Health Problems in Adults with Prader–Willi Syndrome of Different Genetic Subtypes: Cohort Study, Meta-Analysis and Review of the Literature

Context: Prader-Willi syndrome (PWS) is a complex rare genetic disorder caused by loss of expression of paternally expressed genes on chromosome 15q11.2-q13. The most common underlying genotypes are paternal deletion (DEL) and maternal uniparental disomy (mUPD). DELs can be subdivided in type 1 (DEL-1) and (smaller) type 2 deletions (DEL-2). Most research has focused on behavioral, cognitive and psychological differences between the different genotypes. However, little is known about physical health problems in relation to genetic subtype.
Objective: To compare physical health problems and other clinical features among adults with PWS caused by DEL-1, DEL-2 and mUPD.
Design: Cross-sectional.
Setting: Outpatient clinic.
Patients or other participants: Adults with genetically confirmed PWS.
Main outcome measure: Prevalence of physical and psychiatric complaints, symptoms and diagnoses.
Results: Twenty-eight adults had an mUPD and 65 a DEL (12 DEL-1, 27 DEL-2). A metaanalysis, including our own data, showed that BMI was 2.79 kg/m2 64 higher in adults with a DEL (P = .001). There were no significant differences between DEL-1 and DEL-2. Scoliosis was more prevalent among adults with a DEL (80% vs. 58%; P = .04). Psychotic episodes were significantly more prevalent among adults with an mUPD (44% vs. 9%; P < .001).
Conclusions: Apart from scoliosis and BMI, there were no significant differences in physical health outcomes between the genetic subtypes. The differences in health problems therefore mainly apply to the psychological domain. Especially psychotic episodes were more frequent in adults with an mUPD.