The syndromes of Sotos and Weaver are paradigmatic of the daily nosologic 
difficulties faced by clinical geneticists attempting to diagnose and counsel, 
and to give accurate prognoses in cases of extensive phenotypic overlap between 
molecularly undefined entities. Vertebrate development is constrained into only 
very few final or common developmental paths; therefore, no developmental 
anomaly seen in humans is unique to ("pathognomonic" of) one syndrome. Thus, it 
is not surprising that prenatal overgrowth occurs in several syndromes, 
including the Sotos and Weaver syndromes. Are they sufficiently different in 
other respects to allow the postulation of locus (rather than allele) 
heterogeneity? Phenotypic data in both conditions are biased because of 
ascertainment of propositi, and the apparent differences between them may be 
entirely artificial as they were between the G and BBB syndromes. On the other 
hand, the Sotos syndrome may be a cancer syndrome, the Weaver syndrome not 
(though a neuroblastoma was reported in the latter); in the former there is also 
remarkably advanced dental maturation rarely commented on in the latter. In 
Weaver syndrome there are more conspicuous contractures and a facial appearance 
that experts find convincingly different from that of Sotos individuals. 
Nevertheless, the hypothesis of locus heterogeneity is testable; at the moment 
we are inclined to favor the hypothesis of allele heterogeneity. An 
international effort is required to map, isolate, and sequence the causal gene 
or genes.