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Lynch syndrome: still not a familiar picture.

Hes FJ - World J Surg Oncol (2008)

Bottom Line: It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients.Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics.Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Human and Clinical Genetics (CHKG), Department of Clinical Genetics, Leiden University Medical Center (LUMC), RC Leiden, The Netherlands. f.j.hes@lumc.nl

ABSTRACT

Background: Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems.

Case presentation: A large Lynch syndrome family with 15 affected family members and involvement in 7 organs is reported. It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients. None of the described family members underwent presymptomatic screening on the basis of the family history.

Conclusion: Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics. For Lynch syndrome, these features can be found in the Amsterdam and Bethesda criteria. Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

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Pedigree of a Lynch syndrome family, showing organ systems and age of diagnosis, see legend. Year, year of diagnosis/diagnoses; asterisk, anamnestically obtained information; urinary tract, urothelial carcinoma of renal pelvis or ureter; skin, keratoacanthoma; asc., ascending colon; transv., transverse colon; desc., descending colon.
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Figure 1: Pedigree of a Lynch syndrome family, showing organ systems and age of diagnosis, see legend. Year, year of diagnosis/diagnoses; asterisk, anamnestically obtained information; urinary tract, urothelial carcinoma of renal pelvis or ureter; skin, keratoacanthoma; asc., ascending colon; transv., transverse colon; desc., descending colon.

Mentions: In November 2006, a 56-year old woman (III-1 in pedigree, Figure 1) visited our clinic for genetic counseling because she was worried about the many cases of cancer that had occurred in her family. The direct reason for her visit was the recent death of her 39-year old son (IV-1) with a symptomatic, and already metastasized, rectal adenocarcinoma. The counselee had been diagnosed with an endometrial and a sigmoid carcinoma at age 53- and 54-years old, respectively. She reported her overwhelming family history, which easily fulfilled the criteria that enable selection of families that are at risk for Lynch syndrome (Table 1). Subsequent IHC-analysis on archival tumor material of her sigmoid carcinoma demonstrated abrogation of the MSH2 and MSH6 proteins, which is typically associated with a germline MSH2 mutation. Multiplex ligation-dependent probe amplification (MLPA), in DNA extracted from peripheral lymphocytes, identified an entire MSH2 gene deletion (exons 1–16) and confirmed the diagnosis of Lynch syndrome.


Lynch syndrome: still not a familiar picture.

Hes FJ - World J Surg Oncol (2008)

Pedigree of a Lynch syndrome family, showing organ systems and age of diagnosis, see legend. Year, year of diagnosis/diagnoses; asterisk, anamnestically obtained information; urinary tract, urothelial carcinoma of renal pelvis or ureter; skin, keratoacanthoma; asc., ascending colon; transv., transverse colon; desc., descending colon.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2265717&req=5

Figure 1: Pedigree of a Lynch syndrome family, showing organ systems and age of diagnosis, see legend. Year, year of diagnosis/diagnoses; asterisk, anamnestically obtained information; urinary tract, urothelial carcinoma of renal pelvis or ureter; skin, keratoacanthoma; asc., ascending colon; transv., transverse colon; desc., descending colon.
Mentions: In November 2006, a 56-year old woman (III-1 in pedigree, Figure 1) visited our clinic for genetic counseling because she was worried about the many cases of cancer that had occurred in her family. The direct reason for her visit was the recent death of her 39-year old son (IV-1) with a symptomatic, and already metastasized, rectal adenocarcinoma. The counselee had been diagnosed with an endometrial and a sigmoid carcinoma at age 53- and 54-years old, respectively. She reported her overwhelming family history, which easily fulfilled the criteria that enable selection of families that are at risk for Lynch syndrome (Table 1). Subsequent IHC-analysis on archival tumor material of her sigmoid carcinoma demonstrated abrogation of the MSH2 and MSH6 proteins, which is typically associated with a germline MSH2 mutation. Multiplex ligation-dependent probe amplification (MLPA), in DNA extracted from peripheral lymphocytes, identified an entire MSH2 gene deletion (exons 1–16) and confirmed the diagnosis of Lynch syndrome.

Bottom Line: It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients.Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics.Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Human and Clinical Genetics (CHKG), Department of Clinical Genetics, Leiden University Medical Center (LUMC), RC Leiden, The Netherlands. f.j.hes@lumc.nl

ABSTRACT

Background: Germ line mutations in mismatch repair genes underlie Lynch syndrome and predispose carriers for colorectal carcinoma and malignancies in many other organ systems.

Case presentation: A large Lynch syndrome family with 15 affected family members and involvement in 7 organs is reported. It illustrates a lack of awareness and knowledge about this hereditary tumor syndrome among doctors as well as patients. None of the described family members underwent presymptomatic screening on the basis of the family history.

Conclusion: Hereditary features, like young age at diagnosis, multiple tumors in multiple organs and a positive family history, should lead to timely referral of suspected cases for genetic counseling and diagnostics. For Lynch syndrome, these features can be found in the Amsterdam and Bethesda criteria. Subsequently, early identification of mutation carriers might have diminished, at least in part, the high and early morbidity and mortality observed in this family.

Show MeSH
Related in: MedlinePlus