New Syndrome

Fatal lung fibrosis associated with immunodeficiency and gonadal dysgenesis in 46XX sisters—A new syndrome†

  1. Raz Somech1,
  2. Gino R. Somers2,
  3. David Chitayat3,
  4. Eyal Grunebaum1,
  5. Adelle Atkinson1,
  6. Elena Kolomietz4,
  7. Chaim M Roifman1,*

Article first published online: 15 OCT 2007

DOI: 10.1002/ajmg.a.32014

Issue

American Journal of Medical Genetics Part A

American Journal of Medical Genetics Part A

Volume 146A, Issue 1, pages 8–14, 1 January 2008

Additional Information

How to Cite

Somech, R., Somers, G. R., Chitayat, D., Grunebaum, E., Atkinson, A., Kolomietz, E. and Roifman, C. M. (2008), Fatal lung fibrosis associated with immunodeficiency and gonadal dysgenesis in 46XX sisters—A new syndrome. Am. J. Med. Genet., 146A: 8–14. doi: 10.1002/ajmg.a.32014

Author Information

  1. 1

    Department of Pediatrics, Division of Immunology and Allergy, The Canadian Centre for Primary Immunodeficiency, The Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

  2. 2

    Department of Pediatrics, Division of Laboratory Medicine and Pathobiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

  3. 3

    Department of Pediatrics, Division of Medical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

  4. 4

    Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

*Division of Immunology and Allergy, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada.

  1. †

    How to cite this article: Somech R, Somers GR, Chitayat D, Grunebaum E, Atkinson A, Kolomietz E, Roifman CM. 2007. Fatal lung fibrosis associated with immunodeficiency and gonadal dysgenesis in 46XX sisters—A new syndrome. Am J Med Genet Part A 146A:8–14.

Publication History

  1. Issue published online: 19 DEC 2007
  2. Article first published online: 15 OCT 2007
  3. Manuscript Accepted: 16 JUL 2007
  4. Manuscript Received: 6 SEP 2006

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Keywords:

  • XX;
  • gonadal dysgenesis;
  • lung fibrosis;
  • lethal;
  • immunodeficiency

Abstract

Inherited immune deficiencies are a heterogeneous group of diseases that can be either isolated, with the immune defect being the exclusive manifestation, or associated with other abnormalities. We report on two sisters, born to consanguineous parents of Sri-Lankan descent, who presented in infancy with immunodeficiency, gonadal dysgenesis, and fatal lung fibrosis. Immune studies demonstrated combined humoral and cellular abnormalities including reduced immunoglobulin production, an absence of lymphoid tissue, markedly reduced T-lymphocyte numbers and function and reduced newly thymus-derived T-cells. Both infants succumbed to rapidly progressive lung fibrosis. Autopsy showed dysgenetic gonads bearing no discernible oocytes. In both, karyotypes were normal female (46,XX). Comparative genome hybridization and analysis of genes known to be associated with severe immune defects in infancy or gonadal dysgenesis showed no abnormality. The distinct findings in these two sisters have not been reported before and thus suggest a hitherto unknown autosomal recessive condition that includes immune dysfunction, gonadal dysgenesis, and pulmonary fibrosis. © 2007 Wiley-Liss, Inc.

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