Diagnosis of Tuberous Sclerosis Complex

E. Steve Roach MD; Steven P. Sparagana MD


J Child Neurol. 2004;19(9):643-649. 

In This Article

Diagnosis of Tuberous Sclerosis Complex by DNA Analysis

Testing for TSC1 and TSC2 mutations has been available from Athena Diagnostics, Inc. (Worcester, MA) since 2002. Confirmatory testing for tuberous sclerosis complex is helpful in individuals who fail to meet the criteria for definite tuberous sclerosis complex and to improve genetic counseling. Prenatal genetic testing for tuberous sclerosis complex is also possible when there is a defined tuberous sclerosis complex mutation in a specific family. Preimplantation genetic diagnosis is a method of determining the genetic characteristics of an embryo created by in vitro fertilization. Although preimplantation genetic diagnosis is feasible for tuberous sclerosis complex, its use is not widespread.[25,26,27]

Several issues limit the usefulness of confirmatory testing for tuberous sclerosis complex, beginning with the fact that most patients develop the disorder via a spontaneous mutation. And although there are few false-positive tests, as much as 15 to 20% of the time the test fails to demonstrate a disease-causing mutation. Nevertheless, confirmatory testing in an individual who already fulfills the diagnostic criteria for definite disease can help identify a mutation that can then be sought in other family members or for subsequent prenatal diagnosis.

Somatic and germline mosaicism also complicate confirmatory testing for tuberous sclerosis complex. Somatic mosaicism occurs when an individual has a mutation in some, but not all, cells and tissues. Such an individual often has milder manifestations of tuberous sclerosis complex or manifestations limited to a single organ system but can have more severely affected progeny.[18] Germline mosaicism occurs when an individual carries a mutation only in the germ cells and has no other signs or symptoms of the given disease. Germline mosaicism probably accounts for about 2% of the patients,[29] making genetic counseling more difficult even when a specific mutation has been identified. Hence, a conservative recurrence risk for seemingly unaffected couples with a single affected child, even when they have no demonstrable tuberous sclerosis complex mutation, is 2%.

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