• 22q11.2 deletion
• tetralogy of Fallot
• 22q11 deletion syndrome

Interstitial deletions of chromosome 22q11.2 are associated with several birth defects and malformations, which include DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes. These were all initially described as separate entities, but are now considered to be part of the spectrum of the same condition. The CATCH22 acronym was proposed to encompass this phenotypic variability,¹ but the term “22q11 deletion syndrome” is considered to be more appropriate.²

22q11.2 deletions are estimated to occur at a frequency of 1 in 4000 live births, and it is considered to be the most common known deletion disorder in humans.³ Around 90-95% of 22q11 deletion syndrome cases are sporadic, suggesting that this region is prone to deletions.^3,4 The finding that most deletions were similar suggested that there might be sequences at the breakpoints that confer susceptibility to chromosome rearrangements. Edelmann et al⁵ reported the presence of highly homologous low copy repeats in the 22q11 region (LCR22s), which mapped to the proximal and distal interval breakpoints of the common 3 Mb deletions in patients with velocardiofacial syndrome. This finding suggested that misalignment in intrachromosomal homologous recombination events could lead to the 3 Mb deletion.

Around 90% of 22q11 deletion syndrome patients are found to have a 3 Mb deletion, known as the common or “typical deleted region”, which may contain about 30 functional genes. About 7% have a smaller 1.5 Mb deletion. Atypical or unique deletions or translocations have also been found in a few rare patients.⁶ Deletion studies have narrowed down the “minimal DiGeorge critical region” to the proximal 250 kb of the typical deleted region.⁷ However, to date seven patients have been reported with atypical deletions that show no overlap with this critical region.^8–14 These cases are extremely valuable as they may provide some …