Syndromic immunodeficiencies: a pediatrician’s perspective on selected diseases

Abstract

Background: Syndromic immunodeficiencies are a genetically and pathophysiologically heterogeneous group of inborn errors of immunity. These are characterized by multiple extra immune clinical symptoms and a wide range of immunological phenotypes with increased susceptibility to infections, autoimmune phenomena, immune dysregulation, organ-specificpathology, and malignancy.Objective: To increase the pediatricians’ awareness of this multifaceted group of primary immunodeficiencies in children.Methods: A comprehensive review of genetic background and clinical symptomatology of syndromic immunodeficiencies as well as current diagnostic approach and treatment modalities.Results: From the pediatrician’s perspective, an early-life diagnosis of syndromic immunodeficiencies, which is frequently indispensable for successful life-saving immunocorrection, poses a diagnostic challenge. Increased pediatricians’ awareness to recognize signs and symptoms of these diseases in affected children is of paramount importance. Current advances in molecular  biotechnology and immunogenetics, resulting in the implementation of newborn screening and new-generation sequencing, provide informative tools for definitive diagnosis and, in many new disease entities, for their definition and genotype–phenotype delineation and correlation.Conclusions: A broad spectrum of clinical phenotypes in children with syndromic primary immunodeficiencies requires pediatrician’s special attention, that is, individualized multidisciplinary approach under the supervision of a clinical immunologist.