Abstract
Velo-cardio-facial syndrome (VCFS) is characterized by conotruncal cardiac defects, cleft palate, learning disabilities, and characteristic facial appearance and is associated with hemizygous deletions within 22q11. A newly recognized clinical feature is the presence of psychiatric illness in children and adults with VCFS. To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, we evaluated 26 VCFS patients by clinical and molecular biological methods. The VCFS children and adolescents were found to share a set of psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients, >18 years of age, were affected with bipolar spectrum disorders. Four of six adult patients had psychotic symptoms manifested as paranoid and grandiose delusions. Loss-of-heterozygosity analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and two did not have a detectable deletion. Somatic cell hybrids were developed from the two patients who did not have a detectable deletion within 22q11 and were analyzed with a large number of sequence tagged sites. A deletion was not detected among the two patients at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggest a common genetic etiology.
Full text
PDF








Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Augusseau S., Jouk S., Jalbert P., Prieur M. DiGeorge syndrome and 22q11 rearrangements. Hum Genet. 1986 Oct;74(2):206–206. doi: 10.1007/BF00282098. [DOI] [PubMed] [Google Scholar]
- Bockman D. E., Kirby M. L. Dependence of thymus development on derivatives of the neural crest. Science. 1984 Feb 3;223(4635):498–500. doi: 10.1126/science.6606851. [DOI] [PubMed] [Google Scholar]
- Chow E. W., Bassett A. S., Weksberg R. Velo-cardio-facial syndrome and psychotic disorders: implications for psychiatric genetics. Am J Med Genet. 1994 Jun 15;54(2):107–112. doi: 10.1002/ajmg.1320540205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins J. E., Cole C. G., Smink L. J., Garrett C. L., Leversha M. A., Soderlund C. A., Maslen G. L., Everett L. A., Rice K. M., Coffey A. J. A high-density YAC contig map of human chromosome 22. Nature. 1995 Sep 28;377(6547 Suppl):367–379. doi: 10.1038/377367a0. [DOI] [PubMed] [Google Scholar]
- Couly G., Le Douarin N. M. The fate map of the cephalic neural primordium at the presomitic to the 3-somite stage in the avian embryo. Development. 1988;103 (Suppl):101–113. doi: 10.1242/dev.103.Supplement.101. [DOI] [PubMed] [Google Scholar]
- Daniels J. K., Williams N. M., Williams J., Jones L. A., Cardno A. G., Murphy K. C., Spurlock G., Riley B., Scambler P., Asherson P. No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol O-methyltransferase activity. Am J Psychiatry. 1996 Feb;153(2):268–270. doi: 10.1176/ajp.153.2.268. [DOI] [PubMed] [Google Scholar]
- Goldberg R., Motzkin B., Marion R., Scambler P. J., Shprintzen R. J. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet. 1993 Feb 1;45(3):313–319. doi: 10.1002/ajmg.1320450307. [DOI] [PubMed] [Google Scholar]
- Golding-Kushner K. J., Weller G., Shprintzen R. J. Velo-cardio-facial syndrome: language and psychological profiles. J Craniofac Genet Dev Biol. 1985;5(3):259–266. [PubMed] [Google Scholar]
- Grossman M. H., Emanuel B. S., Budarf M. L. Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1----q11.2. Genomics. 1992 Apr;12(4):822–825. doi: 10.1016/0888-7543(92)90316-k. [DOI] [PubMed] [Google Scholar]
- Halford S., Lindsay E., Nayudu M., Carey A. H., Baldini A., Scambler P. J. Low-copy-number repeat sequences flank the DiGeorge/velo-cardio-facial syndrome loci at 22q11. Hum Mol Genet. 1993 Feb;2(2):191–196. doi: 10.1093/hmg/2.2.191. [DOI] [PubMed] [Google Scholar]
- Herjanic B., Campbell W. Differentiating psychiatrically disturbed children on the basis of a structured interview. J Abnorm Child Psychol. 1977;5(2):127–134. doi: 10.1007/BF00913088. [DOI] [PubMed] [Google Scholar]
- Herjanic B., Reich W. Development of a structured psychiatric interview for children: agreement between child and parent on individual symptoms. J Abnorm Child Psychol. 1982 Sep;10(3):307–324. doi: 10.1007/BF00912324. [DOI] [PubMed] [Google Scholar]
- Jedele K. B., Michels V. V., Puga F. J., Feldt R. H. Velo-cardio-facial syndrome associated with ventricular septal defect, pulmonary atresia, and hypoplastic pulmonary arteries. Pediatrics. 1992 May;89(5 Pt 1):915–919. [PubMed] [Google Scholar]
