EBV-Related Hodgkin Lymphoma in an ICF2 Patient: Is EBV Susceptibility a Hallmark of This ICF Subtype?

  • Francesco LicciardiEmail author
  • Marlinde van den Boogaard
  • Marta Delle Piane
  • Pier Angelo Tovo
  • Davide Montin
Letter to Editor

To the Editor,

Immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF) is a rare autosomal recessive disorder caused by defective DNA methylation. So far, approximately 70 cases have been reported: 56% have mutations in DNMT3B (ICF1), 31% in ZBTB24 (ICF2), and the remaining 13% in CDCA7 (ICF3) or HELLS (ICF4) [1].

Regardless of ICF subtype, the main clinical manifestations are recurrent and severe infections due to the underlying immunodeficiency, in particular T cell lymphocytopenia and/or hypo/agammaglobulinemia and facial abnormalities, such as epicanthus, low-set ears, hypertelorism, flat nasal bridge, telecanthus, and a round face.

We describe the history of an ICF2 patient who had a chronic EBV infection and developed aggressive Hodgkin lymphoma (HL). The clinical history and the revision of literature reveal that ICF2 patients have a predisposition to EBV infection with severe complications.

Case Report

The patient was born from Italian,...



We wish to thank Dr. Paola Campisi for providing the biopsy microscopical pictures.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, “Regina Margherita” Children HospitalUniversity of TurinTurinItaly
  2. 2.Department of Human GeneticsLeiden University Medical CenterLeidenThe Netherlands

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