Tuberous sclerosis associated with multiple hepatic lipomatous tumors and hemorrhagic renal angiomyolipoma.
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We report a case of tuberous sclerosis associated with hepatic lipomatous tumors and renal angiomyolipomas. Abdominal ultrasonography revealed a high echoic large tumor in the left kidney. A provisional diagnosis of angiomyolipomas of the kidney was made based on computed tomography. Subsequent laparotomy revealed that the extracted tumor was renal angiomyolipoma. It was also revealed that there was an association with hepatic lipomatous tumors thought to be lipomas or angiomyolipomas by liver biopsy. Nearly half of all cases of angiomyolipoma in the kidney are reported as occasional association with tuberous sclerosis complex, but lipomatous tumors in the liver are rare. (+info)
MR imaging of tuberous sclerosis in neonates and young infants.
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BACKGROUND AND PURPOSE: The MR imaging appearance of intracranial manifestations in tuberous sclerosis varies with age. The aim of this study was to specify MR characteristics in a coherent group of neonates and infants in order to distinguish them from the mature pattern. METHODS: The MR studies of seven patients under 3 months old were reviewed retrospectively. Imaging appearance, number, and distribution of tubers, white matter anomalies, subependymal nodules, and subependymal giant cell astrocytomas were analyzed. RESULTS: All patients had more white matter anomalies, subependymal nodules, subependymal giant cell astrocytomas, transmantle dysplasias, and left-hemispheric and temporal lesions, but less cortical tubers than did older patients in previous series. The lesions were easy to detect as hyperintense foci on T1-weighted images. Visibility as hypointensities on T2-weighted images was comparatively poor. CONCLUSION: The nodular subependymal and linear parenchymal tuberous sclerosis lesions in infants under 3 months old are hyperintense on T1-weighted images and hypointense on T2-weighted images as opposed to the reverse pattern of signal intensity in older persons. The scarce myelination helps to identify white matter anomalies, which become less visible as myelination progresses. Conversely, purely intracortical tubers are more difficult to diagnose in infants. Because the overall number and conspicuity of all other lesions in our series were greater than in previous series with older subjects, our findings indicate that infant age does not compromise, but facilitates, the correct MR diagnosis of tuberous sclerosis. Therefore, if tuberous sclerosis is clinically suspected within the first 3 months of life, imaging should not be delayed. (+info)
Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background.
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Tuberous sclerosis (TSC) is an autosomal dominant genetic disorder in which benign hamartomas develop in multiple organs, caused by mutations in either TSC1 or TSC2. We developed a murine model of Tsc2 disease using a gene targeting approach. Tsc2-null embryos die at embryonic days 9.5-12.5 from hepatic hypoplasia. Tsc2 heterozygotes display 100% incidence of multiple bilateral renal cystadenomas, 50% incidence of liver hemangiomas, and 32% incidence of lung adenomas by 15 months of age. Progression to renal carcinoma, fatal bleeding from the liver hemangiomas, and extremity angiosarcomas all occur at a rate of less than 10%. The renal cystadenomas develop from intercalated cells of the cortical collecting duct and uniformly express gelsolin at high levels, enabling detection of early neoplastic lesions. The tumor expression pattern of the mice is influenced by genetic background, with fewer large renal cystadenomas in the outbred Black Swiss background and more angiosarcomas in 129/SvJae chimeric mice. The slow growth of the tumors in the heterozygote mice matches the limited growth potential of the great majority of TSC hamartomas, and the influence of genetic background on phenotype correlates with the marked variability in expression of TSC seen in patients. (+info)
Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin.
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Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by a broad phenotypic spectrum that includes seizures, mental retardation, renal dysfunction and dermatological abnormalities. Mutations to either the TSC1 or TSC2 gene are responsible for the disease. The TSC1 gene encodes hamartin, a 130-kDa protein without significant homology to other known mammalian proteins. Analysis of the amino acid sequence of tuberin, the 200-kDa product of the TSC2 gene, identified a region with limited homology to GTPase-activating proteins. Previously, we demonstrated direct binding between tuberin and hamartin. Here we investigate this interaction in more detail. We show that the complex is predominantly cytosolic and may contain additional, as yet uncharacterized components alongside tuberin and hamartin. Furthermore, because oligomerization of the hamartin carboxyl-terminal coiled coil domain was inhibited by the presence of tuberin, we propose that tuberin acts as a chaperone, preventing hamartin self-aggregation. (+info)
Prenatal detection of cerebral lesions in a fetus with tuberous sclerosis.
