Review and Feature Article
The Diverse Clinical Features of Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome)

https://doi.org/10.1016/j.jaip.2013.08.003Get rights and content

A 2-year-old boy with chromosome 22q11.2 deletion syndrome was referred for recurrent sinopulmonary infections. He was diagnosed shortly after birth by a fluorescence in situ hybridization test that was performed due to interrupted aortic arch type B. He had no hypocalcemia, and his recovery from cardiac repair was uneventful. He had difficulty feeding and gained weight slowly, but, otherwise, there were no concerns during his first year of life. At 15 months of age, he began to develop significant otitis media and bronchitis. He was hospitalized once for pneumonia at 18 months of age and has never been off antibiotics for more than 1 week since then. He has not had any previous immunologic evaluation.

Recurrent sinopulmonary infections in a child with chromosome 22q11.2 deletion syndrome can have the same etiologies as in any other child. Atopy, anatomic issues, cystic fibrosis, and new environmental exposures could be considered in this setting. Early childhood can be problematic for patients with chromosome 22q11.2 deletion syndrome due to unfavorable drainage of the middle ear and sinuses. Atopy occurs at a higher frequency in 22q11.2 deletion syndrome, and these children also have a higher rate of gastroesophageal reflux and aspiration than the general population. As would be appropriate for any child who presents with recurrent infections at 2 years of age, an immunologic evaluation should be performed. In this review, we will highlight recent findings and new data on the management of children and adults with chromosome 22q11.2 deletion syndrome.

Section snippets

Key Phenotypic Features

The cardiac defects are generally apparent shortly after birth, and the repair of these anomalies is usually the most significant aspect of clinical care in the first few weeks of life.5 Another feature that can present in the first 1 or 2 weeks of life is hypocalcemia. Chromosome 22q11.2 deletion syndrome is the most common cause of congenital hypoparathyroidism, and prompt attention to the calcium levels as well as vitamin D replacement is warranted. Although conotruncal cardiac anomalies and

The Immune Deficiency

The basis for the phenotype of chromosome 22q11.2 deletion syndrome is the abnormal development of the third pharyngeal pouch. It can result in agenesis or hypoplasia of the parathyroid glands and the thymus. In very few patients, <1% with chromosome 22q11.2 deletion syndrome, the thymus and the T cells are absent, and this is referred to as complete DiGeorge syndrome. In 75% of patients, the immune system is affected to some degree, which leaves approximately 20% of patients with normal T-cell

Transplantation

Immune system reconstitution is essential for patients with complete DiGeorge syndrome and can be accomplished by 2 means, by thymus tissue transplantation or, alternatively, by a fully matched peripheral blood T-cell transplantation.50 As expected, hematopoietic cell transplantation does not result in ongoing T-cell lymphopoiesis with the majority having persistent CD4+ T-cell lymphopenia and a skewed T-cell receptor repertoire.51, 52 Although it is not clear if the lack of lymphopoiesis

Allergic and Autoimmune Disease

Allergic disease appears to be more common in patients with chromosome 22q11.2 deletion syndrome compared with the general population and could contribute to the increased frequency of upper respiratory infections,61 which may be explained by preferential differentiation of Th2 cells in the homeostatic expansion of T cells as has been observed in mice.62 Autoimmune disease is seen in approximately 10% of patients with deletion syndrome.17 Most commonly reported are hematologic autoimmune

The Opening Vignette

The immunologic evaluation of the 2-year-old boy described in the abstract demonstrated a low-for-age T-cell count (CD3), at 848 cells/mm3, with a CD4+ T-cell count of 573 cells/mm3. His naive-to-memory T-cell ratio was advanced, which had a higher proportion of memory T cells than expected for his age, but his quantitative immunoglobulin levels were normal as well as were antibody titers to pneumococcal, diphtheria, and tetanus vaccines. He was cleared to receive live viral vaccines and was

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    Supported by the Wallace Chair of Pediatrics.

    Conflicts of interest: The authors declare that they have no relevant conflicts of interest.

    Cite this article as: Maggadottir SM, Sullivan KE. The diverse clinical features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome). J Allergy Clin Immunol Pract 2013;1:589-94. http://dx.doi.org/10.1016/j.jaip.2013.08.003.

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