Brain Size and Cerebellar Volume in Individuals with Prader-Willi Syndrome: What Factors may Influence Brain Development and IQ

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Jennifer L Miller, Krista Schwenk, Michelle Long, Stephen Towler, Daniel J Driscoll, Christiana Leonard

University of Florida College of Medicine and College of Education

Both total brain volume and the cerebellum have been found to correlate with cognition. In a previous study we noted that individuals with Prader-Willi syndrome (PWS) and those with early-onset morbid obesity (EMO) of unknown etiology had lower cognitive function that their normal weight siblings. Therefore, we hypothesized that individuals with PWS and EMO would have smaller brain volume and cerebellar volume than normal weight controls.

We measured total brain volume and total cerebellar volume using three-dimensional MRI images in 18 individuals with PWS (8 females/10 males), 19 individuals with EMO (13 females/6 males), and 24 normal weight control siblings from both groups (14 females/10 males), all of whom were ages 4-30 years. These measurements were obtained by two independent raters who were blinded to age, gender, and diagnosis of the subjects.

We found that the total brain volumes were similar in all groups (p=0.4), but the cerebellum (p=0.004) and the cerebellar/cerebral volume ratio was smaller in both individuals with EMO and PWS compared to controls (p=0.03). There was no difference in cerebellum/cerebral volume ratio between individuals with PWS and individuals with EMO, or between the two major sub-types of PWS (deletion vs. maternal uniparental disomy). General intellectual ability in these individuals was: PWS 65 ± 15; EMO 81 ± 12; and Controls 112 ± 7.

Decreased cerebellar/cerebral volume ratio in both individuals with EMO and PWS, along with the findings of decreased cognitive scores in both of these groups, compared to controls further suggests that the cerebellum plays a role in overall cognitive functioning. Additionally, since the only commonality between the individuals with PWS and those with EMO is the development of obesity early in life, our findings suggest that early-onset childhood obesity may result in decrease of cerebellar volume with concommitent decrease in cognitive function.