Multifocal micronodular pneumocyte hyperplasia: computed tomographic appearance and follow-up in tuberous sclerosis complex.

OBJECTIVE: To characterize pulmonary nodules in patients with tuberous sclerosis complex (TSC) using computed tomography. METHODS: 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). RESULTS: 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. CONCLUSIONS: Most men and women with TSC have multiple pulmonary nodules, which likely represent multifocal micronodular pneumocyte hyperplasia in the absence of known predisposing factors.

Genotype and cognitive phenotype of patients with tuberous sclerosis complex.

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.