Biallelic mismatch repair (MMR) gene mutations cause a distinct clinical syndrome that predisposes individuals to childhood-onset brain tumors, leukemia, lymphoma and gastrointestinal cancers. Looking at cases published in the literature, the majority of biallelic MMR-gene mutation carriers manifest cutaneous features of Neurofibromatosis type 1 (NF1), most commonly cafe-au-lait macules (CAL). The majority of individuals with MMR biallelic gene mutations do not meet the National Institutes of Health (NIH) clinical diagnostic criteria for NF1. Identifying individuals with biallelic MMR mutations prior to a cancer diagnosis is difficult. Individuals with multiple CAL maybe evaluated for NF1 through a genetics or NF specific clinic. Patient charts from a pediatric neurofibromatosis clinic were reviewed to identify individuals who did not meet the NIH clinical diagnostic criteria for NF1. Parents/legal guardians of patients who did not meet NF1 diagnostic criteria were re-contacted and asked to provide an extended family history of cancer. Families with a proband diagnosed with cancer or with a family history of Lynch syndrome-related cancers were referred to the Familial Gastrointestinal Cancer Registry (FGICR) for genetic counseling and possible genetic testing. Eighty-three family histories were obtained, 69 of these families were positive for a family history of cancer. Eight families were referred to the FGICR. Genetic testing is ongoing at the time of this report. Results of this study will hopefully provide information regarding potential early identification of children with biallelic MMR mutations.described features: (1) six or more cafe-au-lait macules (CAL) (over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals), (2) two or ... 2007). The children seldom have more than one feature of NF1, thus generally they do not meet the full diagnostic criteria of NF1 (Wimmer and Etzler 2008). ... There is no consensus on a proper name, so in this paper, I will use CMMR-D syndrome, a comprehensive and accurate name.
|Title||:||Biallelic Mismatch Repair Gene Mutations in a Neurofibromatosis Patient Population|
|Publisher||:||ProQuest - 2009|