Abstract
BackgroundPrader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses.MethodsHigh resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite.ResultsBoth children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD.ConclusionsChildren with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD.
Highlights
Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate hypothalamic, and a global, central nervous system (CNS) dysfunction
No significant differences were found in age, handedness, and gender distribution among groups, and no differences in Intelligence quotient (IQ) scores and age at start of growth hormone (GH) treatment
No differences were found in corpus callosum volume, lateral, third and fourth ventricles, and surface cerebrospinal fluid (CSF) compared with healthy controls
Summary
Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate hypothalamic, and a global, central nervous system (CNS) dysfunction. Little is known about developmental differences in brain structure in children with PWS. Our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. Prader–Willi syndrome (PWS) is a rare and poorly understood neurodevelopmental disorder that affects 1 in 15,000 to 20,000 live births [1]. Lifetime prevalence of psychotic illness in individuals with PWS is reported to be up to 60% in individuals with mUPD and up to 20% in individuals with DEL [1], which is at least 18 times higher than that in the general population [6]. Copynumber variations (CNVs) at the 15q11.2 locus were found to be associated with schizophrenia and related psychosis [8], which suggests common genetic pathways between schizophrenia, psychotic disorders, and PWS
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