Bone Marrow Failure as an Underrecognized Feature of KAT6A Syndrome

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• KAT6A syndrome is a rare genetic disorder caused by pathogenic variants in the KAT6A gene.
• While neurodevelopmental issues are recognized, hematologic manifestations are often overlooked.
• The KAT6A gene encodes a histone acetyltransferase crucial for chromatin remodeling and hematopoietic stem cell function.

Purpose of the Study:

• To highlight the underrecognized hematologic manifestations of KAT6A syndrome.
• To present successful treatment of severe bone marrow failure in KAT6A syndrome patients with hematopoietic stem cell transplantation.
• To review the literature for additional cases of cytopenias associated with KAT6A syndrome.

Main Methods:

• Case report of two pediatric patients with KAT6A syndrome and severe bone marrow failure.
• Genetic analysis identifying pathogenic variants in KAT6A.
• Hematopoietic stem cell transplantation as a treatment modality.
• Comprehensive literature review of KAT6A syndrome and associated cytopenias.

Main Results:

• Two pediatric patients presented with severe bone marrow failure due to distinct pathogenic variants in KAT6A.
• Both patients achieved successful engraftment and recovery following hematopoietic stem cell transplantation.
• Literature review identified additional cases of cytopenias in patients with KAT6A syndrome.

Conclusions:

• Bone marrow failure is a significant and underrecognized hematologic feature of KAT6A syndrome.
• Hematopoietic stem cell transplantation is a viable and effective treatment for severe bone marrow failure in KAT6A syndrome.
• Increased awareness and investigation of hematologic abnormalities are crucial for diagnosing and managing KAT6A syndrome.