Clinical Characteristics of Patients With Kabuki Syndrome at a Single Tertiary Children's Hospital

ABSTRACT Kabuki syndrome (KS) is a multisystem disorder characterized by facial dysmorphic features, growth delays, skeletal anomalies, and variable intellectual disability (ID) due to pathogenic variants in KMT2D and KDM6A . Significant phenotypic variability has been reported in patients with KS. To further characterize the variability observed in the genomic sequencing era, comprehensive genotypic and phenotypic information from 36 patients with KS and likely pathogenic or pathogenic KMT2D or KDM6A variants at the Children's Hospital of Philadelphia (CHOP) was collected. Dysmorphic features, growth restriction, and developmental delays were commonly reported, as expected. Hyperinsulinism (HI) was seen more frequently than in previously published cohorts. Patients diagnosed with HI were more likely to require neonatal intensive care unit admission and feeding tube(s). Intellectual disability was variable in severity and less frequent than previously reported. This study highlights the wide phenotypic spectrum of KS and expands our knowledge of the diagnostic process for KS. This study is limited by potential ascertainment bias as CHOP is a HI Center of Excellence, however, our cohort is unique as many were ascertained with disease‐agnostic testing. Screening for hyperinsulinism, including consideration of diagnostic fast, at time of KS diagnosis is warranted to prevent long‐term neurologic effects of untreated hypoglycemia.