Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia
Kabuki syndrome (KS) is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. The syndrome is characterized by anomalies in multiple organ systems, and it is associated with autoimmune and infl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1087002/full |
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| author | Lucia Leonardi Alessia Testa Mariavittoria Feleppa Roberto Paparella Francesca Conti Antonio Marzollo Alberto Spalice Fiorina Giona Maria Gnazzo Gian Marco Andreoli Francesco Costantino Luigi Tarani |
| author_facet | Lucia Leonardi Alessia Testa Mariavittoria Feleppa Roberto Paparella Francesca Conti Antonio Marzollo Alberto Spalice Fiorina Giona Maria Gnazzo Gian Marco Andreoli Francesco Costantino Luigi Tarani |
| author_sort | Lucia Leonardi |
| collection | DOAJ |
| description | Kabuki syndrome (KS) is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. The syndrome is characterized by anomalies in multiple organ systems, and it is associated with autoimmune and inflammatory disorders, and an underlying immunological phenotype characterized by immunodeficiency and immune dysregulation. Up to 17% of KS patients present with immune thrombocytopenia characterized by a severe, chronic or relapsing course, and often associated to other hematological autoimmune diseases including autoimmune hemolytic anemia, eventually resulting in Evans syndrome (ES). A 23-year-old woman, clinically diagnosed with KS and presenting from the age of 3 years with ES was referred to the Rare Diseases Centre of our Pediatric Department for corticosteroid-induced hyperglycemia. Several ES relapses and recurrent respiratory infections in the previous years were reported. Severe hypogammaglobulinemia, splenomegaly and signs of chronic lung inflammation were diagnosed only at the time of our observation. Supportive treatment with amoxicillin-clavulanate prophylaxis and recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin replacement were immediately started. In KS patients, the failure of B-cell development and the lack of autoreactive immune cells suppression can lead to immunodeficiency and autoimmunity that may be undiagnosed for a long time. Our patient's case is paradigmatic since she presented with preventable morbidity and severe lung disease years after disease onset. This case emphasizes the importance of suspecting immune dysregulation in KS. Pathogenesis and immunological complications of KS are discussed. Moreover, the need to perform immunologic evaluations is highlighted both at the time of KS diagnosis and during disease follow-up, in order to allow proper treatment while intercepting avoidable morbidity in these patients. |
| first_indexed | 2024-03-13T06:36:10Z |
| format | Article |
| id | doaj.art-9152f9658be14a77953af50b9fbafcd2 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-03-13T06:36:10Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-9152f9658be14a77953af50b9fbafcd22023-06-09T04:29:43ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-06-011110.3389/fped.2023.10870021087002Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemiaLucia Leonardi0Alessia Testa1Mariavittoria Feleppa2Roberto Paparella3Francesca Conti4Antonio Marzollo5Alberto Spalice6Fiorina Giona7Maria Gnazzo8Gian Marco Andreoli9Francesco Costantino10Luigi Tarani11Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyPediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyPediatric Hematology, Oncology and Stem Cell Transplant Division, Padua University Hospital, Padua, ItalyDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Translational and Precision Medicine, Sapienza University of Rome, Rome, ItalyTranslational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, ItalyKabuki syndrome (KS) is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. The syndrome is characterized by anomalies in multiple organ systems, and it is associated with autoimmune and inflammatory disorders, and an underlying immunological phenotype characterized by immunodeficiency and immune dysregulation. Up to 17% of KS patients present with immune thrombocytopenia characterized by a severe, chronic or relapsing course, and often associated to other hematological autoimmune diseases including autoimmune hemolytic anemia, eventually resulting in Evans syndrome (ES). A 23-year-old woman, clinically diagnosed with KS and presenting from the age of 3 years with ES was referred to the Rare Diseases Centre of our Pediatric Department for corticosteroid-induced hyperglycemia. Several ES relapses and recurrent respiratory infections in the previous years were reported. Severe hypogammaglobulinemia, splenomegaly and signs of chronic lung inflammation were diagnosed only at the time of our observation. Supportive treatment with amoxicillin-clavulanate prophylaxis and recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin replacement were immediately started. In KS patients, the failure of B-cell development and the lack of autoreactive immune cells suppression can lead to immunodeficiency and autoimmunity that may be undiagnosed for a long time. Our patient's case is paradigmatic since she presented with preventable morbidity and severe lung disease years after disease onset. This case emphasizes the importance of suspecting immune dysregulation in KS. Pathogenesis and immunological complications of KS are discussed. Moreover, the need to perform immunologic evaluations is highlighted both at the time of KS diagnosis and during disease follow-up, in order to allow proper treatment while intercepting avoidable morbidity in these patients.https://www.frontiersin.org/articles/10.3389/fped.2023.1087002/fullKabuki syndromeEvans syndromeautoimmunityimmunodeficiencyhypogammaglobulinemiaimmune dysregulation |
| spellingShingle | Lucia Leonardi Alessia Testa Mariavittoria Feleppa Roberto Paparella Francesca Conti Antonio Marzollo Alberto Spalice Fiorina Giona Maria Gnazzo Gian Marco Andreoli Francesco Costantino Luigi Tarani Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia Frontiers in Pediatrics Kabuki syndrome Evans syndrome autoimmunity immunodeficiency hypogammaglobulinemia immune dysregulation |
| title | Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia |
| title_full | Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia |
| title_fullStr | Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia |
| title_full_unstemmed | Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia |
| title_short | Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia |
| title_sort | immune dysregulation in kabuki syndrome a case report of evans syndrome and hypogammaglobulinemia |
| topic | Kabuki syndrome Evans syndrome autoimmunity immunodeficiency hypogammaglobulinemia immune dysregulation |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1087002/full |
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