Identification of 22q11.2 Deletion Syndrome via Newborn Screening for Severe Combined Immunodeficiency

Abstract

Our findings support rapidly screening infants with a positive NBS for SCID, but without SCID, for 22q11.2DS even when typically associated features such as CHD are absent, particularly when B cells and NK cells are normal. Moreover, direct NBS for 22q11.2DS using multiplex qPCR would be equally, if not more, beneficial, as early identification of 22q11.2DS will obviate a protracted diagnostic odyssey while providing an opportunity for timely assessment and interventions as needed, even in the absence of T cell lymphopenia.

Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome

“…These infants will require a matched sibling T cell transfer or a thymus transplant . The use of newborn screening for severe combined immunodeficiency has led to improved recognition of these infants and we demonstrated that unbiased testing led to early identification of infants who would not otherwise have been identified …”

“…Overall, syndromes as a general category are the most frequent final diagnosis to explain low T cell counts . We examined whether infants with 22q11.2del could be reliably identified through newborn screening for severe combined immunodeficiency . Although the sensitivity of the current newborn screening for severe combined immunodeficiency for 22q11.2del is low, approximately half of the patients identified in this way would not likely have been picked up in the newborn period otherwise.…”

“…139 We examined whether infants with 22q11.2del could be reliably identified through newborn screening for severe combined immunodeficiency. 140 A new approach developed to determine fetal risk utilizes cellfree DNA from maternal serum, an approach that limits the risk to the fetus. This effort has been developed to screen for aneuploidy and uses directed capture of DNA for analysis.…”

“…[150][151][152][153] The use of newborn screening for severe combined immunodeficiency has led to improved recognition of these infants and we demonstrated that unbiased testing led to early identification of infants who would not otherwise have been identified. 140 The second critical decision point is whether to provide live viral vaccines to an individual patient. It is clear that children with severe combined immunodeficiency and absent T cells should not be given live viral vaccines because of their inability to control even the attenuated virus in the vaccines.…”

A Cost-Effectiveness Analysis of Newborn Screening for Severe Combined Immunodeficiency in the UK

“…Of the 47 cases of DiGeorge Syndrome, 9% received a thymus transplant while the other 90% had partial DiGeorge syndrome with improving T cell function over time [21]. In a separate study of patients diagnosed with 22q11.2 Deletion Syndrome, the most common cause of DiGeorge, 45% of patients were diagnosed prior to the screening result [53]. These results show that there may be some benefit to patients who would not have been diagnosed either symptomatically or through a family history prior to the TREC screening result.…”