Diagnosis Lynch syndrome lacks overt phenotypic markers, therefore,accurate family history is crucial If the clinical pattern of disease in the family is positive,molecular studies are performed to detect microsatellite instabilities and germline mutations (MSH2,MLH1,MSH6)that segregate in affected family members. MSH6 accounts for 10%of Lynch syndrome mutations and is associated with milder disease, but an excess of endometrial cancer. Patients must meet the Amsterdam criteria to be diagnosed,and the Bethesda criteria to undergo microsatellite testing
TPrevention and treatment outside of genetic testing/screening Colonoscopy beginning at age 25,repeated annually Endometrial aspiration biopsy annually and transvaginal ultrasound with serum CA-125 measurements once or twice per year Prophylaxis 0 Prophylactic colectomy- offered to patients with high- risk mutations or to patients who may not be compliant 0 Prophylactic hysterectomy with bilateral salpingo- oophorectomy
References 1.Lynch HT,Lynch JF."What the Physician Needs to Know About Lynch Syndrome:an Update". Oncology.April 2005.Vol.19.No.4.pp.455-469. ■ 2.Hampel,et al."Screening for the Lynch Syndrome"N.Engl J Med 352;18:1851-60. 3.Lu KH,Dinh M,et al."Gynecologic Cancer as a 'Sentinel Cancer'for Women With HNPCC syndrome".Obs Gyn_105;3:569-574. ■ 4.Offit,Kauff."Reducing the Risk of Gynecologic Cancer in the Lynch Syndrome"N Engl J Med 354:3:293-295
Li-Fraumeni Syndrome Studies by Li and Fraumeni led to first evidence of inherited predisposition to cancer.(MIM 151623) Breast tumors Sarcoma,leukemia,lung cancer,and adrenal cortical carcinoma
Li-Fraumeni Syndrome Studies by Li and Fraumeni led to first evidence of inherited predisposition to cancer. (MIM 151623) ❖ Breast tumors ❖ Sarcoma, leukemia, lung cancer, and adrenal cortical carcinoma
What is Li-Fraumeni syndrome? Li-Framenisyndrome isa rare isorder that greatly increases the risk of developing several types ofcr,particuarly in children and young adults. The cancers most oftn associated with Li-Fraumeni syndrome inchude breast cancer.aform of bone cancer called osteosarcoma,and cancers of soft tissues(such as muscle)called soft tissue sarcomas.Other cancers commonly seen in this syndrome inchude brain tumors,cancers of blood-forming tissues (leukemias),and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands(small hormone-producing glands on top of each kidney). Several other types of cancer asoocrmore frequny n people with Li-Fraumeni syndrome. A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome Both cosificanly increase the chances of developing multiple cancers beginningn chilhood:however,the patter of specific cancers seen in affected family members is different. How common is Li-Fraumeni syndrome? The exact prevalence of Li-Frameis kow.One U.S.registry of Li-Fraisyrome patients sugeststhat about 00peopleom6famies have thisisorder