Immune dysregulation in Kabuki syndrome: a case report

Background and Aims: A 23-year-old woman, clinically diagnosed with Kabuki Syndrome (KS) and Evans Syndrome (ES) was referred to our Pediatric Department for corticosteroid-induced diabetes onset. The patient underwent several courses of corticosteroids due to ES relapses and presented with recurrent respiratory infections. Methods: When admitted to our hospital, the patient presented with peculiar KS clinical feature and clinical sideeffects of systemic glucocorticoids therapy. Splenomegaly and signs of chronic lung inflammation and interstitial lung disease were also described at HRTC. An immunological study was performed highlighting severe hypogammaglobulinemia (IgG= 200 mg/dl, IgA= 2 mg/dl and IgM= 149 mg/dl). Nonsense variant in the KMT2D (NM_003482.3) gene: c.8974G>T, p.Glu2992Ter was detected. Supportive treatment with amoxicillin/clavulanate prophylaxis and facilitated subcutaneous immunoglobulin replacement was immediately started. Six months later, no infections were reported. Conversely, ITP had partially been responsive to high-dose prednisone treatment. Alternative therapies, including Rituximab have been considered. Results: KS is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. Failure of both B-cell development and autoreactive immune cells suppression leads to immunodeficiency and autoimmunity that, however, may be undiagnosed for long time. Our patient’s case is paradigmatic, since she presented, years after disease onset, with iatrogenic morbidity and severe lung disease. Conclusions: This case emphasizes the importance of suspecting immune-dysregulation in KS patients. It also highlights the need to perform immunologic evaluations at the time of both KS diagnosis and during disease follow up in order to allow proper treatment while avoiding preventable morbidity in these patients.