Case reports
Selective IgM deficiency and 22q11.2 deletion syndrome

https://doi.org/10.1016/S1081-1206(10)60627-8Get rights and content

Background

The 22q11.2 deletion syndrome is a common chromosomal disorder with highly variable phenotypic expression and immunologic defects. Humoral immunity is mostly unaffected, but selective IgA deficiency occurs in up to 13% of patients. Selective IgM deficiency associated with 22q11.2 deletion has been reported in 1 patient.

Objective

To describe another 2 patients with 22q11.2 deletion syndrome and IgM deficiency.

Methods

Patient 1 was a 6-year-old boy with recurrent otitis media, sinopulmonary infections, wheezing, and speech delay. His serum IgM level was 18 mg/dL, and his IgA and IgG levels were normal. Antibody titers to protein and carbohydrate antigens were protective. Workup for velopharyngeal insufficiency resulted in the diagnosis of 22q11.2 deletion syndrome 3 years later. Patient 2 was a 14-year-old girl diagnosed as having 22q11.2 deletion at 9 years of age after presenting with neonatal seizures, atrial and ventricular septal defects, recurrent otitis media, mental retardation, and asthma. Her serum IgM level was 11 mg/dL, with normal IgG and IgA levels. Antibody titers to protein and carbohydrate antigens were protective. Patient 3 was a previously described 15-year-old girl with persistently draining ears, 22q11.2 deletion, and an IgM level less than 6 mg/dL. Her clinical and laboratory features are summarized.

Results

Results of further testing on the patients, including lymphocyte enumeration, were normal. The literature is reviewed regarding decreased IgM levels in 22q11.2 deletion syndrome.

Conclusions

Fluorescence in situ hybridization analysis for chromosome 22q11.2 deletion should be considered in patients with selective IgM deficiency, especially if concurrent chronic otitis media, developmental delay, velopharyngeal insufficiency, or dysmorphic features are present.

Section snippets

INTRODUCTION

The 22q11.2 deletion syndrome is one of the most common chromosomal disorders, with an estimated prevalence of 1:4,000 to 1:6,000.1, 2, 3 Phenotypic expression is highly variable, with clinical presentations ranging from DiGeorge and velocardiofacial syndromes to velopharyngeal insufficiency (VPI) and schizophrenia.4, 5 Similarly, the effect on the immune system varies widely. Whereas earlier studies described severe cellular immunodeficiency in patients with DiGeorge syndrome, more recent

Case 1

A 6-year-old white boy was referred for evaluation of chronic rhinitis and recurrent infections. He was born at term to unrelated parents. Recurrent otitis media (OM) with tympanic membrane perforations began in early infancy, for which myringotomy tubes (MTs) were inserted on 2 occasions. An adenoidectomy was performed with the latter. At 3 years of age, speech therapy was initiated for speech delay. Other infections included 2 episodes of pneumonia and sinusitis and several impetiginous skin

DISCUSSION

We describe 2 additional patients with SIgMD associated with 22q11.2 deletion and review the common features of these patients and the previously described patient with the same association. Their clinical presentation is consistent with the known variable phenotype of 22q11.2 deletion syndrome. The diagnosis of 22q11.2 deletion was delayed until late childhood in all 3 patients. Other than a decreased IgM level and a suboptimal pneumococcal response in patient 3, findings from their immune

CONCLUSION

In summary, we suggest that SIgMD may be associated with 22q11.2 deletion syndrome. Review of the literature shows that decreased IgM levels and IgM deficiency occur with 22q11.2 deletion but are not as common as selective IgA deficiency.7 Cytogenetic FISH analysis for chromosome 22q11.2 deletion syndrome should be considered in a patient diagnosed as having SIgMD if there are other findings, such as chronic or recurrent OM, developmental delay, VPI, or phenotypic features of 22q11.2 deletion

REFERENCES (19)

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    In our own 22qDS cohort, 43% of the tested patients had SAD, although we cannot exclude a testing bias because these data were collected retrospectively and the patients with 22qDS tested were slightly younger. Patients with 22qDS also had lower IgM levels compared with patients with CHARGE syndrome, which is consistent with previous case reports of low IgM in this group of patients.22,23 Lymphopenia is also a common finding in children with 22qDS, with the majority of children found to have reduced lymphocyte counts.7

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The opinions and assertions contained herein are the views of the authors and are not to be construed as official or as reflecting the views of the United States Department of Defense.

Authors have nothing to disclose.

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