Combined Immunodeficiency Associated With MAP2K1 p.Tyr130His Variant in Cardiofaciocutaneous Syndrome: A Case Report With Literature-Based Phenotypic Comparison

Scritto il 18/02/2026
da Şefika İlknur Kökcü Karadağ

Scand J Immunol. 2026 Feb;103(2):e70101. doi: 10.1111/sji.70101.

ABSTRACT

Cardiofaciocutaneous syndrome (CFCS) is a RASopathy involving craniofacial, cardiac, cutaneous, and neurologic features. MAP2K1 mutations, particularly in the kinase domain, are linked to CFCS type 3. Immune dysfunction has not previously been reported with the p.Tyr130His variant. To describe the case of combined immunodeficiency (CID) associated with the MAP2K1 p.Tyr130His variant. A 4-month-old female with CFCS presented with recurrent infections, growth failure, and ectodermal findings. Immunologic workup revealed hypogammaglobulinemia, low T cell subsets, and absent vaccine responses. Genetic analysis identified the MAP2K1 p.Tyr130His variant. She was started on intravenous immunoglobulin and prophylaxis, with clinical improvement. We describe a case of CID associated with the MAP2K1 p.Tyr130His variant adding to the growing evidence of immune dysregulation in CFCS.

PMID:41708578 | DOI:10.1111/sji.70101