Am] Psychiatry 153:12, December 1996 1541 Bipolar Spectrum Disorders in Patients Diagnosed With Velo-Cardio-Facial Syndrome: Does a Hemizygous Deletion of Chromosome 22q1 1 Result in Bipolar Affective Disorder? Demitri F. Papolos, M.D., Gianni L. Faedda, M.D., Sabine Veit, M.D., Rosalie Goldberg, M.S., Bernice Morrow, Ph.D., Raju Kucherlapati, Ph.D., and Robert J. Shprintzen, Ph.D. Objective: The purpose of this study was to conduct a systematic assessment of psychiatric illness in patients diagnosed with velo-cardio-facial syndrome, a genetic syndrome that involves over 40 somatic anomalies, learning disabilities, and behavioral disorders and is associated with a microdeletion on chromosome 22q1 1 . Method: Subjects were referred for psychiatric diagnos- tic evaluation without regard to age or previous psychiatric history. In order to establish DSM- III-R consensus clinical diagnoses for patients who ranged in age from 5 to 34 years, the I)iag- nostic Interview for Children and Adolescents-Revised or the Structured Clinical Interview for DSM-III-R (SCID) was used. A review ofavailable medicaland psychiatric records and a clinical interview performed by two research psychiatrists to validate specific symptoms and syndromes reported in the Diagnostic Interview for Children and Adolescents-Revised and the SCID were used to elucidate the chronological appearance and duration of symptoms. Results: Sixty-four percent (N= I6 of 25) of this unselected series of patients with velo-cardio-facial syndrome tizet DSM-II1-R criteria for a spectrum of bipolar disorders with full syndromal onset in late child- hood or early adolescence (mean age at onset=12 years, SD=3). in addition, 20% (N=5) met DSM-III-R criteria for attention deficit hyperactivity disorder (ADHD), while 1 6% (N=4) met criteria for attention deficit disorder without hyperactivity. I,: coiztrast to previous reports of a high prevalence of schizophrenia, none of the patients was diagnosed with schizophrenia, azid only four had psychotic symptoms during a phase oftheir illness, all in their 20s or 30s. Conch- sions: Given that the prevalence of bipolar disorder in the general population is estimated to be I .5% and that the average age at onset is 24, these findings support an uzzusually strozg asso- ciation between velo-cardio-facial syndrome and early-onset bipolar disorder and suggest that a gene deleted at the 22q1 1 chromosomal locus may be involved in its pathogenesis. If cozz firmed, these findings may provide a new and fruitful line of investigation into the molecular basis of bipolar spectrum disorders. (AmJ Psychiatry 1996; 153:1541-1547) Received Sept. 25, 1995; revisions received March 20 andjune 12, 1996; accepted July 12, 1996. From the Department of Psychiatry, Program in Behavioral Genetics, Department of Molecular Genetics, Albert Einstein College of Medicine of Yeshiva University and the Center for Craniofacial Disorders, Montefiore Medical Center. Ad- dress reprint requests to Dr. Papolos, Departiiient of Psychiatry, Pro- gram of Behavioral Genetics, Albert Einstein College of Medicine of Yeshiva University/Montefiore Medical Center, 1300 Morris Park Ave., Bronx,NY 10461. Supported in part by NIMH grant MH-00873 (Dr. Papolos), NIH grant HD-31601 from the National Institute ofChild Health and Hu- man Development (Dr. Kucherlapati), and a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression (Dr. Morrow). The authors thank Dr. Ross J. Baldessarini for his conirnents on the manuscript and Ms. Shelly Wolfson for assisting with the administra- tion of the Diagnostic Interview for Children and Adolescents-Re- vised interviews. V elo-cardio-facial syndrome, also known as Shprint- zen syndrome, is a relatively common multiple anomaly disorder estimated to affect between 1 in 3,000 and I in 5,000 individuals; it may he as common as Down’s syndrome (R.J. Shprintzen, unpublished work, 1995; 1). The original presenting symptoms that called attention to its pattern were the association of hypernasal speech (usually with cleft palate), cardiac anomalies, learning disabilities, and a characteristic fa- cial appearance that included a long face, large nose with large tip and high nasal root, small ears with over- folded helices, narrow, “squinting” eyes, and flat cx- pression (2). Veio-cardio-facial syndrome is a complex disorder that affects a number of tissues and organ sys- tems, many of which are derived from neural crest cells