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New syndromes from old: evaluation of heterogeneity and variability in syndrome definition and delineation.

In 1969, McKusick discussed the nosology of genetic disease and the importance of considering heterogeneity and variability. Those considerations are still important today in that new syndromes are being described at the rate of one or more per week. However, often a "new" syndrome actually represents variable expression of a previously described condition; at other times, a child is reported as having a variant of a previously described syndrome when in reality that child has a distinct condition. The concepts of variability and heterogeneity will be discussed in the context of recently described findings in some "old" syndromes, thus shedding new light on them.