Why are children with DiGeorge syndrome at increased risk of developing otitis media (ear infections)?

Why Children with DiGeorge Syndrome Get Ear Infections

Children with DiGeorge syndrome develop recurrent ear infections primarily due to anatomical abnormalities—specifically palatal defects and Eustachian tube dysfunction—rather than their underlying immunodeficiency. 1

Primary Mechanism: Anatomical Defects

The dominant risk factor for recurrent otitis media with effusion in DiGeorge syndrome is the presence of palatal anomalies, which directly impair Eustachian tube function. 1 This is critical to understand because:

• Palatal defects (including cleft palate and velopharyngeal insufficiency) mechanically disrupt the normal opening and closing of the Eustachian tube, preventing proper middle ear ventilation and drainage. 2

• The Eustachian tube epithelium serves as the frontline defense against bacterial colonization from the nasopharynx through mucociliary flow and antimicrobial protein secretion. 2 When palatal anatomy is abnormal, this protective mechanism fails.

• In a large cohort study of 467 partial DiGeorge patients, palatal anomalies were identified as an independent risk factor for recurrent otitis media with effusion using multivariate analysis. 1 This demonstrates that the structural problem supersedes the immune defect in causing ear infections.

Secondary Contributing Factors

Gastroesophageal Issues

Gastroesophageal reflux and dysphagia represent additional risk factors for recurrent upper respiratory tract infections in DiGeorge patients, which subsequently predispose to otitis media. 1 Laryngopharyngeal reflux contributes to chronic inflammation of the Eustachian tube and middle ear. 3

Immunodeficiency Plays a Lesser Role

While DiGeorge syndrome involves T-cell immunodeficiency due to thymic hypoplasia or aplasia, infections in these patients represent, in most cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency. 1

However, some immune factors do contribute:

• Selective polysaccharide antibody deficiency has been documented in DiGeorge patients, with impaired IgG antibody responses to Haemophilus influenzae and Streptococcus pneumoniae—the primary bacterial otopathogens. 4

• Low serum IgM levels and IgG4 deficiency may compound the problem. 4

• CD4+ T cell lymphopenia can impair B cell help for antibody production against encapsulated bacteria. 4, 5

Clinical Algorithm for Management

Immediate Assessment

When evaluating a DiGeorge patient with recurrent ear infections, prioritize:

1. Otoscopic examination with pneumatic otoscopy to document middle ear effusion and tympanic membrane mobility. 2, 6

2. Evaluate for palatal defects: Examine for overt cleft palate, submucous cleft, or velopharyngeal insufficiency (even subtle defects matter). 1

3. Screen for gastroesophageal reflux and dysphagia, as these independently increase infection risk. 1

Treatment Approach

• Address anatomical problems first: Surgical correction of palatal defects and consideration of tympanostomy tubes for persistent effusions. 1

• Manage reflux aggressively if present, as this reduces upper respiratory tract infection frequency. 1

• Consider immunoglobulin replacement therapy if there is documented antibody deficiency with recurrent severe infections. 4

• Avoid the pitfall of attributing all infections solely to immunodeficiency—this leads to missing correctable anatomical problems. 1

Important Caveats

The immunodeficiency in partial DiGeorge syndrome is often overestimated as a cause of infections. 1 Most patients have sufficient T-cell function to handle routine pathogens, and their infection susceptibility stems from mechanical barriers to drainage and clearance. 1

Allergy and atopy are common in DiGeorge patients and may contribute to Eustachian tube inflammation and dysfunction. 5 Screen for allergic rhinitis, as this requires separate management beyond treating the structural defects. 3

Autoimmunity becomes more prominent with age in DiGeorge patients due to premature T-cell aging and lymphopenia-induced peripheral T-cell proliferation, but this is less relevant to childhood ear infections. 1, 5