Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is a primary immunodeficiency disorder that affects the immune system, blood, and skin. It is caused by mutations in the WAS gene and is inherited in an X-linked manner, predominantly impacting males while female carriers may experience milder symptoms. Patients typically present with eczematous skin changes, thrombocytopenia with decreased platelet volume, and recurrent infections, along with an increased risk for autoimmune manifestations and malignancies. This condition is rare, affecting between 1 and 9 per million people.

The clinical features of Wiskott-Aldrich syndrome are marked by persistently inflamed, eczematoid dermatitis and consistently low platelet counts accompanied by reduced mean platelet volume. Nearly all affected individuals display abnormal natural killer cell physiology, while many also have elevated IgE levels and experience recurrent infections such as otitis media, pneumonia, and sinusitis. Other manifestations, including decreased levels of immunoglobulins, autoimmune hemolytic anemia, ulcerative colitis, and lymphoproliferative disorders, occur in a subset of patients. Not all individuals experience every feature, and severity varies considerably.

Wiskott-Aldrich syndrome results from pathogenic variants in the WAS gene, which plays a critical role in immune system regulation and platelet formation. It is inherited in an X-linked manner, meaning that males are typically affected while female carriers may show mild symptoms due to variable X-inactivation. Families are encouraged to seek genetic counseling to help understand the inheritance pattern and the implications for family planning.

Currently, management of Wiskott-Aldrich syndrome focuses on supportive care and symptom management because no treatments are specifically approved for this condition. A multidisciplinary team is important to address the various complications, and regular surveillance is an essential part of long-term care to monitor for infections, bleeding events, and autoimmune issues. Patients are advised to discuss all available options, including investigational therapies under orphan drug designation, with their healthcare team, and genetic counseling is recommended to guide family planning.

The outlook for individuals with Wiskott-Aldrich syndrome varies widely, with outcomes influenced by symptom severity, age at diagnosis, and access to specialized care. Many patients benefit from modern supportive treatments, and with the improvements in multidisciplinary management, many affected individuals are able to live into adulthood. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists and genetic counselors for ongoing guidance and support.

Several clinical trials are currently investigating new treatment approaches for Wiskott-Aldrich syndrome. Individuals interested in exploring clinical trial options can search ClinicalTrials.gov or discuss eligibility with their care team.