A Sherlock Approach to a Kindred With a Variable Immunohematologic Phenotype

Given the ubiquity of leukopenia and sinopulmonary infections in childhood, differentiating patients with inborn errors of immunity (IEI) from otherwise healthy patients can be challenging. The diagnostic complexity is further exacerbated in disorders with wide phenotypic variability such as warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome. However, using a Sherlock approach with careful attention to details in the patient's medical history and physical examination coupled with a comprehensive family history can heighten the index of suspicion for underlying IEI. Subsequent iterative and deductive reasoning incorporating results from laboratory interrogation, response (or lack thereof) to standard therapy, and emergence of new symptoms can further aid in a timely diagnosis of IEI. Herein, we detail a WHIM syndrome kindred with marked phenotype variability, identified after the presentation of a child with intermittent neutropenia and sinopulmonary infections. The complexity of this kindred highlights the utility of an interspecialty, collaborative Sherlock approach to diagnosis, and care. In addition, the genetic underpinnings, diagnostic approaches, clinical features, supportive care options, and management of WHIM syndrome are reviewed.