Hereditary diffuse gastric cancer (HDGC) has been shown to be caused by germline mutations in the gene CDH1 located at 16q22.1, which encodes the cell-cell adhesion molecule, E-cadherin. Not only does loss of expression of E-cadherin account for the morphologic differences between intestinal and diffuse gastric cancer (DGC) variants, but it also appears to lead to distinct cellular features which appear to be common amongst related cancers that have been seen in the syndrome. As in most hereditary cancer syndromes, multiple organ sites may be commonly affected by cancer, in HDGC, lobular carcinoma of the breast (LBC) and possibly other organ sites have been shown to be associated with the familial cancer syndrome. Given the complexity of HDGC, not only with regard to the management of the DGC risk, but also with regard to the risk for other related cancers, such as LBC, a multi-disciplinary approach is needed for the management of individuals with known CDH1 mutations.

Introduction: The objective of this study was to identify the pattern of neurological deficits and document electrophysiological changes in women with macromastia. Methods: Patients with macromastia and neurological complaints underwent clinical evaluation and electrodiagnostic (EDx) studies of the upper limbs. Results: Findings include low‐amplitude medial antebrachial cutaneous (MACN) sensory nerve action potentials (SNAPs) and median compound muscle action potentials (CMAPs) and chronic denervation changes in the bilateral abductor pollicis brevis (APB) muscles on needle electrode examination (NEE), indicating axonal loss in the bilateral T1 distribution. Conclusions: The EDx data are in keeping with lesions involving bilateral T1 anterior primary rami (APR). Potential sites of compromise of the T1 APR are discussed. Further study of the effect of treatment for macromastia on the clinical and EDx findings is proposed. Muscle Nerve, 2013

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414 Background: The identification of Lynch syndrome carriers is an unmet medical need. Large studies characterizing family history profiles of unaffected individuals diagnosed with Lynch syndrome in the absence of a known family mutation have not been reported. Methods: We queried our laboratory database for unaffected patients who underwent Lynch syndrome genetic testing between September 2010 and May 2013 and had a positive test result. All individuals underwent full sequence and large rearrangement analysis of MLH1 and MSH2, and full sequence analysis of MSH6. Some patients also underwent full sequence and large rearrangement analysis of PMS2 and large rearrangement analysis of MSH6 and EPCAM. Those being tested for a known mutation in the family and patients undergoing single gene testing were excluded. We assessed family history profiles in 200 unaffected patients with genetically confirmed Lynch syndrome. Results: Of the 200 patients, 162 female and 38 male Lynch syndrome carriers were identified. Mutations in MLH1 and MSH2 were the most common (30.0% and 32.5%) while mutations in MSH6, PMS2, and EPCAM accounted for 21.0%, 13.5%, and 3.0% of all deleterious mutations, respectively. Eighteen patients did not have a first or second degree relative with colorectal cancer. Only 37.8% (73/193) of individuals had a first- or second-degree relative meeting the Amsterdam II criteria and 76.8 % (149/194) of individuals had a first or second degree relative meeting the Revised Bethesda criteria. The average PREMM1,2,6 score was 10.0% with 43.5% (87/200) falling below 5%. In this large cohort, 15.5% (31/200) had neither a first or second degree relative who met the Amsterdam II or Revised Bethesda criteria nor a PREMM1,2,6 score of 5% or greater. Conclusions: In order to improve detection of Lynch syndrome in the population, it is important to consider genetic testing in unaffected individuals even in the absence of a known family mutation. Development of guidelines that include having a single affected relative and extra-colonic cancers is needed to support healthcare providers in identifying appropriate patients for testing.