Neoplasms in Myotonic Dystrophy. C. Mueller¹, R.T. Moxley², J. Hilbert², M.H. Greene¹. 1) Clinical Genetics Branch, DCEG, NCI, NIH, Bethesda, MD; 2) Department of Neurology, Department of Neurology, University of Rochester Medical Center, Rochester, NY.
   Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults, affecting about 1 in 8,000 individuals. In addition to muscular weakness, atrophy and myotonia, there are a myriad of clinical features including cardiac conduction defects, respiratory insufficiency, cataracts, diabetes, reduced immunoglobulins, frontal balding, testicular atrophy, and varying degrees of mental impairment. DM1 is the result of an unstable trinucleotide (CTG) expansion in the 3 untranslated region of the dystrophia myotonic-protein kinase (DMPK) gene, located on chromosome 19q13.3. In reflecting on our clinical experience, we have wondered whether there might be an increased incidence of tumors in patients with DM1. There have been multiple case reports of DM1 and pilomatrixoma, a benign calcifying cutaneous tumor thought to be derived from hair matrix cells. We present a comprehensive literature review of reported pilomatrixomas and various other neoplasms that have been observed in patients with DM1. We also present our initial analysis of tumors reported by DM1 patients enrolled in the NIH sponsored National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members. Pilomatrixomas emerged as the strongest candidate for a genuine molecular relationship to DM1, which gained support from the occurrence of pilomatrixomas in patients with Rubinstein-Taybi syndrome and Gardner syndrome, both of which are associated with the development of various neoplasms. The other most common tumor types implicated, based on our findings include thymoma, adenomas of the parotid, pituitary, parathyroid, pancreas and thyroid glands, as well as multiple basal cell carcinomas. This constellation of tumors also led us to our hypothesis that dysregulation of the Wnt/-catenin signaling pathway may be the molecular basis for this relationship, as it has been implicated in the development of pilomatrixomas in the disorders under consideration, in sporadic pilomatrixomas, and in a number of the other neoplasms that have been reported in DM1 patients.