Primary immunodeficiency in a patient with Kabuki syndrome

Abstract

Kabuki syndrome is a well-known disease characterized by postnatal growth failure, dysmorphic facial features, skeletal abnormalities, and mental retardation associated with one of the pathogenic mutations in the KMT2D or KDM6A genes. At least 50% of individuals with Kabuki syndrome tend to develop recurrent infections and immune abnormalities, primarily hypogammaglobulinemia. The article describes the clinical course of resistant infectious syndrome in an 18-month-old child without typical dysmorphic and dermatoglyphic manifestations characteristic of Kabuki syndrome. A long history of resistant bacterial infection, enterocolitis, microcephaly, autistic-like behavior, hyperkinetic disorder, CT scan patterns of granulomatous lymphocytic interstitial lung disease (GLILD), suggested the immunodeficiency as part of a hereditary genetically determined syndrome. At the same time, the patient did not experience hypogammaglobulinemia characteristic of Kabuki syndrome. The upper normal response to previously received vaccination and a polyclonal repertoire of B-lymphocytes indicated the absence of disturbances in the humoral immunity. Immunophenotyping revealed the absence of T-regulatory cells (CD4+CD25++CD127–) as well as effector NK cells (CD16+CD56+CD3–) in the peripheral blood. The significant reduction of CD4+CD3+ T-lymphocytes and CD4+/CD8+ index was observed. In addition, no expression of integrin-beta (CD18) on neutrophils revealed.Conclusion. In children under the age of 2, Kabuki syndrome may present difficulties for clinical diagnosis due to the absence of distinctive phenotypic signs. Patients with mental disorders, congenital malformations, recurrent infections suspected of immunodeficiency should be carried out using molecular genetic exploration, including testing for mutations in the KMT2D and KDM6A.