Background: 22q11.2 microdeletion in patients with conotruncal malformations significantly impacts patient management and counseling. Marked phenotypic variability makes clinical prediction difficult. Diagnostic cytogenetic testing has limited availability in most developing nations and may take several days.
Objectives: To identify frequency of 22q11 microdeletion and the most specific phenotypic markers for its clinical prediction in a large cohort of Indian children ≤ 2 years with conotruncal malformations.
Methods: Prospective, hospital-based, observational study conducted at a tertiary care hospital in India. Conotruncal anomalies were identified through echocardiography. Independent phenotypic evaluation was done by pediatric geneticist (blinded to cardiac diagnosis). Cytogenetic diagnosis was established through fluorescent in-situ hybridization (FISH). Genotype-phenotype correlations were studied using multivariate logistic regression analysis.
Results: FISH was positive for microdeletion 22q11.2 in 32 of 150 patients (21.3%). Frequency in individual lesions was- truncus arteriosus (55.6%), interrupted aortic arch (50%), TOF/PA (30%), conoventricular VSD (21.1%), DORV (18.8%), simple TOF (12.9%) and TOF/absent pulmonary valve (0%). Among the 24 phenotypic variables studied, bulbous nasal tip (OR-16.7, p < 0.001), dysplastic flared pinnae (OR - 9, p 0.003), microstomia (OR-10.7, p 0.002), thin long fingers (OR-3.4, p 0.066), and hypocalcemia (OR- 25, p 0.001) emerged as predictors of 22q11 microdeletion on multivariate analysis. Discriminant analysis provided a computational scoring model to clinically predict 22q11.2 deletion with correct classification in 75.3% cases.
Conclusions: This study identifies specific phenotypic guidelines for bed-side prediction of 22q11 microdeletion and may assist in better management and counseling for conotruncal malformations when cytogenetic diagnosis is awaited or unavailable.