Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome

Abstract

Summary Chromosome 22q11.2 deletion syndrome is the most common microdeletion syndrome in humans. The effects are protean and highly variable, making a unified approach difficult. Nevertheless, commonalities have been identified and white papers with recommended evaluations and anticipatory guidance have been published. This review will cover the immune system in detail and discuss both the primary features and the secondary features related to thymic hypoplasia. A brief discussion of the other organ system involvement will be provided for context. The immune system, percolating throughout the body can impact the function of other organs through allergy or autoimmune disease affecting organs in deleterious manners. Our work has shown that the primary effect of thymic hypoplasia is to restrict T cell production. Subsequent homeostatic proliferation and perhaps other factors drive a Th2 polarization, most obvious in adulthood. This contributes to atopic risk in this population. Thymic hypoplasia also contributes to low regulatory T cells and this may be part of the overall increased risk of autoimmunity. Collectively, the effects are complex and often age‐dependent. Future goals of improving thymic function or augmenting thymic volume may offer a direct intervention to ameliorate infections, atopy, and autoimmunity.

HIRA, a DiGeorge Syndrome Candidate Gene, Confers Proper Chromatin Accessibility on HSCs and Supports All Stages of Hematopoiesis

“…The HIRA gene maps to Chr22q11.21 in humans. In patients with DiGeorge syndromes, also referred to as Chr22q11 deletion syndromes, the genomic region encompassing HIRA, a 5-3 Mb DNA stretch, is deleted (Akar and Adekile, 2007;D'Antoni et al, 2004;Lindsay, 2001;Sullivan, 2019). The deleted regions contain not only HIRA but additional genes, including TBX1, involved in embryonic development.…”

Orthopedic and orthodontic management in a patient with DiGeorge Syndrome and Familial Mediterranean Fever: A case report

“…The clinical management is age dependent, focusing on acute medical problems and developmental disorders in infancy and the preschool years . The guidelines for the management of patients with DiGeorge syndrome have been developed and summarized by Bassett et al in their paper .…”

“…18 The clinical management is age dependent, focusing on acute medical problems and developmental disorders in infancy and the preschool years. 19 The guidelines for the management of patients with DiGeorge syndrome have been developed and summarized by Bassett et al in their paper. 20 People living with 22q11.2del need medical specialists support during all their life, including geneticists, immunologists, cardiologists, and speech specialists.…”

Introduction: Continuing insights into the healthy and diseased immune system through human genetic investigation

“…Most reviews focus on specific disease entities linked to single gene defects, that are now listed in the Online Mendelian Inheritance in Man (OMIM), such as DOCK8 deficiency (OMIM 611432), Complement hyperactivation, angiopathic thrombosis and protein‐losing enteropathy hyperactivation (CHAPLE, OMIM 226300), CTLA‐4 haploinsufficiency with autoimmunity and inflammation (CHAI, OMIM 616100), autoimmune lymphoproliferative syndrome (ALPS, OMIM six601859) and Ras‐associated lymphoproliferative disease (RALD, OMIM 614470) due to Fas and Ras mutations, respectively, ADA2 deficiency (OMIM 615688), Omenn syndrome (OMIM 603554) and other deficits of the recombinase activating genes RAG1 and RAG2 (OMIM 179615), warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis (WHIM, OMIM 193670) syndrome due to CXCR4 mutations, autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) due to AIRE gene mutations (OMIM 240300), Wisott‐Aldrich syndrome and actin regulatory protein deficiencies due to WAS and WIP mutations, among others . In addition, there are reviews on classes of disorders, such as allergy and atopy, common variable immunodeficiency, early‐onset inflammatory bowel disease, and Chromosome 22.q11.2 and DiGeorge syndrome . Finally, some monographs address specific components of the immune system, such as NK cells, tissue neutrophils, and regulatory T cells .…”

“…13 In addition, there are reviews on classes of disorders, such as allergy and atopy, 14 common variable immunodeficiency, 15 early-onset inflammatory bowel disease, 16 and Chromosome 22.q11.2 and DiGeorge syndrome. 17 Finally, some monographs address specific components of the immune system, such as NK cells, 18 tissue neutrophils, 19 and regulatory T cells. 20 Finally, we have a critical assessment of how clinical molecular advances are brought into the realm of public health by perinatal testing for T cell receptor excision circles or TRECs.…”