Prader-Willi syndrome is a multisystem disorder due to absence of paternally expressed imprinted genes at 15q11.2-q13. Diminished bone mineral density (BMD) and osteoporosis are common in PWS individuals, especially in adolescence and adulthood. The reasons for the increased prevalence of osteoporosis in PWS are not totally clear, but decreased production of sex and growth hormones and hypotonia most likely contribute to the increased tendency to develop osteoporosis.
The osteoporotic process may begin earlier than adolescence due to other hormonal abnormalities which affect bone mineral density. Vitamin D (1,25(OH)2D3) receptors (VDR) have an important physiological effects such as calcium transport and cell growth and differentiation and VDR polymorphisms have been shown to be associated with risk factors for osteoporosis among the general population as well as in other diseases. A recent study showed that VDR polymorphism may be an independently sorting modifier in the prediction of BMD and bone involvement in Gaucher disease. It is possible that also in PWS, genetic factors such as VDR polymorphism are important in determining the risk of diminished BMD.
Osteoporosis is diagnosed with a dual-energy X-ray absorptiometry (DEXA) scan which is a painless, lowdose X-ray procedure. We plan to examine all 102 individuals with genetically confirmed PWS in Israel who are treated in the National PWS Multidisciplinary Clinic and are above the age of 3 years. All study participants will undergo DEXA scan, physical examination and blood tests including Vitamin D levels and screening for VDR polymorphisms.
If osteopenia/osteoporosis is diagnosed, treatment will be tailored to the individual's clinical, genotype and laboratory findings. Better understanding of the role of VDR polymorphism in development of osteoporosis may allow for more specific and individualized treatment.