Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome - A preliminary study

Background: As children with velocardiofacial syndrome (VCFS) develop, they are at increased risk for psychopathology; one third will eventually devel op schizophrenia. Because VCFS and the concomitant symptomatology result fr om a known genetic origin, the biological and behavioral characteristics of the syndrome provide an optimal framework for conceptualizing the associat ions among genes, brain development, and behavior. The purpose of this stud y was to investigate the effect of the parental origin of the 22q11.2 micro deletion on the brain development of children and adolescents with VCFS. Methods: Eighteen persons with VCFS and 18 normal control subjects were mat ched individually for age and sex. Results of DNA polymorphism analyses det ermined the parental origin of the deletion. Nine persons with VCFS had a d eletion on the maternally derived chromosome 22; 9 persons, on the paternal ly derived chromosome 22. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of gray and white matter bra in tissue. Results: Total brain volume was approximately 11% smaller in the VCFS group than in controls. Comparisons between VCFS subgroups (maternal vs paternal microdeletion 22q11.2) indicated a significant 9% volumetric difference in total volume of cerebral gray matter (volume was greater in patients with paternal microdeletion) but not cerebral white matter. Significant age-rela ted changes in gray matter were detected for subjects whose 22q11.2 deletio n was on the maternal chromosome. Conclusions: Children and adolescents with VCFS experience major alteration s in brain volumes. Significant reduction in gray matter development is att ributable to presence of 22q11.2 microdeletion on the maternal chromosome.