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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tuberous sclerosis complex is a genetic multisystem disease characterized by hamartic development of many organs, most notably the brain, heart, kidneys, lungs, and skin. This autosomic dominant disorder results from mutations in one of two genes, TSC1 and TSC2, coding for hamartin and tuberin, respectively. The hamartin-tuberin complex inhibits the mammalian target of rapamycin pathway, which controls cell growth and proliferation. The clinical presentation is highly variable and most features of tuberous sclerosis become evident only in childhood after the child is several years of age, limiting their usefulness for early diagnosis. The aim of this article is to define the pediatric clinical manifestations of tuberous sclerosis in correlation with patient age. Sometimes, a prenatal diagnosis can be made based on fetal ultrasound and MRI, which show cardiac and brain lesions. However, newborns are most often asymptomatic. In the 1st year, seizures are the most common symptoms, with a high incidence of infantile spasms. In children between 2 and 10 years of age, neurological symptoms are the most frequent with epilepsy, mental retardation, and autism, but extraneurological manifestations can be diagnosed. In adolescents, most features of tuberous sclerosis become evident and renal and pulmonary manifestations must be sought. The knowledge of age-dependent clinical features of tuberous sclerosis can provide an earlier diagnosis and improve the management of these patients with a special role for multidisciplinary consultation.
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PMID:[Characteristics of tuberous sclerosis in children]. 2070 8

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.
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PMID:Genotype and cognitive phenotype of patients with tuberous sclerosis complex. 2218 65

Tuberous sclerosis complex is a genetic disorder characterized by the formation of nonmalignant hamartomas in the brain, heart, skin, kidney, lung, and other organs. It is associated with autism, epilepsy, and other neurocognitive and behavioral disabilities. Wide phenotypic variation occurs in disease severity and natural course: some patients demonstrate minimal effects, e.g., skin changes; others manifest profound seizures and mental retardation. Tuberous sclerosis complex is caused by mutations in either the tuberous sclerosis complex 1 or 2 gene (coding for hamartin and tuberin, respectively). The tuberous sclerosis complex 1/tuberous sclerosis complex 2 protein dimer complex is a crucial inhibitory element in the mammalian target of rapamycin pathway, regulating cell growth and proliferation. Until recently, few options existed, other than surgery, for treating symptoms of tuberous sclerosis complex related to the growth of hamartomas. Increased understanding of the genetic cause of the disease and underlying dysregulation of the mammalian target of rapamycin pathway has led to clinical trials of mammalian target of rapamycin inhibitors, including sirolimus and everolimus. This review gives an overview of tuberous sclerosis complex and its molecular causes, and summarizes results from recent clinical trials of mammalian target of rapamycin inhibitors in patients with the disease.
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PMID:Emerging treatments in the management of tuberous sclerosis complex. 2252 Mar 46


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