GLIOMA-01 GENETIC INVESTIGATIONS AND COUNSELING IN FAMILIAL MSS TURCOT SYNDROME ASSOCIATED TO INFERTILITY AND CHILD MORTALITY

Abstract

Abstract The aim of this study was to report MSI genetic findings in a three-generation Tunisian pedigree of Turcot syndrome 1 (TS1), characterized by an uncommon association with infertility and child mortality. Microsatellite instability testing and genetic counseling were offered to affected members and their young relatives, to provide optimal clinical and preventive care. The index case of our Tunisian pedigree was a 38 year-old female, in whom histologic assessment of endoscopic specimens through a colorectal adenoma resection during screening colonoscopy, showed a tubular adenoma of the lower rectum with low-grade intraepithelial neoplasia. The screening procedure was conducted because her two brothers, 58 and 60 years old, harbored respectively glioblastoma multiforme and colon adenocarcinoma. The first brother exhibited an intracranial hypertension syndrome and a left hemiplegia leading to the diagnosis of a brain tumor. Whereas the second brother manifested diarrhea and intestinal colic that were investigated by colonoscopy. Histologic assessment of endoscopic specimens through a right preangular budding formation showed a well-differentiated liberkhunian adenocarcinoma that was treated by a right hemicolectomy. Genetic assessment at the germinal and somatic levels was conducted for the three affected patients using conventional microsatellite instability (MSI) testing methods. bMolecular analysis determined MSI status of the tumors and classified them into stable types (MSS) without any mutation or aberrant expression of MLH1, MSH2, MSH6, and PMS2 genes. Familial history revealed, at the first generation, a consanguineous couple who lost several children at a young age. This couple gave birth to eight children, three of whom were infertile, three affected by MMS TS1 and two healthy. The third generation consists of 15 children, so far, without any tumors. Genetic counselling for TS remains difficult because of the rarity of the condition, its shifting definition over the years, and its genetic and phenotypic heterogeneity.