Hyperinsulinemia in kabuki syndrome: a case with partial deletion of KMT2D gene

Introduction: Kabuki syndrome (KS1 OMIM 147920) genetically is an autosomal dominant rare disorder and clinically is heterogeneous congenital malformation syndrome (1, 2). Hyperinsulinism is conceived to be a rare manifestation Of Kabuki syndrome (3). Congenital hyperinsulinism (CHI - MIM 256450) is characterized by persistent hypoglycemia due to defective of upregulation of insulin secretion. Herein we present a case with clinical and biological evidences of CHI. Our male patient was diagnosed with persistent hyperinsulinism and hypoglycemia at the age 26 months.Materials & Methods: Analysis of the coding regions and exon/intron boundaries of the KCNJ11, ABCC8, AKT2, GLUD1, GCK, GPC3, HADH, HNF4A, INSR, KDM6A, KMT2D, SLC16A1, CACNA1D, PMM2, TRMT10A and HNF1A genes by targeted next generation sequencing (Agilent custom capture v5.3/Illumina NextSeq500) has been undertaken. Confirmatory dosage analysis of exons 51-54 of the KMT2D genes (NM_003482.3) has been performed by Droplet Digital PCR using EvaGreen.Results: The proband is mosaic for a KMT2D (OMIM 602113) partial gene deletion, of exons 51-54 (g.(49415449)_(49416715)del). His deletion variant is predicted to be pathogenic and the level of mosaicism within his leukocyte DNA is estimated as at least 20%, consistent with a post-zygotic origin. Pathogenic variants in the KMT2D gene cause Kabuki syndrome (4) and hyperinsulinism is a feature of Kabuki syndrome (5).Conclusion & discussion: This result confirms that this patient’s hyperinsulinism is due to a KMT2D gene variant and is suggestive of a diagnosis of Kabuki syndrome. Individuals with Kabuki syndrome have characteristic facial features in addition to a variety of specific congenital anomalies

کلیدواژه ها:

KMT2D gene ، hyperinsulinism ، kabuki syndrome