Delayed diagnosis in patients with Prader-Willi syndrome due to maternal uniparental disomy 15.

Prader-Willi syndrome (PWS) results from absence of the normally active paternally inherited genes on proximal 15q, due to del(15)(q11q13) or by maternal uniparental disomy (UPD) 15 in most cases. In addition to a higher frequency of hypopigmentation among deletion patients, minor phenotypic differences between deletion and UPD patients have recently been reported, including lower birth weight in the deletion group, shorter birth length in males with UPD, and shorter course of gavage feeding and later onset of hyperphagia in females with UPD. We previously reported that those with UPD had a less "typical" facial appearance, and they less often had skin picking, skill with puzzles, and high pain threshold. There were no children younger than 3.5 years of age in the UPD group, in contrast to several of them in the deletion group, suggesting a possible diagnostic delay in the UPD group. To assess this possibility and seek reasons for it, we reviewed the charts of 60 PWS patients with complete molecular testing. Mean age at diagnosis of patients with UPD was significantly higher than in the deletion group. Mean percentiles of birth weights and lengths of patients with UPD were significantly lower than in those with deletion. Mean duration of gestation, mean duration of gavage feeding, and mean age at onset of hyperphagia did not differ significantly between groups. Delay in the diagnosis of patients with UPD, which may influence the management and impact of the disorder, might be explained by a lower frequency of typical facial anomalies in this group.