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Microcephaly, Recurrent Infections and Failure to Thrive

  • Mihaela Tatiana Bataneant
Chapter

Abstract

  • The clinical phenotype of DNA ligase IV deficiency, overlaps with other rare diseases, including Seckel syndrome, Nijmegen breakage and Cernunnos syndrome and the diagnosis is established by exclusion

  • DNA ligase IV deficiency is characterized by severe T and B lymphopenia with microcephaly

  • Hematopoietic stem-cell transplantation is the single curative treatment in DNA ligase IV, there is still a lot of knowledge missing

Keywords

DNA ligase IV deficiency Severe combined immunodeficiency Hematopoietic stem-cell transplantation Cernunnos 

References

  1. 1.
    Arkwright PD, Gennery AR. Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci. 2011;1238:7–14.CrossRefGoogle Scholar
  2. 2.
    Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, Roberts JL, Puck JM. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997;130(3):378–87.CrossRefGoogle Scholar
  3. 3.
    Subbarayan A, Colarusso G, Hughes SM, Gennery AR, Slatter M, Cant AJ, Arkwright PD. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011;127(5):810–6.CrossRefGoogle Scholar
  4. 4.
    de Vries E. Patient-centred screening for primary immunodeficiency, a multi-stage diagnostic protocol designed for non-immunologists: 2011 update. Clin Exp Immunol. 2012;167(1):108–19.CrossRefGoogle Scholar
  5. 5.
    Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol. 2004;22:625–55.CrossRefGoogle Scholar
  6. 6.
    Rass U, Ahel I, West SC. Defective DNA repair and neurodegenerative disease. Cell. 2007;130(6):991–1004.CrossRefGoogle Scholar
  7. 7.
    O’Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell. 2001;8(6):1175–85.CrossRefGoogle Scholar
  8. 8.
    Ben-Omran TI, Cerosaletti K, Concannon P, Weitzman S, Nezarati MM. A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome. Am J Med Genet A. 2005;137a(3):283–7.CrossRefGoogle Scholar
  9. 9.
    Buck D, Moshous D, de Chasseval R, Ma Y, le Deist F, Cavazzana-Calvo M, Fischer A, Casanova JL, Lieber MR, de Villartay JP. Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV. Eur J Immunol. 2006;36(1):224–35.CrossRefGoogle Scholar
  10. 10.
    Enders A, Fisch P, Schwarz K, Duffner U, Pannicke U, Nikolopoulos E, Peters A, Orlowska-Volk M, Schindler D, Friedrich W, Selle B, Niemeyer C, Ehl S. A severe form of human combined immunodeficiency due to mutations in DNA ligase IV. J Immunol. 2006;176(8):5060–8.CrossRefGoogle Scholar
  11. 11.
    Nijmegen breakage syndrome. The International Nijmegen Breakage Syndrome Study Group. Arch Dis Child. 2000;82(5):400–6.Google Scholar
  12. 12.
    O’Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet. 2003;33(4):497–501.CrossRefGoogle Scholar
  13. 13.
    Bobabilla-Morales L, Corona-Rivera A, Corona-Rivera JR, Buenrostro C, Garcia-Cobian TA, Corona-Rivera E, Cantu-Garza JM, Garcia-Cruz D. Chromosome instability induced in vitro with mitomycin C in five Seckel syndrome patients. Am J Med Genet A. 2003;123a(2):148–52.CrossRefGoogle Scholar
  14. 14.
    Buck D, Malivert L, de Chasseval R, Barraud A, Fondaneche MC, Sanal O, Plebani A, Stephan JL, Hufnagel M, le Deist F, Fischer A, Durandy A, de Villartay JP, Revy P. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell. 2006;124(2):287–99.CrossRefGoogle Scholar
  15. 15.
    Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O’Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol. 2014;133(4):1092–8.CrossRefGoogle Scholar
  16. 16.
    Gruhn B, Seidel J, Zintl F, Varon R, Tonnies H, Neitzel H, Bechtold A, Hoehn H, Schindler D. Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure. Orphanet J Rare Dis. 2007;2:5.CrossRefGoogle Scholar
  17. 17.
    Altmann T, Gennery AR. DNA ligase IV syndrome; a review. Orphanet J Rare Dis. 2016;11:137.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mihaela Tatiana Bataneant
    • 1
    • 2
  1. 1.“Victor Babes” University of Medicine and PharmacyTimisoaraRomania
  2. 2.“Louis Turcanu” Children’s Emergency Clinical HospitalTimisoaraRomania

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