Multiple Symmetric Lipomatosis: clinical aspects and outcome in a longterm longitudinal study

BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disease characterized by the growth of uncapsulated masses of adipose tissue. MSL is associated with high ethanol intake and complicated by somatic and autonomic neuropathy and by the infiltration of the adipose tissue at the mediastinal level. To date, the disease is considered as slowly progressive, but long-term longitudinal data are still lacking. In this study, a long-term follow-up of a large series of MSL patients is presented. METHODS: We studied 31 patients with MSL (30 males and one female) first evaluated at our institution from 1973 to 1992. All patients were followed until 1998-1999 or until death, with a mean follow-up of 14.5+/-5.0 y (range 4-26 y). Both at baseline and during follow-up, the location and the size of the subcutaneous lipomatous fat depots, the presence and the extension of deeply localized lipomatous tissue, and the presence and the severity of both somatic and autonomic neuropathy were evaluated. RESULTS: Eight MSL patients died during follow-up (25.8% of patients). A sudden death was proved to be the cause of death in three patients. All these three patients had severe autonomic neuropathy and none had coronary disease, acute myocardial infarction or other cardiac abnormalities. No signs or symptoms of coronary heart disease were present in the whole series. In addition to this high fatality rate, a substantial morbidity related to the occupation of the mediastinal space by the lipomatus tissue and to somatic neuropathy was also observed. CONCLUSIONS: MSL is associated with a significant morbidity and mortality. Therefore, the definition of 'benign symmetric lipomatosis', still adopted by several authors, cannot be justified

Analysis of shared heritability in common disorders of the brain

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology