predicted v. real prevalence of the 22q11.2 deletion syndrome in children with congenital heart disease presenting to Red Cross War Memorial Children’s Hospital, South Africa: A prospective study

Abstract

Background. The 22q11.2 deletion syndrome (22qDS) has more than 180 associated phenotypic features, yet genotype-phenotype correlation remains obscure. Since many of the clinical characteristics are serious, yet treatable (including congenital heart disease), clinicians must maintain a high index of clinical suspicion to recognise a suite of co-occurring phenotypic features that suggest a diagnosis of 22qDS. Óskarsdottir's scoring schedule (the 'O score') is generally used to suggest the need for confirmatory fluorescent in situ hybridisation (FISH) testing, using the TUPLE 1 probe. An O score of two or more indicates the need for FISH testing. Objectives. A previous audit of FISH-positive results of patients with congenital heart disease at Red Cross War Memorial Children's Hospital (RCWMCH) revealed a clinical recognition rate of 1.7%. However, we were concerned that the syndrome may be under-recognised in our setting. Our aims were therefore to assess the predictive value of 'O scoring' and to accurately determine the prevalence of 22qDS in our patient population. Methods. A prospective trial of FISH testing every new patient with congenital heart disease presenting to RCWMCH was undertaken to accurately determine the prevalence of 22qDS. The results were then compared with the ability of the O score to indicate the need for FISH testing. Results. Testing of 125 patients detected deletions in six (4.8%, 2.8 times the previously determined clinical detection rate), thereby vindicating our concern that 22qDS is under-diagnosed. Of these 125 patients, 37 had an O score of 2 or 3, yet only 6 were FISH-positive, giving the O score a positive predictive value of only 14%. Conclusion. Until a more robust alternative recognition tool is available, South African clinicians should use all clinical recognition criteria liberally to suggest the need for formal testing for 22qDS.

22q11.2 deletion syndrome in diverse populations

“…Our first finding mirrors previous studies (De Decker et al, ; McDonald‐McGinn et al, ; Veerapandiyan et al, ; Wichajam and Kampan, ) demonstrating that the clinical presentation is variable among different populations group, making the diagnosis potentially difficult. Our group of examiners for the present study and groups in the medical literature had the most difficulty diagnosing individuals of African descent with 22q11.2 DS.…”

“…The sensitivity of facial analysis technology is equal to or greater than 96.6% for each diverse population, and specificity is equal to greater than 96.3% (Table ). When using a scoring system designed from a European cohort (Oskarsdottir et al, ), De Decker et al () found the scoring system to only have a positive predictive value of 14% when applied to 125 South African individuals with congenital heart disease. Applying the prevalence of 22q11.2 DS cases in De Decker et al's South African study of 4.8%, our facial analysis technology application would give a positive predictive value of 55% using the sensitivity and specificity found in Table , a fourfold increase over the diagnostic criteria used in their study (De Decker et al, ).…”

“…When using a scoring system designed from a European cohort (Oskarsdottir et al, ), De Decker et al () found the scoring system to only have a positive predictive value of 14% when applied to 125 South African individuals with congenital heart disease. Applying the prevalence of 22q11.2 DS cases in De Decker et al's South African study of 4.8%, our facial analysis technology application would give a positive predictive value of 55% using the sensitivity and specificity found in Table , a fourfold increase over the diagnostic criteria used in their study (De Decker et al, ). As noted above, Liu et al () found that one individual with 22q11.2 DS goes undiagnosed for every 10 individuals in their cohort of Chinese adults with conotruncal heart defects.…”

“…Further studies were ascertained using reference lists of papers pertaining to 22q11.2 DS. After obtaining journal permissions, photos of 22q11.2 DS patients were used to supplement study participants described below (De Decker et al, ; Grassi et al, ; Liu et al, ; Uwineza et al, ; Veerapandiyan et al, ).…”

FAMILIAL CASE OF CHROMOSOME 22q11.2 DELETION SYNDROME

“…Согласно литературным данным, синдром де-леции 22q11.2 встречается с частотой 1 на 3000-6000 живорожденных [11,17], иногда частота синдрома в некоторых популяциях выше и может достигать 1 на 1000 [7,12,16], поражает оба пола одинаково, наследуется по аутосомно-доминант-ному типу. Около 93% пациентов имеют деле-цию, возникшую de novo, и только 7% пациентов наследуют ее от родителей [3,4,10].…”