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WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome is a rare primary immunodeficiency disorder characterized by susceptibility to human papillomavirus (HPV) infections, neutropenia, and hypogammaglobulinemia. WHIM syndrome is caused by a gain-of-function mutation CXCR4, leading to increased responsiveness of neutrophils and lymphocytes to CXCL12. This results in an accumulation of atypical hypersegmented mature neutrophils in the bone marrow and peripheral blood neutropenia. This case report discusses a 10-year-old girl who was diagnosed with WHIM syndrome at the age of four years following Haemophilus influenzae meningitis. She was found to have Tetralogy of Fallot at birth, which was surgically repaired when she was one year old. She was also found to have significant neutropenia during surgery and received multiple doses of G-CSF with a good response. She presented to the hospital at the age of four years with fever, neck stiffness, lethargy, and headache and was diagnosed with H. influenzae meningitis. Her immunology workup revealed significant neutropenia and hypogammaglobulinemia, as well as low antibody levels to H. influenza type B, tetanus toxoid, and Streptococcus pneumonia, despite up-to-date vaccination. Furthermore, decreased levels of T cells and B cells were detected. The patient was started on IgG replacement therapy and Bactrim prophylaxis. Bone marrow biopsy revealed granulocytic hyperplasia and occasional hypersegmented neutrophils, suggesting myelokathexis. Genetic testing revealed a heterozygous CXCR4 mutation with a premature stop codon (p.Ser338Ter), confirming the diagnosis of WHIM syndrome. This case report highlights the association of WHIM syndrome with congenital heart defects, such as Tetralogy of Fallot. A literature review revealed three other cases of congenital heart defects in patients with WHIM syndrome, indicating a potential role for CXCR4 and CXCL12 in septum formation. The rarity of the disorder and the lack of a universal screening tool makes the diagnosis of WHIM syndrome difficult. Therefore, physicians should consider WHIM syndrome in patients with congenital heart defects, particularly if they have recurrent HPV infections, neutropenia, and hypogammaglobulinemia.

Otoferlin mRNA expression is increased in JDM patients’ PBMCs and muscle compared to healthy controls. This study aims to evaluate the role of otoferlin in JDM disease pathophysiology and its association with disease activity in untreated children with JDM. A total of 26 untreated JDM (88.5% female, 92.3% white, non-Hispanic) and 15 healthy controls were included in this study. Otoferlin mRNA expression was determined by qRT-PCR before and a few months after therapy. Detailed flow cytometry of various cell surface markers and cytoplasmic otoferlin was performed to identify cells expressing otoferlin. In addition, muscle otoferlin expression was evaluated in situ in six untreated JDM patients and three healthy controls. There was a significant increase in otoferlin expression in JDM children compared to controls (Median 67.5 vs. 2.1; p = 0.001). There was a positive correlation between mRNA otoferlin expression and the following disease activity markers: disease activity scores (DAS)-total (rs = 0.62, p < 0.001); childhood myositis assessment scale (CMAS) (rs = −0.61, p = 0.002); neopterin (rs = 0.57, p = 0.004) and von Willebrand factor antigen (vWF: Ag) (rs = 0.60, p = 0.004). Most of the otoferlin-positive cells were unswitched B cells (63–99.4%), with 65–75% of them expressing plasmablast markers (CD19+, IgM+, CD38hi, CD24−). The findings of this pilot study suggest that otoferlin expression is associated with muscle weakness, making it a possible biomarker of disease activity. Additionally, B cells and plasmablasts were the primary cells expressing otoferlin.

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