We report a boy with hypotonia, a Prader-Willi syndrome (PWS) facial phenotype, a large muscular VSD and a PDA due to maternal isodisomy for chromosome 15 with mosaic trisomy 15. At 18 months of age, his height, weight and head circumference are below the 5th %tile and his development is in the moderate mental retardation range. While our patient is unusual in having maternal isodisomy rather than the more common maternal heterodisomy, we believe, based on a review of other cases of trisomy 15 mosiacism, that his more severe PWS phenotype is due to his trisomy 15 mosaicism rather than to homozygosity for deleterious chromosome 15 genes. We propose that individuals with the PWS can have one of three similar but distinctive phenotypes depending on the etiology of their condition. Patients with paternal deletions have the typical PWS phenotype with mild to moderate mental retardation and significant behavioral problems; patients with maternal UPD have a milder physical phenotype, better cognitive function and fewer behavioral abnormalities; and patients with maternal UPD and mosaic trisomy 15 have the most severe phenotype with a high incidence of congenital heart disease, severe growth and development delays. We propose that incomplete “trisomic rescue” with residual mosaic trisomy 15 leads to this third and most “severe” Prader-Willi phenotype. Thus the phenotypic spectrum of the Prader-Willi syndrome is at least in part explainable by the varying molecular etiologies. These phenotype/genotype differences are useful both to guide the evaluation of patients with suspected PWS and to provide prognostic counseling for families.
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Wulfsberq, E., Olander, E., Stamberq, J. et al. A third Prader-Willi syndrome phenotype due to maternal uniparental disomy 15 with mosaic trisomy 15. Genet Med 2, 89 (2000). https://doi.org/10.1097/00125817-200001000-00140