Implications for the Recurrence Risk in the Prader-Willi Syndrome on the Basis of Proposed Genomic Imprinting

Abstract

The Prader-Willi Syndrome (PWS) describes a complex malformation Syndrome with abnormal behavior and intellectual deficiency. About 60% of the patients show a deletion in the PW- chromosome-region 15q11q13 (PWCR) (review Ledbetter et al, 1987). In less than 5% of patients other chromosome aberrations are found, and in nearly 40% there are no cytogenetically detectable deletions. In contrast, there are deletions in PWCR reported with a normal phenotype and in Angelman Syndrome (AS) (Ledbetter et al, 1987). Murdock and Wurster-Hill (1986) list a number of proposed pathogenetic mechanisms. As the de novo-deletion- chromosome 15 derives paternally in PWS, in contrast to maternal origin in AS, a genomic imprinting mechanism was postulated. This was further supported by the surprising finding of maternal heterodisomy for PWCR in patients not showing a deletion (Nicholls et al, 1989). PWS usually occurs sporadically, yet familial recurrence is occasionally reported. It is shown that the sporadic and familial cases are consistent with a unique genetic model involving genomic imprinting.