Immune Dysfunction in Children with CHARGE Syndrome: A Cross-Sectional Study

Area of Science:

• Immunology
• Genetics
• Pediatrics

Background:

• CHARGE syndrome is a complex congenital malformation syndrome.
• Frequent infections in CHARGE syndrome are often attributed to anatomical issues, but immune dysfunction is understudied.
• Clinical overlap exists between CHARGE syndrome and 22q11.2 deletion syndrome, where immune deficiencies are known.

Purpose of the Study:

• To investigate the frequency and nature of immune dysfunction in children with genetically confirmed CHARGE syndrome.
• To assess the contribution of immunological abnormalities to recurrent infections in CHARGE syndrome patients.

Main Methods:

• Studied 24 children with genetically proven CHARGE syndrome.
• Collected infectious history via questionnaires.
• Performed comprehensive immunological assessments including blood counts, immunoglobulin levels, lymphocyte subpopulations, T-cell analysis (TREC), T-cell function, and vaccination responses.

Main Results:

• All CHARGE syndrome patients reported a history of frequent infections (otitis media, pneumonia), necessitating antibiotics and hospitalizations.
• 50% of patients had decreased T-cell numbers, linked to diminished T-receptor excision circle (TREC) amounts, suggesting insufficient thymic output.
• 83% of patients exhibited insufficient antibody titers to standard childhood vaccinations, despite normal B-cell differentiation and immunoglobulin production.

Conclusions:

• CHARGE syndrome is associated with significant immune system abnormalities, including T-cell deficiencies and impaired vaccine responses.
• Immunological evaluation is recommended for CHARGE syndrome patients experiencing recurrent infections.
• These findings highlight the importance of considering immune dysfunction in the management of CHARGE syndrome.