- Karayiorgou M., Morris M. A., Morrow B., Shprintzen R. J., Goldberg R., Borrow J., Gos A., Nestadt G., Wolyniec P. S., Lasseter V. K. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7612–7616. doi: 10.1073/pnas.92.17.7612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelley R. I., Zackai E. H., Emanuel B. S., Kistenmacher M., Greenberg F., Punnett H. H. The association of the DiGeorge anomalad with partial monosomy of chromosome 22. J Pediatr. 1982 Aug;101(2):197–200. doi: 10.1016/s0022-3476(82)80116-9. [DOI] [PubMed] [Google Scholar]
- Kirby M. L., Bockman D. E. Neural crest and normal development: a new perspective. Anat Rec. 1984 May;209(1):1–6. doi: 10.1002/ar.1092090102. [DOI] [PubMed] [Google Scholar]
- Kirby M. L., Gale T. F., Stewart D. E. Neural crest cells contribute to normal aorticopulmonary septation. Science. 1983 Jun 3;220(4601):1059–1061. doi: 10.1126/science.6844926. [DOI] [PubMed] [Google Scholar]
- Kirby M. L., Waldo K. L. Neural crest and cardiovascular patterning. Circ Res. 1995 Aug;77(2):211–215. doi: 10.1161/01.res.77.2.211. [DOI] [PubMed] [Google Scholar]
- Lachman H. M., Morrow B., Shprintzen R., Veit S., Parsia S. S., Faedda G., Goldberg R., Kucherlapati R., Papolos D. F. Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. Am J Med Genet. 1996 Sep 20;67(5):468–472. doi: 10.1002/(SICI)1096-8628(19960920)67:5<468::AID-AJMG5>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
- Lindsay E. A., Greenberg F., Shaffer L. G., Shapira S. K., Scambler P. J., Baldini A. Submicroscopic deletions at 22q11.2: variability of the clinical picture and delineation of a commonly deleted region. Am J Med Genet. 1995 Mar 27;56(2):191–197. doi: 10.1002/ajmg.1320560216. [DOI] [PubMed] [Google Scholar]
- Lindsay E. A., Halford S., Wadey R., Scambler P. J., Baldini A. Molecular cytogenetic characterization of the DiGeorge syndrome region using fluorescence in situ hybridization. Genomics. 1993 Aug;17(2):403–407. doi: 10.1006/geno.1993.1339. [DOI] [PubMed] [Google Scholar]
- Morrow B., Goldberg R., Carlson C., Das Gupta R., Sirotkin H., Collins J., Dunham I., O'Donnell H., Scambler P., Shprintzen R. Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome. Am J Hum Genet. 1995 Jun;56(6):1391–1403. [PMC free article] [PubMed] [Google Scholar]
- Papolos D. F., Faedda G. L., Veit S., Goldberg R., Morrow B., Kucherlapati R., Shprintzen R. J. Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder? Am J Psychiatry. 1996 Dec;153(12):1541–1547. doi: 10.1176/ajp.153.12.1541. [DOI] [PubMed] [Google Scholar]
- Pulver A. E., Nestadt G., Goldberg R., Shprintzen R. J., Lamacz M., Wolyniec P. S., Morrow B., Karayiorgou M., Antonarakis S. E., Housman D. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis. 1994 Aug;182(8):476–478. doi: 10.1097/00005053-199408000-00010. [DOI] [PubMed] [Google Scholar]
- Rouleau G. A., Haines J. L., Bazanowski A., Colella-Crowley A., Trofatter J. A., Wexler N. S., Conneally P. M., Gusella J. F. A genetic linkage map of the long arm of human chromosome 22. Genomics. 1989 Jan;4(1):1–6. doi: 10.1016/0888-7543(89)90306-6. [DOI] [PubMed] [Google Scholar]
- Scambler P. J., Kelly D., Lindsay E., Williamson R., Goldberg R., Shprintzen R., Wilson D. I., Goodship J. A., Cross I. E., Burn J. Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus. Lancet. 1992 May 9;339(8802):1138–1139. doi: 10.1016/0140-6736(92)90734-k. [DOI] [PubMed] [Google Scholar]
- Shprintzen R. J., Goldberg R. B., Lewin M. L., Sidoti E. J., Berkman M. D., Argamaso R. V., Young D. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J. 1978 Jan;15(1):56–62. [PubMed] [Google Scholar]
- Stevens C. A., Carey J. C., Shigeoka A. O. Di George anomaly and velocardiofacial syndrome. Pediatrics. 1990 Apr;85(4):526–530. [PubMed] [Google Scholar]
- Williams J. B., Gibbon M., First M. B., Spitzer R. L., Davies M., Borus J., Howes M. J., Kane J., Pope H. G., Jr, Rounsaville B. The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability. Arch Gen Psychiatry. 1992 Aug;49(8):630–636. doi: 10.1001/archpsyc.1992.01820080038006. [DOI] [PubMed] [Google Scholar]
- Young D., Shprintzen R. J., Goldberg R. B. Cardiac malformations in the velocardiofacial syndrome. Am J Cardiol. 1980 Oct;46(4):643–648. doi: 10.1016/0002-9149(80)90515-9. [DOI] [PubMed] [Google Scholar]
- de la Chapelle A., Herva R., Koivisto M., Aula P. A deletion in chromosome 22 can cause DiGeorge syndrome. Hum Genet. 1981;57(3):253–256. doi: 10.1007/BF00278938. [DOI] [PubMed] [Google Scholar]