MOLECULAR ANALYSIS OF VELO-CARDIO-FACIAL SYNDROME PATIENTS WITH PSYCHIATRIC-DISORDERS

Velo-cardio-facial syndrome (VCFS) is characterized by conotruncal car diac defects, cleft palate, learning disabilities, and characteristic facial appearance and is associated with hemizygous deletions within 2 2q11. A newly recognized clinical feature is the presence of psychiatr ic illness in children and adults with VCFS. To ascertain the relation ship between psychiatric illness, VCFS, and chromosome 22 deletions, w e evaluated 26 VCFS patients by clinical and molecular biological meth ods. The VCFS children and adolescents were found to share a set of ps ychiatric disorders, including bipolar spectrum disorders and attentio n-deficit disorder with hyperactivity. The adult patients, >18 years o f age, were affected with bipolar spectrum disorders. Four of six adul t patients had psychotic symptoms manifested as paranoid and grandiose delusions. Loss-of-heterozygosity analysis of all 26 patients reveale d that all but 3 had a large 3-Mb common deletion. One patient had a n ested distal deletion and two did not have a detectable deletion. Soma tic cell hybrids were developed from the two patients who did not have a detectable deletion within 22q11 and were analyzed with a large num ber of sequence tagged sites. A deletion was not detected among the tw o patients at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remar kably high prevalence of bipolar spectrum disorders, in association wi th the congenital anomalies of VCFS and its occurrence among nondelete d VCFS patients, suggest a common genetic etiology.