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.

Beckwith–Wiedemann syndrome in diverse populations

“…This difference in phenotype may be due to a combination of recognition bias and referral bias. Recognition bias is due to the possibility that facial features are distinct in different populations as has been demonstrated in other syndromes (Kruszka, Addissie, et al, ; Kruszka, Porras, Addissie, et al, ; Kruszka, Porras, Sobering, et al, ; Kruszka et al, ) and as such the facial gestalt in BWS may be under‐diagnosed in non‐Caucasian groups. Secondly, referral bias may exist in that non‐Caucasian patients with BWS may be less frequently referred to a tertiary care center due to socioeconomic stratification and/or other barriers to care and follow‐up, resulting in only the extreme cases such as hyperinsulinism being referred.…”

“…The importance of diversity in malformation syndromes has recently arisen as an important topic for both diagnosis and management of patients. Studies using facial analysis technology have revealed subtle differences in the facial appearance between racial groups in patients with Down syndrome, 22q syndrome, Noonan syndrome, and Williams–Beuren syndrome (Kruszka, Addissie, et al, ; Kruszka, Porras, Addissie, et al, ; Kruszka, Porras, Sobering, et al, ; Kruszka et al, ).…”

Silver Russel syndrome in an aboriginal patient from Australia

“…We describe a novel IGF2 splice site pathogenic variant in a child with SRS, the first to be described in an Australian Aboriginal girl adding to the body of literature on the phenotype associated with IGF2 pathogenic variants. For global health equity, it is critical to report the phenotype of rare conditions within and between diverse populations (Kruszka et al, ). We expand on the phenotype by displaying the facial photographs (Figure ), to assist in diagnosing further Aboriginal and Non‐Aboriginal children via raising awareness of the clinical cues important for prompting consideration of further diagnostic investigations (Wakeling et al, ).…”

The genetic workup for structural congenital heart disease

“…Likewise, adults with CHD should undergo an equivalent evaluation by an adult congenital heart disease specialist or medical geneticist. Facial analysis technology is becoming a useful tool to assist both the geneticists and nongeneticists (Kruszka, Addissie, et al, ; Kruszka, Porras, et al, ; Kruszka, Porras, Sobering, et al, ; Kruszka et al, ; Kruszka et al, ). This tool is especially significant given the shortage of trained medical geneticists (Maiese, Keehn, Lyon, Flannery, & Watson, ).…”