Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis
2012; 82 (6): 552-557
Multifocal Micronodular Pneumocyte Hyperplasia: Computed Tomographic Appearance and Follow-Up in Tuberous Sclerosis Complex
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
2012; 36 (5): 518-522
Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis. A retrospective review of the clinical records and radiological images of 205 patients with tuberous sclerosis complex (TSC) was performed to evaluate the prevalence and progression of hepatic lesions; examine the association of hepatic phenotype with genotype, age, and gender; and investigate the relationships between hepatic, renal, and pulmonary involvement. Hepatic angiomyolipomas (AML), cysts, and other benign lesions were identified in 30% of the cohort, and some lesions grew significantly over time. However, no patient had clinical symptoms or complications from hepatic lesions. TSC2 patients exhibited a higher frequency of AML compared to TSC1 patients (p = 0.037), and patients with no mutation identified exhibited a higher frequency of cysts compared to TSC2 patients (p = 0.023). Age was positively correlated with frequency of hepatic involvement (p < 0.001), whereas hepatic phenotype was independent of gender. Presence of hepatic AML was associated with presence of renal AML (p = 0.001). These findings confirm a high rate of asymptomatic hepatic lesions in TSC and further characterize the TSC phenotype.
View details for DOI 10.1111/j.1399-0004.2012.01845.x
View details for Web of Science ID 000310728700010
View details for PubMedID 22251200
Genotype and cognitive phenotype of patients with tuberous sclerosis complex
EUROPEAN JOURNAL OF HUMAN GENETICS
2012; 20 (5): 510-515
To characterize pulmonary nodules in patients with tuberous sclerosis complex (TSC) using computed tomography.We retrospectively reviewed chest computed tomographic images of 73 patients with TSC (22 males and 51 females; mean ± SD age, 31.5 ± 13.2 years; range, 13.8-63.5 years).Multiple pulmonary nodules were identified in 42 (58%) of 73 patients (mean ± SD size, 6.6 ± 3.0 mm; range, 2-14 mm). Solid nodules were present in 11 (26%) of 42 patients, ground-glass nodules were present in 3 (7%) of 42 patients, and both solid and ground-glass nodules were present in 28 (67%) of 42 patients. The presence of multiple nodules was independent of sex and lymphangioleiomyomatosis. Follow-up images were available for 22 patients with multiple nodules (mean ± SD follow-up, 2.0 ± 1.1 years; range, 0.9-4.9 years), none of whom had change in nodule size or number.Most men and women with TSC have multiple pulmonary nodules, which likely represent multifocal micronodular pneumocyte hyperplasia in the absence of known predisposing factors.
View details for DOI 10.1097/RCT.0b013e318264e404
View details for Web of Science ID 000309518100003
View details for PubMedID 22992599
Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder, which affects 1 in 6000 people. About half of these patients are affected by mental retardation, which has been associated with TSC2 mutations, epilepsy severity and tuber burden. The bimodal intelligence distribution in TSC populations suggests the existence of subgroups with distinct pathophysiologies, which remain to be identified. Furthermore, it is unknown if heterozygous germline mutations in TSC2 can produce the neurocognitive phenotype of TSC independent of epilepsy and tubers. Genotype-phenotype correlations may help to determine risk profiles and select patients for targeted treatments. A retrospective chart review was performed, including a large cohort of 137 TSC patients who received intelligence assessment and genetic mutation analysis. The distribution of intellectual outcomes was investigated for selected genotypes. Genotype-neurocognitive phenotype correlations were performed and associations between specific germline mutations and intellectual outcomes were compared. Results showed that TSC1 mutations in the tuberin interaction domain were significantly associated with lower intellectual outcomes (P<0.03), which was also the case for TSC2 protein-truncating and hamartin interaction domain mutations (both P<0.05). TSC2 missense mutations and small in-frame deletions were significantly associated with higher IQ/DQs (P<0.05). Effects related to the mutation location within the TSC2 gene were found. These findings suggest that TSC2 protein-truncating mutations and small in-frame mutations are associated with distinctly different intelligence profiles, providing further evidence that different types and locations of TSC germline mutations may be associated with distinct neurocognitive phenotypes.
View details for DOI 10.1038/ejhg.2011.241
View details for Web of Science ID 000303016800015
View details for PubMedID 22189265