Mutations in different genes encoding sarcomeric proteins are responsible for 50-60% of familial cases of hypertrophic cardiomyopathy (HCM); however, the genetic alterations causing the disease in one-third of patients are currently unknown. Here we describe a case with familial HCM of unknown cause. Whole-exome sequencing reveals a variant in the gene encoding the sarcomeric protein filamin C (p.A1539T) that segregates with the disease in this family. Sequencing of 92 HCM cases identifies seven additional variants segregating with the disease in eight families. Patients with FLNC mutations show marked sarcomeric abnormalities in cardiac muscle, and functional analysis reveals that expression of these FLNC variants resulted in the formation of large filamin C aggregates. Clinical studies indicate that FLNC-mutated patients have higher incidence of sudden cardiac death. On the basis of these findings, we conclude that mutations in the gene encoding the sarcomeric protein filamin C cause a new form of familial HMC.

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A patient is presented with a clinical syndrome of erythroderma, fever, liver function abnormalities, eosinophilia and atypical lymphocytosis due to carbamazepine hypersensitivity. Immunological analysis of peripheral blood mononuclear cells was performed using mouse monoclonal antibodies against T-cell and Ia antigens. A 12-fold increase in the absolute numbers of suppressor-cytotoxic T-cells was found, resulting in a reversed helper/suppressor ratio. Also the number of Ia-positive cells was greatly increased. Carbamazepine may induce a reversible proliferation and activation of the suppressor-cytotoxic subset of T-cells. Implications and pathogenetic possibilities are briefly discussed.

A 39-year-old man is described in whom osteonecrosis of the manubrium sterni developed 23 months and of a rib 25 months after treatment for Hodgkin's disease Stage IIIB with polychemotherapy and subdiaphragmatic radiotherapy. The radiologic and histologic characteristics of this very rare localization of steroid-associated osteonecrosis are discussed.

Caseous calcification of the mitral annulus is an infrequent echocardiographic finding. The differential diagnosis includes other entities like tumors, abscess or thrombus. Both cardiac CT and cardiac MRI may be useful for its definitive diagnosis.