22q11.2 deletion syndrome in diverse populations

Abstract

22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P < 0.05). However, when Africans were removed from analysis, six additional clinical features were found to be independent of ethnicity (P ≥ 0.05). Using facial analysis technology, we compared 156 Caucasians, Africans, Asians, and Latin American individuals with 22q11.2 DS with 156 age and gender matched controls and found that sensitivity and specificity were greater than 96% for all populations. In summary, we present the varied findings from global populations with 22q11.2 DS and demonstrate how facial analysis technology can assist clinicians in making accurate 22q11.2 DS diagnoses. This work will assist in earlier detection and in increasing recognition of 22q11.2 DS throughout the world.

Keywords: 22q11.2 Deletion syndrome; DiGeorge syndrome; Velocardiofacial Syndrome; diverse populations; facial analysis technology.

Figure 1

Facial landmarks on a 22q11.2 deletion syndrome patient. Inner facial landmarks are represented in red, while external landmarks are represented in blue. Blue lines indicate the calculated distances. Green circles represent the corners of the calculated angles. Texture features are extracted only from the inner facial landmarks.

Figure 2

Frontal and lateral facial profiles of individuals of African descent with 22q11.2 deletion syndrome. Gender, age, and country of origin found in Supplementary Table I. ^aIndividual previously published in Uwineza et al., 2014 ^bReprinted from De Decker et al., 2016 ^cVeerapandiyan et al., 2011

Figure 3

Frontal and lateral facial profiles of Asian individuals with 22q11.2 deletion syndrome. Gender, age, and country of origin found in Supplementary Table I. ^dIndividual previously published in Liu et al., 2014

Figure 4

Frontal and lateral facial profiles of Latin Americans with 22q11.2 deletion syndrome. Gender, age, and country of origin found in Supplementary Table I. ^eReprinted from Grassi et al., 2014

Figure 5

Hand findings. Image numbers correspond with Supplementary Table I. ^dIndividual previously published in Liu et al., 2014

Figure 6

Foot findings. Image numbers correspond with Supplementary Table I. ^dIndividual previously published in Liu et al., 2014