Expanding the Prenatal Phenotype and Genotype of 22q11.2 Deletion Syndrome through Genome-wide Chromosomal Microarray Analysis
Seema Thakur, Preeti Paliwal, Chanchal Singh, Shreyasi Sharma, Vrunda Appannagari, Shreya Goel, N Mohit, Gurnihal Singh Chawla, Savita Dagar, Tanu Gera, Shivam Batra, Rounak Bagga, Vibha Mital, Himani KaushikAbstract
Background:
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is one of the most common recurrent microdeletion syndromes, traditionally identified prenatally through conotruncal cardiac anomalies on ultrasound. With the increasing use of chromosomal microarray analysis (CMA), the recognized prenatal phenotype now includes a broader range of structural and subtle findings as well as atypical deletions.
Methodology:
We retrospectively reviewed nine prenatally diagnosed cases of 22q11.2 deletions from three fetal medicine centers, characterizing clinical presentations, CMA findings, inheritance patterns, and counseling challenges.
Results:
Five cases presented with classical cardiac anomalies, while four exhibited atypical or incidental findings such as hypoplastic nasal bone, borderline enlarged cisterna magna, increased nuchal fold, and isolated soft markers. CMA identified both classic deletions and smaller, nested, or distal variants including inherited deletions from phenotypically unaffected parents. The variability in phenotype, genotype, and inheritance patterns complicated prenatal counseling in predicting postnatal outcomes.
Conclusion:
Genome-wide CMA substantially expands both the phenotypic and genotypic spectrum of 22q11.2DS detectable prenatally, revealing cases beyond the resolution of traditional testing and ultrasound alone. Multidisciplinary counseling and long-term follow-up are essential to address incomplete penetrance and variable expressivity. In 22q11.2DS, CMA uncovers a far wider prenatal spectrum than ultrasound, underscoring the need for integrated counseling frameworks and outcome tracking to translate the diagnosis into truly informed care.