LAUSR

Abstract Background: Kabuki syndrome (KS) is a genetically heterogeneous disorder characterized by striking facial features similar to make-up of actors in Japanese Kabuki performance together with multi-organ defects. The first identified and most frequently involved gene is KMT2D which encodes a histone H3K4 methyltransferase. Even though KS is a rare syndrome and associated diabetes has been rarely reported, both type 1 DM and type 2 DM had been previously reported. Understanding the function of the genes that lead to KS opens up the possibility of targeted therapies for diabetes. Clinical Case: A 27-year-old male with unconfirmed diagnosis of Fragile X syndrome since childhood came to attend our diabetes clinic due to uncontrolled hyperglycemia (A1C 8.5%). He was a preterm baby born at 7 months and had been clinically diagnosed with Fragile X syndrome due to delayed development and moderate mental retardation from another hospital. At the age of 11 months, he underwent right nephrectomy from severe hydronephrosis. He later developed hypertension due to coarctation of aorta at the age of 14. At the age of 19, he presented with polyuria and lost 10 kilograms within 6 months (baseline BMI at 26.3 kg/m2). Laboratory data showed A1C 14.7%, plasma glucose 432 mg/dL, no ketonemia. At that time, youth-onset type 2 DM had been diagnosed and insulin treatment had been given for a few months before switching to oral medications. He presented at our hospital at the age of 27. Based on his facial features and multi-organ involvements, KS was clinically suspected and then was confirmed to have heterozygous frameshift deletion mutation (c.7524 deletion) of the KMT2D gene. Evaluation of beta-cell function revealed preserved beta-cell with stimulated C-peptide at 8.7 ng/mL. HOMA-IR score suggested severe insulin resistance (HOMA-IR 5.5). Pancreatic auto-antibodies revealed negative results. Currently, his diabetes has been fairly controlled (A1C varied from 6.8–8.5%). Conclusions: Our case highlights the importance of clinical recognizable phenotype in patients with diabetes. To study and decipher mechanistic studies of the role of epigenetic regulations in this syndrome toward insulin signaling pathways would provide an opportunity for novel insights into pathogenesis of epigenetic defects in Kabuki syndrome.