Tuberous sclerosis complex consensus conference: Revised clinical diagnostic criteria

At the recent tuberous sclerosis complex consensus conference, the clinical diagnostic criteria for tuberous sclerosis complex were simplified and rev ised to reflect both new clinical information about tuberous sclerosis comp lex and an improved understanding of the disorder derived from molecular ge netic studies. Based on this new information, some clinical signs once rega rded as pathognomonic for tuberous sclerosis complex are now known to be le ss specific. No single sign is present in all affected patients, and there is no proof that any single clinical or radiographic sign is absolutely spe cific for tuberous sclerosis complex. Accordingly, the clinical and radiogr aphic features of tuberous sclerosis complex have now been divided into maj or and minor categories based on the apparent degree of specificity for tub erous sclerosis complex of each feature. A definitive diagnosis of tuberous sclerosis complex now requires two or more distinct types of lesions, rath er than multiple lesions of the same type in the same organ system. Althoug h diagnosis on purely clinical grounds can continue to be difficult in a fe w patients, there should be little doubt about the diagnosis for those indi viduals who fulfill these strict criteria. Couples with more than one child with tuberous sclerosis complex, no extended family history, and no clinic al features of tuberous sclerosis complex are more likely to have germline mosaicism for tuberous sclerosis than nonexpression of the mutation. Germli ne mosaicism, while fortunately rare, will not be suspected from either dia gnostic criteria or molecular testing until a couple has multiple affected children. Genetic counseling for families with one affected child should in clude a small (1% to 2%) possibility of recurrence, even for parents who ha ve no evidence of tuberous sclerosis complex after a thorough diagnostic ev aluation.