Clinical and cytogenetic studies of the Prader-Willi syndrome: evidence of phenotype-karyotype correlation.

Twenty-seven patients with the presumed diagnosis of Prader-Willi syndrome (PWS) were studied clinically and cytogenetically. The patients were classified into three study groups on the basis of their clinical pictures: group 1 with 12 children meeting the strict diagnostic criteria for PWS; group 2 with nine floppy infants and young children, aged 3 years or less, without obesity and hyperphagia; and group 3 with six older children in whom some characteristic features of the syndrome were absent. High-resolution GTG banding of prometaphase chromosomes revealed del(15)(q11.1;q12) in eleven and t(15;15)(qter----p11.2::q12----qter) in one of the twelve group 1 patients. In group 2, four patients had del(15)(q11.1; q12), one had t(15;15)(qter----p11.1::q13----qter), and the remaining four had normal karyotypes. The deleted segment common to the 17 patients with the chromosome aberrations was confined to subband 15q11.2. On the other hand, all six group 3 patients had normal karyotypes. These findings indicated that when strictly defined PWS is absolutely correlated with chromosome 15 aberrations, i.e., there is a positive phenotype-karyotype correlation, and that the aberrations are etiologically related to the syndrome. Parental origin of the deleted chromosome was determined in seven patients, with QFQ-heteromorphisms being used as hereditary markers. The deleted chromosome originated from the paternal chromosome 15 in six patients and from the maternal 15 in one.