Journal of Human Genetics
Volume14
Issue number4
DOIs
StatePublished - Apr 2006

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Hereditary Nonpolyposis Colorectal Neoplasms
DNA Mismatch Repair
Colorectal Neoplasms
Genetic Counseling
Modifier Genes
Mutation
Penetrance
Colectomy
Sequence Deletion
Ovariectomy
Colonoscopy
Natural History
Hysterectomy
Molecular Biology
Exons
Neoplasms
Alleles
DNA
Incidence
Genes

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 journalReview article

Lynch, Henry T. ; Boland, C. Richard ; Gong, Gordon ; Shaw, Trudy G. ; Lynch, Patrick M. ; Fodde, Riccardo ; Lynch, Jane F. ; de la Chapelle, Albert. / Phenotypic and genotypic heterogeneity in the Lynch syndrome : Diagnostic, surveillance and management implications. In: European Journal of Human Genetics. 2006 ; Vol. 14, No. 4. pp. 390-402.
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