Kabuki Syndrome and Its Association with Arthritis and Hematological Conditions
Kabuki syndrome is associated with both arthritis and various hematological conditions, with autoimmune manifestations being particularly common, affecting approximately 13.6% of patients and up to 25.6% of adults with the syndrome.
Arthritis in Kabuki Syndrome
Arthritis is not a primary feature of Kabuki syndrome, but it can occur as part of the autoimmune manifestations associated with the condition:
- Autoimmune disorders are frequently observed in patients with Kabuki syndrome, with joint involvement being one of the possible manifestations 1, 2
- Unlike Kawasaki disease (which is a different condition), where arthritis or arthralgia commonly occurs in the first week of illness and involves multiple joints including small interphalangeal joints and large weight-bearing joints, Kabuki syndrome's joint involvement is primarily autoimmune in nature 3
Hematological Manifestations in Kabuki Syndrome
Kabuki syndrome is strongly associated with various hematological abnormalities, particularly:
- Immune thrombocytopenic purpura (ITP) affects approximately 7.3% of Kabuki syndrome patients, making it the most common autoimmune manifestation 2
- Autoimmune hemolytic anemia occurs in about 4.0% of patients with Kabuki syndrome 2, 4
- Some patients experience both ITP and hemolytic anemia concurrently, suggesting a broader autoimmune dysregulation 4
- Patients with missense variants in causative genes have a higher frequency of immune thrombocytopenic purpura compared to those with other types of variants (p = 0.027) 2
Immunological Abnormalities in Kabuki Syndrome
The immunological profile of Kabuki syndrome includes:
- Hypogammaglobulinemia affects 58.2% of patients, with decreased IgA levels being particularly common (found in 79% of patients in one study) 2, 5
- Low IgG levels are observed in 42-45% of patients 6, 5
- Low IgM levels are less frequently observed, affecting about 14% of patients 6
- The pattern of antibody abnormalities resembles common variable immune deficiency (CVID) 5
- Increased susceptibility to infections is reported in 44.1-69% of patients 2, 6
Autoimmune Manifestations Beyond Hematological Issues
- Vitiligo is a frequent non-hematological autoimmune manifestation in Kabuki syndrome 1, 2, 4
- Autoimmune thyroiditis has been reported in some patients 1
- Multiple autoimmune disease manifestations (≥2) occur in 5.6% of patients 2
Risk Factors and Associations
- Thymectomy is significantly correlated with autoimmune cytopenia in Kabuki syndrome patients (p < 0.002) 6
- Elevated CD3+ TCRαβ+ CD4-CD8- T-cells are present in 23% of individuals and correlate with hematological and overall autoimmunity (p < 0.05) 6
- Congenital heart defects are common (49% of patients) but not significantly correlated with autoimmune manifestations 6
Management Considerations
- Immunological evaluation is recommended at the time of diagnosis for all children with Kabuki syndrome to reduce preventable morbidity and mortality 5
- Mycophenolate has shown complete response as a long-term immunomodulatory treatment in patients with autoimmune cytopenias 6
- Immunoglobulin substitution therapy may be required in patients with significant antibody deficiency 6
- Patients with autoimmune conditions may experience a chronic and relapsing course, requiring ongoing monitoring 4
The immunological and autoimmune manifestations in Kabuki syndrome are likely related to the epigenetic dysregulation caused by mutations in KMT2D and KDM6A genes, which affect immune system development and regulation 1, 2.