Published online April 27, 2009
PEDIATRICS Vol. 123 No. 5 May 2009, pp. e871-e877 (doi:10.1542/peds.2008-3400)
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ARTICLE

CHARGE (Coloboma, Heart Defect, Atresia Choanae, Retarded Growth and Development, Genital Hypoplasia, Ear Anomalies/Deafness) Syndrome and Chromosome 22q11.2 Deletion Syndrome: A Comparison of Immunologic and Nonimmunologic Phenotypic Features

Soma Jyonouchi, MDa, Donna M. McDonald-McGinn, MS, CGCb, Sherri Bale, PhDc, Elaine H. Zackai, MDb and Kathleen E. Sullivan, MD, PhDa

a Divisions of Allergy and Immunology
b Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
c Gene Dx, Gaithersburg, Maryland

OBJECTIVES. CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome are known to have significant clinical overlap including cardiac anomalies, ear abnormalities, hearing loss, developmental delay, renal abnormalities, and cleft palate. Immunodeficiency has been well documented in 22q11.2 deletion, but there has been limited recognition of this potentially serious complication in CHARGE syndrome. The goals of our study were to identify clinical features unique to CHARGE syndrome or 22q11.2 deletion and to describe the spectrum of immunodeficiency found in patients with CHARGE syndrome.

METHODS. This study included 25 children diagnosed with CHARGE syndrome with positive CHD7 mutations through the Children's Hospital of Philadelphia genetics program. Clinical features and laboratory findings were reviewed retrospectively. We compared our findings to data available for a large cohort of patients with 22q11.2 deletion syndrome followed in our clinical genetics program.

RESULTS. Features found more commonly in CHARGE syndrome included coloboma, choanal atresia, facial nerve palsy, tracheoesophageal fistula, and genital hypoplasia in boys. A high incidence of marked hypocalcemia was observed in our study group (72%). We found a spectrum of cell-mediated immunodeficiency in our study group, which ranged from lymphopenia (60%) to severe combined immunodeficiency (8%). Defects in humoral immunity were documented in 4 patients and included severe hypogammaglobulinemia with decreased T-cell numbers, transient hypogammaglobulinemia during infancy, and immunoglobulin A deficiency.

CONCLUSIONS. The presence of coloboma, choanal atresia, facial nerve palsy, tracheoesophageal fistula, or genital hypoplasia in boys should alert the clinician to the possibility of CHARGE syndrome rather than the 22q11.2 deletion. Molecular testing for CHD7 mutations may help to confirm the diagnosis. In this study, significant hypocalcemia and lymphopenia occurred more frequently in patients with CHARGE syndrome than in those with 22q11.2 deletion syndrome. Early inclusion of immunologists to the multidisciplinary care team (as with 22q11.2 deletion) may be of great benefit to affected patients.

Key Words: CHARGE syndrome • CHD7 • DiGeorge syndrome • chromosome 22q11.2 deletion • velocardiofacial syndrome • TBX-1 • thymus • SCID • T cell • immunodeficiency • hypocalcemia

Abbreviations: CHARGE—coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness • DGS—DiGeorge syndrome • CHD7—chromodomain helicase DNA-binding protein 7 • SCID—severe combined immunodeficiency • NK—natural killer • Ig—immunoglobulin

Accepted Jan 21, 2009.


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