RESUMEN
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a prominent finding in the setting of tuberous sclerosis complex (TSC). OBJECTIVE: The present study was designed to compare cystic lung changes consistent with LAM in patients with a TSC1 disease-causing mutation, TSC2 disease-causing mutation, or no mutation identified (NMI). METHODS AND RESULTS: We conducted a retrospective review of the chest computed tomography (CT) of 45 female and 20 male patients with TSC and found cysts consistent with LAM in 22 (49%) women and two (10%) men. In the female population, changes consistent with LAM were observed in six of 15 (40%) patients with TSC1, 11 of 23 (48%) with TSC2, and five of seven (71%) with NMI. While the predominant size of cysts did not differ across these three groups, TSC2 women with LAM had a significantly greater number of cysts than did TSC1 patients (p = 0.010). CONCLUSIONS: These findings suggest a higher rate of LAM in TSC1 than previously recognised, as well as a fundamental difference in CT presentation between TSC1 and TSC2.
Asunto(s)
Linfangioleiomiomatosis/genética , Mutación , Esclerosis Tuberosa/genética , Proteínas Supresoras de Tumor/genética , Adulto , Distribución de Chi-Cuadrado , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Humanos , Linfangioleiomiomatosis/diagnóstico por imagen , Masculino , Radiografía Torácica , Estudios Retrospectivos , Estadísticas no Paramétricas , Esclerosis Tuberosa/diagnóstico por imagen , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteína 2 del Complejo de la Esclerosis TuberosaRESUMEN
We describe three cases in whom identification of a disease-causing mutation in the TSC1 or TSC2 gene preceded the appearance or detection of symptoms sufficient for a clinical diagnosis of tuberous sclerosis complex (TSC). We suggest that genetic testing be given a more prominent role in the evaluation of individuals with a family history of TSC or symptoms suggestive of TSC and propose that diagnostic criteria be revised to include genetic testing.
Asunto(s)
Análisis Mutacional de ADN , Esclerosis Tuberosa/diagnóstico , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos , Esclerosis Tuberosa/patología , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteína 2 del Complejo de la Esclerosis Tuberosa , Proteínas Supresoras de Tumor/genéticaRESUMEN
OBJECTIVE: The purpose of this study was to assess the prevalence of and to identify epidemiologic, genetic, electrophysiologic, and neuroanatomic risk factors for autism spectrum disorders (ASD) in a cohort of patients with tuberous sclerosis complex (TSC). METHODS: A total of 103 patients with TSC were evaluated for ASD. A retrospective review of patients' records was performed, including mutational analysis. EEG reports were analyzed for the presence of ictal and interictal epileptiform features. Brain MRI scans were evaluated for TSC neuropathology, including tuber burden. RESULTS: Of the 103 patients with TSC, 40%were diagnosed with an ASD. On univariate analysis, patients with ASD were less likely to have mutations in the TSC1 gene. Patients with ASD also had an earlier age at seizure onset and more frequent seizures. On EEG, those with ASD had a significantly greater amount of interictal epileptiform features in the left temporal lobe only. On MRI, there were no differences in the regional distribution of tuber burden, although those with TSC2 and ASD had a higher prevalence of cyst-like tubers. CONCLUSIONS: The development of ASD in TSC is not well understood. Given our findings, ASD may be associated with persistent seizure activity early in development in particular brain regions, such as those responsible for social perception and communication in the left temporal lobe. The presence of cyst-like tubers on MRI could provide a structural basis or marker for ASD pathology in TSC, although studies assessing their effect on cortical function are needed.