Prader-Willi syndrome, deletion subtypes, and magnesium: Potential impact on clinical findings

Prader-Willi syndrome is a complex neurodevelopmental genetic imprinting disorder with severe congenital hypotonia, failure to thrive with learning and behavioral problems, and hyperphagia with obesity developing in early childhood. Those with the typical 15q11-q13 Type I deletion compared with the smaller Type II deletion have more severe neurobehavioral problems and differ by the absence of four genes in the 15q11.2 BP1-BP2 region. Two of the genes encode magnesium transporters supporting brain and neurological function and we report on magnesium levels in the two deletion groups of PWS participants. We measured baseline plasma magnesium and analyzed data from a PWS cohort with and without the Type I or Type II deletion. Significantly lower plasma magnesium levels were found in PWS participants with the larger Type I deletion and more so with females with Type I deletion compared with females having the Type II deletion, although magnesium levels remained within normal range in both subgroups. Those with PWS and the larger 15q11-q13 Type I deletion were more clinically affected than those with the smaller Type II deletion. Two of the four genes missing in those with the larger deletion code for magnesium transporters and may impact magnesium levels. Our study showed lower magnesium levels in those with the larger deletion which could contribute to neurobehavioral differences seen in the two separate 15q11-q13 deletion subtypes and in addition affect both glucose and insulin metabolism impacting comorbidities but will require more research.

Automated summary

Prader-Willi syndrome is a genetic disorder characterized by neurodevelopmental abnormalities, including low muscle tone, delayed growth and development, learning and behavioral problems, and early childhood obesity. This study found that individuals with the larger 15q11-q13 Type I deletion had more severe neurobehavioral problems compared to those with the smaller Type II deletion. Lower magnesium levels were observed in PWS participants with the larger deletion, which may contribute to the differences in neurobehavioral symptoms seen in the two deletion subtypes.