STAT1 gain-of-function (GOF) mutations are associated with a rare autosomal dominant immunodeficiency disorder with main clinical manifestations including chronic mucocutaneous candidiasis (CMC) and bronchiectasis. In addition, these patients show higher incidences of cerebral and extracerebral aneurysm, malignancies and various autoimmune conditions compared to the general population. Although previous publications have reported clinical findings in patients with STAT1 GOF mutation, they did not include histopathologic features. Herein, we describe the first case with detailed histologic findings in the lung of a 5-year-old patient with a de novo STAT1 GOF mutation, who presented with CMC and bronchiectasis. The biopsy showed severe bronchiolectasis with extensive airway dilatation and occasional disruptions. Peribronchiolar inflammation was not always present and evident mainly in areas of airway disruption; inflammation may have not been a main driver of the airway damage in this case. The airway dilatation often showed an interesting herniating pattern, possibly implying a connective tissue etiology. This case also demonstrates the diagnostic utility of whole exome sequencing as STAT1 GOF mutations are not detected by routine workup. The definitive diagnosis will lead to more specific treatments and increased surveillance for serious conditions, such as cerebral aneurysms and malignancies.
- gain of function mutation
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Pathology and Forensic Medicine