Role of mutational analysis in diagnosis of tuberous sclerosis complex

Abstract

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.

Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model

“…Thus, although mice haploinsufficient for the Tsc genes have been utilized as models of autism41920, occurrence of spontaneous seizures in Tsc1 +/− and Tsc2 +/− rodents have not been reported previously46. It is possible that early spontaneous epileptic activity in Tsc1 +/− heterozygous knockout mice has been overlooked because of the strictly limited age window (<P19) found in our study.…”

The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management

“…Since mutations can be indentified in the majority of cases of TS, genetic testing can make a valuable contribution to the diagnostic evaluation,11 particularly in younger children who are less likely to fulfil the clinical criteria for a definite diagnosis. Clinicians in this study seldom used genetic testing as part of the diagnostic evaluation and this investigation was usually carried out later to address genetic issues in the family.…”

Recognition of Tuberous Sclerosis in Adult Women: Delayed Presentation With Life-Threatening Consequences

“…Most of our patients had not been tested for mutations in TSC1 or TSC2 , but DNA testing is now commercially available and may permit earlier diagnosis, even before patients meet clinical diagnostic criteria (5). A negative genetic test result does not exclude the possibility of TSC, because no mutation is identified in approximately 15% of patients who fulfill diagnostic criteria for TSC (39).…”