Age of ascertainment: an index of relative severity of cytogenetic conditions

Different cytogenetic conditions which may produce the same phenotype can be defined as phenotypically homologous. Such conditions may differ in their mean severity. It is suggested here that the age of ascertainment by cytogenetic laboratories of individuals with chromosomal abnormalities is a useful relative index of severity. Three nonmosaic cytogenetic conditions (47, + 21, 47, + 18, and 45, X) were compared with their respective mosaic homologues, using data reported by 38 laboratories participating in the New York State Chromosome Registry. For all three comparisons the mean age of ascertainment and the proportion ascertained in individuals older than 1 yr were greater for the mosaic than the nonmosaic homologues, consistent with the utility of this variable as an index of relative severity. A comparison was also undertaken between (nonmosaic) 45, X and (nonmosaic) 46, long-arm isochromosome-X forms of Turner's syndrome. Only 2% of the latter cases were ascertained under age 1 yr, compared to 25% of the former. The difference is consistent with lesser phenotypic severity of the isochromosome form of Turner's syndrome--a finding of which is independently suggested by a trend in collected heterogeneous case reports.