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We report a newborn, diagnosed prenatally with both cardiac rhabdomyomas and a brain tumor. To the best of our knowledge, this is the first report of central nervous system (CNS) lesions detected prenatally in a child with tuberous sclerosis with term follow-up. At 36 months, the child has normal growth and is developing appropriately. Thus the finding of CNS tumors on fetal ultrasound examination can help in the prenatal diagnosis of tuberous sclerosis but does not necessarily indicate a poor prognosis. (+info)
Mutational analysis of the tuberous sclerosis gene TSC2 in patients with pulmonary lymphangioleiomyomatosis.
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Pulmonary lymphangioleiomyomatosis (LAM) is a rare disorder limited almost exclusively to women of reproductive age. LAM affects about 5% of women with tuberous sclerosis complex (TSC). LAM also occurs in women who do not have TSC (sporadic LAM). TSC is a tumour suppressor gene syndrome characterised by seizures, mental retardation, and tumours in the brain, heart, and kidney. Angiomyolipomas, which are benign tumours with smooth muscle, fat, and dysplastic vascular components, are the most common renal tumour in TSC. Renal angiomyolipomas also occur in 63% of sporadic LAM patients. We recently found that 54% of these angiomyolipomas have TSC2 loss of heterozygosity, leading to the hypothesis that sporadic LAM is genetically related to TSC. In this study, we screened DNA from 21 women with sporadic LAM for mutations in all 41 exons of TSC2. Twelve of the patients had known renal angiomyolipomas. No TSC2 mutations were detected. We did find three silent TSC2 polymorphisms. We conclude that patients with sporadic LAM, including those with renal angiomyolipomas, do not have a high frequency of germline mutations in the coding region of TSC2. (+info)
Recognizing an index case of tuberous sclerosis.
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Tuberous sclerosis is the most common neurocutaneous syndrome after neurofibromatosis. Dermatologic manifestations may be the only clues the family physician has to the diagnosis of the disorder, which is also marked by childhood seizures and mental retardation. Characteristic signs of tuberous sclerosis vary widely in severity and can include hypopigmented "ash-leaf spots," fibrous plaques on the forehead, angiofibromas on the face (adenoma sebaceum), a shagreen patch on the lower back and fibromas of the nails. Computed tomographic scanning or magnetic resonance imaging reveal subependymal nodules or cortical "tubers" in the brain. Associated cardiac, retinal, renal and pulmonary pathology can increase morbidity and mortality. Genetic counseling is helpful but has limited use because of the variation in genetic expression and the frequency of new gene mutations that cause this disorder. (+info)
Tuberous sclerosis: differences between cerebral and cerebellar cortical tubers in a pediatric population.
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BACKGROUND AND PURPOSE: Histologic evidence of cortical tubers is pathognomonic of tuberous sclerosis (TS) disease. Cerebellar tubers, however, are uncommonly found. Our objective was to evaluate the prevalence and characteristics of cerebellar tubers in a large series of pediatric patients with TS studied with MR imaging. In particular, their relationship with volume loss and age will be analyzed. METHODS: MR images of 34 children with TS and cortical tubers were reviewed. There were 17 female and 17 male patients. The mean age was 8.9+/-4.5 years (mean +/- SD), with a range from 2 to 14 years. The number and location (supratentorial, infratentorial) of tubers and volume loss of the underlying parenchyma were recorded. The relationship between tuber location, patient age, and number of tubers was studied using the Student's t test for independent samples. The relationship between tuber location and presence of volume loss was established using the Pearson chi2 test. RESULTS: The mean number of cortical tubers was 14.3+/-8.5. Fifteen (44.1%) patients had cerebellar tubers associated with cerebral lesions. Patients with cerebellar and cerebral tubers had significantly more global cortical lesions than did patients with isolated cerebral tubers (17.9+/-8.9 versus 11.4+/-7.2 tubers, P = .026). Patients with cerebellar tubers were significantly older than those with isolated supratentorial tubers (11.3+/-3.4 versus 7.1+/-4.4 years, P = .005). In only four (11.8%) patients were tubers associated with focal parenchymal volume loss. The tubers in all of these cases were located in the cerebellum-indicating a significant relationship with volume loss (Pearson chi2 test, P = .017). CONCLUSION: In this series, cerebellar tubers were frequent and were always present in association with cerebral cortical tubers. They were seen in older children with a larger total number of tubers. Cerebellar tubers may be associated with focal volume loss. (+info)