Third Prader-Willi syndrome phenotype due to maternal uniparental disomy 15 with mosaic trisomy 15.
We report on a boy with mosaicism for trisomy 15 and Prader-Willi syndrome (PWS) due to maternal isodisomy for chromosome 15. His phenotype is consistent with PWS and trisomy 15 mosaicism. Although our patient is unusual in having maternal isodisomy rather than the more common maternal heterodisomy, we think 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 PWS have one of three similar but distinctive phenotypes depending on the cause of their condition. Patients with paternal deletions have the typical PWS phenotype, patients with maternal UPD have a slightly milder phenotype with better cognitive function, and those with maternal UPD and mosaic trisomy 15 have the most severe phenotype with a high incidence of congenital heart disease. These phenotype-genotype differences are useful to guide the work-up of patients with suspected PWS and to provide prognostic counseling for families.
Olander
E
E
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, USA. erikaolander@yahoo.com
Stamberg
J
J
Steinberg
L
L
Wulfsberg
E A
EA
D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15; D004374:Ductus Arteriosus, Patent / Q000235:genetics; D005260:Female; D005838:Genotype; D006344:Heart Septal Defects, Atrial / Q000235:genetics; D006345:Heart Septal Defects, Ventricular / Q000235:genetics; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D008297:Male; D009035:Mothers; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D014314:Trisomy