Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disease 
with a high mutation rate. It is clinically a very variable disorder and 
hamartomas can occur in many different organs. TSC shows genetic heterogeneity; 
one gene, TSC1, is on chromosome 9q34, and the second gene, TSC2, on chromosome 
16p13.3. Clinical criteria for diagnosis have been established, but diagnosis of 
patients with minimal expression of the disease can be very difficult. In 
children the phenotype is often incomplete or not fully assessable. Hence mildly 
affected subjects, at risk for severely affected offspring, may remain 
undiagnosed. The detection of (small) mutations in the tuberous sclerosis gene 
located on chromosome 16 (TSC2) has recently become possible and may be helpful 
in the diagnosis of ambiguous cases. To our knowledge, this is the first report 
of a point mutation in the TSC2 gene in a familial case of tuberous sclerosis. A 
nonsense mutation was detected in a family in which the father had only minor 
signs hinting at tuberous sclerosis. The son had multiple cardiac tumours and 
white patches, but full clinical investigation was impossible in this child. 
This case illustrates that mutation analysis can contribute to a diagnosis of 
tuberous sclerosis in families with an incomplete phenotype.