Clinical Trial: Defining the Brain Phenotype of Children With Williams Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Defining the Brain Phenotype of Children With Williams Syndrome

Brief Summary:

Background:

- Little is known about how the brain changes during childhood and adolescence, how genes affect this process, or how the brains of people with Williams syndrome change during this period. Genetic features of Williams syndrome affect the brain s development, but the details of this process have not been studied over time. Researchers are interested in using magnetic resonance imaging to study how the brain changes in healthy children and children with Williams syndrome and related genetic disorders.

Objectives:

- To study developmental changes in the brains of healthy children and children who have been diagnosed with Williams syndrome or a related genetic disorder.

Eligibility:

• Healthy children and adolescents between 5 and 17 years of age.
• Children and adolescents between 5 and 17 years of age who have been diagnosed with Williams syndrome or genetic characteristics that overlap with Williams syndrome.

Design:

• Participants will have a brief physical examination and tests of memory, attention, concentration, and thinking. Parents will be asked about their child s personality, behavior characteristics, and social interaction and communication skills.
• Both participants and their parents may be asked to complete additional questionnaires or take various tests as required for the study.
• Participants will have approximately 10 hours of magnetic resonance imaging (MRI) scanning, usually over 4 to 5
  

  Detailed Summary:

  Williams syndrome (WS) is a rare disorder caused by hemizygous microdeletion of approximately 1.6 megabases on chromosomal band 7q11.23, typically by spontaneous mutation. The disorder is characterized by a collection of unique neuropsychiatric manifestations, including marked visuospatial construction deficits and hypersociability. Because the genes involved in WS are known, the study of neural mechanisms in WS affords a privileged setting for investigating genetic influences on complex brain functions in a bottom-up way.

  Previous neuroimaging studies of adults with WS resulted in a clear delineation of the WS brain phenotype. Underlying the syndrome s cognitive hallmark, visuospatial construction impairment, is a neurostructural anomaly (decreased gray matter volume) and adjacent abnormal neural function in the parietal sulcus region of the dorsal visual processing stream. Subtle structural hippocampal alterations, along with abnormalities in regional cerebral blood flow, neurofunctional activation, and N-acetyl aspartate concentration also contribute to the visuospatial phenotype. Underlying the syndrome s social cognition features are structural and functional abnormalities in the orbitofrontal cortex, an important affect and social regulatory region that participates in a fronto-amygdala regulatory network found to be dysfunctional in WS.

  The findings in adult WS patients have created a paradigm for identifying brain phenotypes linked to specific genes and for guiding research aimed at understanding the mechanism by which gene effects are translated in the brain to clinical phenomena. However, it is clear that the cognitive and behavioral disturbances in WS emerge over the course of childhood and adolescence from a complex interplay of altered neural systems, which must be studied from a developmental and translationa
  Sponsor: National Institute of Mental Health (NIMH)
  

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  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: May 27, 2010
  Date Started: April 30, 2010
  Date Completion:
  Last Updated: April 20, 2017
  Last Verified: December 13, 2016