autoinflammatory disease, multisystem, with immune dysregulation, X-linked

Autoinflammatory disease, multisystem, with immune dysregulation, X-linked is a condition that affects multiple organ systems, including the immune, cardiac, and respiratory systems. It is linked to alterations in the DOCK11 gene, which is involved in immune regulation. Because the condition follows an X-linked inheritance pattern, males are primarily affected while females may experience milder manifestations due to skewed X-inactivation. Although precise prevalence data are not available, the condition is recognized as uncommon.

The clinical presentation is multisystem in nature. Characteristically, all affected individuals display a thickened nuchal skin fold, hypotonia, pericarditis, and a restrictive ventilatory defect, which often prompt early clinical evaluation. Additionally, a subset of individuals may experience signs of immune dysregulation such as increased total leukocyte counts, altered immunoglobulin levels (with decreased circulating IgA and increased circulating IgE), and autoimmune hemolytic anemia. Gastrointestinal issues including recurrent gastroenteritis and failure to thrive, along with occasional musculoskeletal complaints such as polyarticular arthritis, further underscore the variable presentation of this condition. Not all individuals experience every feature, and severity varies considerably.

This condition is associated with pathogenic variants in the DOCK11 gene, which plays a role in regulating immune responses. It is inherited in an X-linked pattern, meaning that males, with a single X chromosome, are most often affected while females may have milder symptoms due to variable X-inactivation. Families are encouraged to seek genetic counseling to better understand the inheritance pattern, implications for family planning, and the potential for variable symptoms among affected individuals.

Currently, management focuses on supportive care and symptom relief as there are no treatments specifically approved for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary approach that may include specialists in immunology, cardiology, pulmonology, and rheumatology. Long-term management includes regular surveillance to monitor cardiac, respiratory, and immune-related complications. Genetic counseling is recommended to provide further guidance about inheritance and family planning, and patients should discuss available supportive options with their healthcare team to determine the best strategy for their specific situation.

Outcomes vary widely among individuals, with the disease course being influenced by the severity of multisystem involvement and the quality of supportive care received. With current standards of care, many individuals benefit from individualized management plans, and outcomes described in medical literature continue to evolve as standards of care improve. The condition may remain stable for some patients while others experience challenges related to progressive complications. Families often find it helpful to connect with specialists familiar with this condition as well as genetic counselors, who can provide guidance on managing the lifelong aspects of this disorder.