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Immunodeficiency in patients with 49,XXXXY chromosomal variation


  • Michael D. Keller,

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    • 3550 Market Street, 3rd Floor, Philadelphia, PA 19104.
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    • Michael Keller is a clinical fellow in the division of Allergy & Immunology at the Children's Hospital of Philadelphia. His research focuses on the pathogenesis of several forms of primary immunodeficiency, with an emphasis on common variable immunodeficiency (CVID).

  • Teresa Sadeghin,

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    • Teresa Sadeghin has been working with young children since 1970. She is an administrator at the Neurodevelopmental Diagnostic Center for Young Children as well as The Focus Foundation. Mrs. Sadeghin coordinates studies and serves as a liaison to parents and organizes specialty programs.

  • Carole Samango-Sprouse,

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    • Carole Samango-Sprouse is the Director of the Neurodevelopmental Diagnostic Center for Young Children and an Associate Professor of Pediatrics at George Washington University. She is also the founder and director of The Focus Foundation, a not-for-profit organization created to help children overcome learning and chromosomal differences.

  • Jordan S. Orange

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    • Jordan Orange is a Professor and head of the division of Allergy, Immunology, and Rheumatology at Texas Children's Hospital. His laboratory researches the pathogenesis of primary immunodeficiency, and specializes in disorders of Natural Killer (NK) cells.

  • Carole Samango-Sprouse and Jordan S. Orange are Joint senior authors.

  • How to Cite this Article:Keller MD, Sadeghin T, Samango-Sprouse C, Orange JS. 2013. Immunodeficiency in patients with 49,XXXXY chromosomal variation. Am J Med Genet Part C Semin Med Genet 163C: 50–54.


Boys affected with 49,XXXXY sex chromosomal variation have been described to have high incidence of recurrent otitis media and asthma, the cause of which is unknown. We hypothesized that primary immunodeficiency occurs in patients with XXXXY aneuploidy. To investigate this, 31 boys with known 49,XXXXY were evaluated through a multidisciplinary clinic. Screening history was performed using the “10 Warning Signs of primary immunodeficiency” (Jeffrey Modell Foundation), as well as by history of atopic and autoimmune conditions. Of the 31 boys, 20 had at least two warning signs of primary immunodeficiency, and five had four or more signs. Sixteen had history of recurrent pneumonia, and 15 carried the diagnosis of asthma. Of the 10 who underwent immunologic screening, eight showed some evidence of impaired antibody responses to polysaccharide antigens, and one was diagnosed with specific antibody deficiency. These preliminary results suggest a high incidence of both atopy and antibody deficiency in boys with 49,XXXXY. © 2013 Wiley Periodicals, Inc.