Children with Prader-Willi at increased risk for congenital defects

Jennifer Miller, MD

Torrado et al reported the prevalence of congenital defects in 180 patients with Prader-Willi syndrome. Congenital defects included in this retrospective study consisted of heart defects, renoureteral malformations, vertebral abnormalities, hip dysplasia, clubfoot and agenesis/hypoplasia of the corpus callosum. The authors found that 22% of patients with Prader-Willi syndrome presented with one of these congenital defects, which is a 5.4 to 18.7 higher risk than is seen in the general population.They recommend that physicians screen patients with Prader-Willi syndrome for the presence of these congenital defects when the diagnosis is made.

Although this was a retrospective study, it included a large number of patients and provides novel information about congenital defects in children with Prader-Willi syndrome. Prevalence of the conditions evaluated in individuals with Prader-Willi syndrome was compared with population registries. Interestingly, 82.5% of these birth defects were detected before the diagnosis of Prader-Willi syndrome being confirmed, and 90% were detected within the first 2 years of life. Therefore, many congenital defects are likely to be found during the evaluation for neonatal hypotonia and poor feeding, which are the presenting symptoms of Prader-Willi syndrome in infancy. However, the findings of this study indicate that if evaluations for congenital defects have not been done before diagnosis, they should be done at the time of diagnosis. The authors recommend that infants with Prader-Willi syndrome have abdominal, renal and hip ultrasound, as well as cardiologic evaluation, spine X-ray, and brain imaging (cerebral ultrasound for infants).

Overall this study provides interesting data on the prevalence of congenital birth defects in individuals with Prader-Willi syndrome, but these findings need to be replicated in other large series of patients with Prader-Willi syndrome followed around the world. International registries are being created by the parent support organizations, which will allow for characterization of congenital defects in a larger, international population of individuals with Prader-Willi syndrome.

Shawn E. McCandless, MD

This interesting study confirms something that providers who treat children with Prader-Willi syndrome have recognized, which is that there are many individual birth defects that we recognize as occurring more commonly. I don't think these findings will come as a surprise to those providers. However, I think the documentation of the magnitude of the effect is maybe a little surprising.

In general, genetic syndromes predispose to a wide variety of birth defects, and this is widely recognized. Studies like this really begin to quantitate the magnitude of that effect, and it really raises some fundamental questions about the underlying mechanisms for birth defects, especially with Prader-Willi syndrome. We know a lot about the molecular findings in these children, but we really don't have a good handle on the molecular mechanisms — the particular genetic changes — and why and how they cause the specific findings of Prader-Willi syndrome.

This study shows us that there is a lot more going on in the developing embryo than we knew before due to Prader-Willi syndrome. Whatever the changes are in this syndrome, they are having fundamental effects on just about every organ system during embryotic development, and that is not something that we've recognized in the past as well as we might have. In the past, we've tended to think of Prader-Willi syndrome being primarily a hypothalamic abnormality that then leads to downstream endocrine and neuroendocrine signaling abnormalities, which lead to the specific defects. This study suggests that there may be much more fundamental effects of whatever the underlying processes in Prader-Willi syndrome are that effect the development of a variety of organ systems that we didn't necessarily think of as being Prader-Willi syndrome.