Which genetic tests are recommended for confirming a diagnosis of DiGeorge Syndrome?

Recommended genetic tests for confirming a diagnosis of DiGeorge syndrome (22q11.2 deletion syndrome) primarily include fluorescence in situ hybridisation (FISH) and chromosomal microarray analysis (CMA), with CMA being the preferred first-line diagnostic test due to its higher resolution and ability to detect smaller deletions.

FISH has historically been used to detect the typical 3 Mb deletion at chromosome 22q11.2, which is the most common cause of DiGeorge syndrome, but it may miss atypical or smaller deletions. CMA, on the other hand, can identify both typical and atypical deletions across the 22q11.2 region, providing a more comprehensive genetic diagnosis ¹.

Additionally, multiplex ligation-dependent probe amplification (MLPA) can be used as a complementary test to confirm deletions detected by CMA or FISH, especially in cases where clinical suspicion remains high despite negative initial testing (Kuo et al., 2018; Urschel and Hernandez-Trujillo, 2022).

Recent literature also highlights the role of next-generation sequencing (NGS) panels targeting genes within the 22q11.2 region and related immunodeficiency genes to further characterise the genetic spectrum and associated phenotypes, although this is not yet standard for initial diagnosis (Blagowidow et al., 2023).