Chromosome 22q11.2 Deletion Syndrome: A Comprehensive Review of Molecular Genetics in the Context of Multidisciplinary Clinical Approach.

The 22q11.2 deletion syndrome is a multisystemic disorder characterized by a marked variability of phenotypic features, making the diagnosis challenging for clinicians. The wide spectrum of clinical manifestations includes congenital heart defects-most frequently conotruncal cardiac anomalies-thymic hypoplasia and predominating cellular immune deficiency, laryngeal developmental defects, midline anomalies with cleft palate and velar insufficiency, structural airway defects, facial dysmorphism, parathyroid and thyroid gland hormonal dysfunctions, speech delay, developmental delay, and neurocognitive and psychiatric disorders.

Infections and immune dysregulation in ataxia-telangiectasia children with hyper-IgM and non-hyper-IgM phenotypes: A single-center experience.

Ataxia-telangiectasia (A-T) is a severe syndromic neurodegenerative inborn error of immunity characterized by DNA reparation defect, chromosomal instability, and hypersensitivity to ionizing radiation, thereby predisposing affected individuals to malignant transformation. While the leading disease symptomatology is associated with progressively debilitating cerebellar ataxia accompanied by central and peripheral nervous system dysfunctions, A-T is a multisystemic disorder manifesting with the heterogeneity of phenotypic features. These include airway and interstitial lung disease, chronic liver disease, endocrine abnormalities, and cutaneous and deep-organ granulomatosis.

Clinical and immunological assessment of APDS2 with features of the SHORT syndrome related to a novel mutation in with reduced penetrance.

Monoallelic loss-of-function (LOF) mutations in the phosphatidylinositol 3-kinase () gene affecting the inter-Src homology 2 domain of the p85α regulatory subunit of phosphoinositide--3-kinase δ (PI3Kδ) cause the activated PI3K δ syndrome (APDS2). APDS2 is defined as a primary antibody deficiency, developmental abnormalities within the B and T lymph cell compartments, and immune dysregulation. The genetic defect of APDS2 is shared with that of the SHORT syndrome, characterized by short stature, joint hyperextensibility, ocular depression, Rieger anomaly, and delayed tooth eruption.

Immune Dysregulation in Pediatric Common Variable Immunodeficiency: Implications for the Diagnostic Approach.

Infections and infectious complications are hallmarks of common variable immunodeficiency (CVID) and the leading cause of morbidity and mortality in affected patients at any age. However, the pediatric CVID is no longer perceived as a primary immunodeficiency associated solely with infectious manifestations; autoimmune, allergic, lymphoproliferative, and malignant disorders and organ-specific immunopathology also characterize the spectrum of non-infectious complications. In this study, we sought to determine the role of immune dysregulation and frequency of non-infectious sequelae in children affected with CVID.

Case Report: Autoimmune Lymphoproliferative Syndrome vs. Chronic Active Epstein-Barr Virus Infection in Children: A Diagnostic Challenge.

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder characterized by a disruption of the lymphocyte apoptosis pathway, self-tolerance, and immune system homeostasis. Defects in genes within the first apoptosis signal (FAS)-mediated pathway cause an expansion of autoreactive double-negative T cells leading to non-malignant lymphoproliferation, autoimmune disorders, and an increased risk of lymphoma. The aim of the study was to show the diagnostic dilemmas and difficulties in the process of recognizing ALPS in the light of chronic active Epstein-Barr virus (CAEBV) infection.

The pediatric common variable immunodeficiency - from genetics to therapy: a review.

Unlabelled: Common variable immunodeficiency (CVID) is the most prevalent antibody deficiency, characterized by remarkable genetic, immunological, and clinical heterogeneity. The diagnosis of pediatric CVID is challenging due to the immaturity of the immune response and sustained actively developing antibody affinity to antigens and immunological memory that may overlap with the inborn error of immunity. Significant progress has been recently done in the field of immunogenetics, yet a paucity of experimental and clinical studies on different systemic manifestations and immunological features of CVID in children may contribute to a delayed diagnosis and therapy.