Faculty Collaboration Database

Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: a cross-sectional analysis from population-based newborn screening. CMAJ Open 2021;9(3):E802-E809

Date

08/19/2021

Pubmed ID

34404688

Pubmed Central ID

PMC8373039

DOI

10.9778/cmajo.20200294

Scopus ID

2-s2.0-85114430327 (requires institutional sign-in at Scopus site)   66 Citations

Abstract

BACKGROUND: Although pathogenic 22q11.2 deletions are an important cause of developmental delays and lifelong disease burden, their variable and complex clinical expression contributes to under-recognition, delayed molecular diagnosis and uncertainty about prevalence. We sought to estimate the contemporary live-birth prevalence of typical 22q11.2 deletions using a population-based newborn screening sample and to examine data available for associated clinical features.

METHODS: Using DNA available from an unbiased sample of about 12% of all dried blood spots collected for newborn screening in Ontario between January 2017 and September 2018, we prospectively screened for 22q11.2 deletions using multiplex quantitative polymerase chain reaction assays and conducted independent confirmatory studies. We used cross-sectional analyses to compare available clinical and T-cell receptor excision circle (TREC, used in newborn screening for severe combined immunodeficiency) data between samples with and without 22q11.2 deletions.

RESULTS: The estimated minimum prevalence of 22q11.2 deletions was 1 in 2148 (4.7 per 10 000) live births (95% confidence interval [CI] 2.5 to 7.8 per 10 000), based on a total of 30 074 samples screened, with 14 having confirmed 22q11.2 deletions. Of term singletons, samples with 22q11.2 deletions had significantly younger median maternal age (25.5 v. 32.0 yr, difference -6.5 yr, 95% CI -7 to -2 yr), a greater proportion with small birth weight for gestational age (odds ratio 7.00, 95% CI 2.36 to 23.18) and lower median TREC levels (108.9 v. 602.5 copies/3 μL, p < 0.001).

INTERPRETATION: These results indicate that the 22q11.2 deletion syndrome is one of the most common of rare genetic conditions and may be associated with relatively younger maternal ages and with prenatal growth abnormalities. The findings support the public health importance of early - prenatal and neonatal - diagnosis that would enable prompt screening for and management of well-known actionable features associated with 22q11.2 deletions.

Author List

Blagojevic C, Heung T, Theriault M, Tomita-Mitchell A, Chakraborty P, Kernohan K, Bulman DE, Bassett AS

Author

Aoy Tomita Mitchell PhD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cross-Sectional Studies
Developmental Disabilities
DiGeorge Syndrome
Early Medical Intervention
Female
Gestational Age
Humans
Infant, Low Birth Weight
Infant, Newborn
Live Birth
Male
Maternal Age
Molecular Diagnostic Techniques
Neonatal Screening
Ontario
Prenatal Diagnosis
Prevalence
Severe Combined Immunodeficiency