BACKGROUND AND PURPOSE: Arg179His mutations in ACTA2 are associated with a distinctive neurovascular phenotype characterized by a straight course of intracranial arteries, absent basal Moyamoya collaterals, dilation of the proximal internal carotid arteries, and occlusive disease of the terminal internal carotid arteries. We now add to the distinctive neuroimaging features in these patients by describing their unique constellation of brain malformative findings that could flag the diagnosis in cases in which targeted cerebrovascular imaging has not been performed. MATERIALS AND METHODS: Neuroimaging studies from 13 patients with heterozygous Arg179His mutations in ACTA2 and 1 patient with pathognomonic clinicoradiologic findings for ACTA2 mutation were retrospectively reviewed. The presence and localization of brain malformations and other abnormal brain MR imaging findings are reported. RESULTS: Characteristics bending and hypoplasia of the anterior corpus callosum, apparent absence of the anterior gyrus cinguli, and radial frontal gyration were present in 100% of the patients; flattening of the pons on the midline and multiple indentations in the lateral surface of the pons were demonstrated in 93% of the patients; and apparent "squeezing" of the cerebral peduncles in 85% of the patients. CONCLUSIONS: Because ␣-actin is not expressed in the brain parenchyma, only in vascular tissue, we speculate that rather than a true malformative process, these findings represent a deformation of the brain during development related to the mechanical interaction with rigid arteries during the embryogenesis.
Background Oculodentodigital dysplasia (ODDD) is a rare disorder with pleiotropic effects involving multiple body systems, caused by mutations in the gap junction protein alpha 1 (GJA1) gene. GJA1 gene encodes a polytopic connexin membrane protein, Cx43, that is a component of connexon membrane channels. Methods We describe two unrelated female probands referred for a genetic review in view of a dysmorphic clinical phenotype. Results Two novel missense mutations in GJA1 that substitute conserved amino acids in the first and second transmembrane domains (NM_000165.5: c.77T>C p.Leu26Pro and NM_000165.5:c.287T>G p.Val96Gly) were detected through targeted sequencing of GJA1. These variants were detected in the heterozygous state in the two Maltese probands and segregated with the disease phenotype. Conclusion This report further expands the mutational spectrum of ODDD.
Thalidomide is an effective chemotherapeutic agent used to achieve remission in multiple myeloma. However, its administration is associated with several adverse effects including venous thromboembolism, while arterial thrombosis has also, although rarely, been described in the literature. We report a case of internal carotid artery occlusion within 1 week of starting thalidomide with prophylactic low molecular weight heparin in a patient who had no other prothrombotic risk factors. It is not known why this complication occurs despite the administration of anticoagulant prophylaxis. The role of factor VIII, von Willebrand factor antigen levels and fibrinogen in multiple myeloma patients should be studied in order to determine if these factors should be targeted in future prophylactic treatment. LEARNING POINTS• Thalidomide increases risk of arterial thrombosis in multiple myeloma (MM), even if no other procoagulant risk factors are present.• All patients starting thalidomide must be assessed before commencing venous thromboprophylaxis, although its efficacy in preventing arterial thrombosis has not yet been proven. • Further research is required to target anti-thrombotic factors in order to prevent arterial thrombosis in patients with MM being treated with thalidomide and its derivatives. KEYWORDS Multiple myeloma; thalidomide; arterial thrombosis; cerebrovascular accident. CASE REPORTA 45-year-old woman presented with mild lethargy, fatigue and generalised myalgia, but had an otherwise unremarkable history. Upon investigation, she was found to be mildly cytopenic with a haemoglobin level of 11.3 g/dl and a platelet count of 69×10 9 /l. Her peripheral blood film revealed a left shift in the neutrophils and erythrocyte anisopoikilocytosis with occasional teardrop red cells. Haematinics, an autoimmune antibody screen and viral screens were negative. Further investigations ultimately confirmed the presence of multiple myeloma (MM). METHODS AND PROCEDURESSerum protein electrophoresis demonstrated hypogammaglobulinaemia and an initial low level of paraprotein which later increased to 3 g/l.
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