Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

Journal of Neurodevelopmental Disorders

Anita C Hokken-Koelega²  Aad van der Lugt¹  Marcus N Schmidt³  Tonya White¹  Akvile Lukoshe² 

[1] Department of Radiology, Erasmus Medical Center Rotterdam, Postbus 2040, Rotterdam 3000 CA, The Netherlands;Department of Pediatrics, Erasmus Medical Center Rotterdam – Sophia Children’s Hospital Rotterdam, Postbus 2060, Rotterdam 3000, CB, The Netherlands;Department of Child and Adolescent Psychiatry, Erasmus Medical Center Rotterdam – Sophia Children’s Hospital, Postbus 2060, Rotterdam 3000 CB, The Netherlands

关键词: Structural MRI;    Chromosome 15q11-q13;    Neurodevelopmental disorder;    Prader–Willi syndrome;   

Others  :  804630
DOI  :  10.1186/1866-1955-5-31

 received in 2013-06-17, accepted in 2013-10-02,  发布年份 2013

【 摘 要 】

Background

Prader–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.

Methods

High 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.

Results

Both 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.

Conclusions

Children 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.

【 授权许可】

   
2013 Lukoshe et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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