High rate of mosaicism in tuberous sclerosis complex

Six families with mosaicism are identified in a series of 62 unrelated fami lies with a mutation in one of the two tuberous sclerosis complex (TSC) gen es, TSC1 or TSC2. In five families, somatic mosaicism was present in a mild ly affected parent of an index patient. In one family with clinically unaff ected parents, gonadal mosaicism was detected after TSC was found in three children. The detection. of mosaicism has consequences for genetic counseli ng of the families involved, as changed risks apply to individuals with mos aicism, both siblings and parents. Clinical investigation of parents of pat ients with seemingly sporadic mutations is essential to determine their res idual chance of gonadal and/or somatic mosaicism, unless a mosaic pattern i s detected in the index patient, proving a de novo event. In our data set, the exclusion of signs of TSC in the parents of a patient with TSC reduced the chance of one of the parents to be a (mosaic) mutation carrier from 10% to 2%. In the five families with somatic mosaicism, the parent was given t he diagnosis after the diagnosis was made in the child.