A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population.

OBJECTIVES: Although several studies describe the 22q11.2 deletion, population-based data are scant. Such data are needed to evaluate properly the impact, distribution, and clinical presentation of the deletion in the population. Our goals were to assess the population-based birth prevalence of the 22q11.2 deletion and its associated phenotype and its impact on the occurrence of heart defects.

METHODS: We evaluated data on infants who were born from 1994 through 1999 to women who resided in metropolitan Atlanta. We matched records from the Metropolitan Atlanta Congenital Defects Program (a population-based registry with active case ascertainment), the Sibley Heart Center at Children's Healthcare of Atlanta, and the Division of Medical Genetics at Emory University. We used birth certificate data for the denominators of the rates.

RESULTS: We identified 43 children with laboratory-confirmed 22q11.2 deletion among 255 849 births. The overall prevalence was 1 in 5950 births (95% confidence interval: 1 in 4417 to 1 in 8224 births). The prevalence was between 1 in 6000 and 1 in 6500 among whites, blacks, and Asians and 1 in 3800 among Hispanics. Most affected children (81%) had a heart defect, and many (1 in 3) had major extracardiac defects (other than velopalatal anomalies), including anomalies of the central nervous system. Overall, the deletion contributed to at least 1 of every 68 cases of major heart defects identified in the total birth cohort and, in particular, to 1 of every 2 cases diagnosed with interrupted aortic arch type B, 1 of every 5 with truncus arteriosus, and 1 of every 8 with tetralogy of Fallot.

CONCLUSIONS: The 22q11.2 deletion was common in this birth population. The clinical phenotype included a wide and variable spectrum of major cardiac and extracardiac anomalies. From these population-based data, one can estimate that at least 700 affected infants are born annually in the United States. Population-based estimates such as these should be useful to medical professionals and policy makers in planning for the optimal care of people with the 22q11.2 deletion.