DOI:
Authors:
Margje Sinnema
Abstract:
Prader-Willi syndrome (PWS) is a genetic disorder caused by the absent expression of the paternal copy of maternally imprinted genes in chromosome region 15q11-13. The frequencies of different subtypes in PWS are usually given in literature as 70% deletion, 25-30% mUPD and 3-5% others (imprinting centre (IC) defects and translocations). Little is known about factors that influence the frequency of genetic subtypes in PWS. The study sample comprised 102 adults with clinically and genetically confirmed PWS, contacted through the Dutch Prader-Willi Parent Association and physicians specialized in persons with intellectual disabilities. Genetic testing showed 55 persons (54%) with a paternal deletion, 44 persons (43%) with a mUPD and 3 persons (3%) with a defect of the imprinting center. The observed distribution in our study differed from literature (70% deletion, 30% mUPD), which was statistically significant (z-score: p<0.05). This was mainly caused by a higher proportion of mUPD in the advanced age groups. Differences in maternal age and BMI of the persons with PWS could not explain the differences in distribution across the age groups. Our study population had a much broader age range, compared with other studies, because of a predominance of elderly people (40+) with PWS. In other studies, these elderly persons might have been undiagnosed and/or underreported, because of a lack of genetic diagnosis. The results underline both the need for correct genetic diagnosis in all persons with PWS and adjustment of the guidelines for preventive management in adulthood.