A novel IKZF1 variant in a family with autosomal dominant CVID: A case for expanding exon coverage in inborn errors of immunity.

Common variable immune deficiency (CVID) is a heterogenous group of disorders characterized by varying degrees of hypogammaglobulinemia, recurrent infections, and autoimmunity. Currently, pathogenic variants are identified in approximately 20-30% of CVID cases. Here we report a 3-generation family with autosomal dominant Common Variable Immunodeficiency (CVID) diagnosed in 9 affected individuals. Although primary immune deficiency panels and exome sequencing were non-diagnostic, whole genome sequencing revealed a novel, pathogenic c.499C > T: p.His167Tyr variant in IKZF1, a critical regulator of B cell development. Functional testing done through pericentromeric heterochromatin localization and light shift chemiluminescent electrophoretic mobility shift assay confirmed the variant's deleterious effect via a haploinsufficiency mechanism. Our findings expand the spectrum of known IKZF1 mutations and contribute to a more comprehensive understanding of CVID's genetic heterogeneity. Furthermore, this case underscores the importance of considering whole genome sequencing for comprehensive genetic diagnosis when concern for a monogenic inborn errors of immunity is high.

An unusual presentation of chronic recurrent multifocal osteomyelitis involving bones of the skull.

Chronic recurrent multifocal osteomyelitis is a rare, multisystemic inflammatory disease that affects children and adolescents. We present the case of an African-American adolescent male who presented with recurrent swelling of the temporal region with skull involvement on head imaging, which is atypical for chronic recurrent multifocal osteomyelitis. He had clinical and laboratory improvement after initiation of indomethacin and pamidronate.

Prolonged Hospitalization in a Pediatric Patient With Multisystem Inflammatory Syndrome (MIS-C) and Human Rhino-Enterovirus Infection: A Case Report.

Multisystem inflammatory syndrome in children (MIS-C) is a serious sequela of acute SARS-CoV-2 infection. It is unclear whether the co-occurrence of other viral respiratory illnesses, such as the human rhino-enterovirus (HRV/ENT), prolongs hospitalization or affects the clinical phenotype of patients with MIS-C. We report the hospital course of a three-year-old with MIS-C and HRV/ENT infection, who tested positive for HRV/ENT infection a few days prior to re-presenting for six days of fever, one day of emesis, bilateral conjunctivitis, and shortness of breath, all consistent with MIS-C. Due to worsening hypotension, he was admitted to a pediatric intensive care unit (ICU) at a tertiary center, where he received vasoactive support, intravenous immunoglobulin, and high-dose intravenous steroids. Because of his worsening respiratory status, he was also started on anakinra with resultant gradual improvement. He was hospitalized for a total of 15 days. Concurrence of other viral infections may prolong hospitalization for patients with MIS-C.