This three-sibling case series of genetically confirmed DOCK8 deficiency highlights severe multisystem involvement and risk of irreversible organ damage, including a fatal venous thromboembolism, and underscores the importance of early diagnosis and timely planning of hematopoietic stem cell transplantation (HSCT) as the only curative approach.
Three siblings with genetically confirmed DOCK8 deficiency all showed early-onset atopic dermatitis, recurrent respiratory tract infections, and failure to thrive.
Bronchiectasis and severe viral infections were observed in all three siblings.
Ocular involvement developed in two of the three patients, causing irreversible damage.
One patient developed iatrogenic Cushing syndrome due to prolonged topical corticosteroid use.
In the patient with iatrogenic Cushing syndrome, catheter-related superficial thrombophlebitis progressed to deep vein thrombosis and cerebral venous sinus thrombosis, with a fatal outcome complicated by probable pulmonary thromboembolism.
The authors conclude that DOCK8 deficiency carries risk of severe multisystem involvement and irreversible organ damage, and that early diagnosis and timely HSCT planning are critical.
This report describes three siblings with DOCK8 deficiency, a rare inherited immune disorder that causes eczema, repeated infections, and a higher risk of cancer. All three children had early skin disease, repeated respiratory infections, poor growth, bronchiectasis (damaged airways), and severe viral infections. Two of the siblings had serious eye problems. One lost vision permanently from CMV infection of the retina, and another had a perforated cornea after a herpesvirus infection. One sibling developed Cushing syndrome from long-term use of steroid creams. This same patient developed a blood clot at a catheter site that spread to deep veins and the brain's venous sinuses, and died, probably with a clot in the lungs as well. This research suggests that DOCK8 deficiency can cause serious and sometimes irreversible damage across many organs, and that the course can differ even among siblings. The authors emphasize early diagnosis and timely planning of stem cell transplantation, the only curative treatment. As a small case series of three patients, it cannot show how often these complications occur.
Köse Özcan &, Yırgın K, Sert A, Arslan S, Özkan Y, Celiksoy M. (2026). "Fatal venous thromboembolism and divergent phenotypes in DOCK8 deficiency: a three-sibling case series".. Immunologic research. https://doi.org/10.1007/s12026-026-09866-z