Clinical immunology in chromatinopathies: a scoping review

Chromatinopathies (CP) are a subclass of monogenic neurodevelopmental disorders caused by germline mutations in genes involved in epigenetic regulation. Symptoms may include neurodevelopmental delay, intellectual disability, autism spectrum disorder, facial dysmorphisms, growth abnormalities, and various congenital anomalies. These disorders often also present with immunopathology. However, a clear insight into immune dysregulation in CPs is currently unavailable.

This scoping review aims to synthesize clinical data on anomalies of the immune system, including laboratory values and medical history of individuals with CPs, to fill knowledge gaps.

Articles on immunological aspects in individuals with CPs, caused by germline mutations affecting chromatin-modifying enzymes from the "writers" group, were included. Searches were conducted using PubMed, Cochrane Library, and Web of Science until March 30, 2024 and articles after that date were added as cross-referenced.

101 articles covering 715 individuals with 21 different syndromes were included. In all CPs, frequent infections, mainly of the respiratory tract, were reported. Moreover, common immunopathology included immunodeficiency and immune thrombocytopenic purpura. Immunologic laboratory results were available for a total of 183 individuals with ten different syndromes. Hypo/a-gammaglobulinemia was present in the majority of these individuals. The most characterized and affected syndromes were ICF syndrome type 1 and Kabuki syndrome type 1.

Despite common immune manifestations, systematic laboratory tests on immune characteristics are not commonly performed for the majority of CP cases. To better understand the role of immune dysfunction in the pathology of CPs and offer treatment strategies, standardized guidelines for clinicians need to be established.

https://inplasy.com/wp-content/uploads/2025/12/INPLASY-Protocol-8609.pdf, identifier INPLASY2025120066.