Background: Kabuki syndrome (KS) is a rare multiple congenital malformation and intellectual disability syndrome. KS is caused by pathogenic variants in the genes KMT2D or KDM6A. In 0.3-4% of patients, KS is reported to be associated with hyperinsulinemic hypoglycemia. The objective of this study was to characterize the clinical, biochemical and molecular data of children with KS and hyperinsulinemic hypoglycemia.
Methods: Clinical, biochemical and molecular data from 5 children with KS and hyperinsulinemic hypoglycemia from three centres were retrospectively analysed.
Results: 5 female patients were identified with 5 different pathogenic variants in KDM6A (n = 3) and KMT2D (n = 2). All of them presented hyperinsulinemic hypoglycemia at day one of life and showed good response to treatment with diazoxide. The children were diagnosed with KS between the age of 10 months and 9 years. Typical clinical features of KS were seen in all patients but were of great variety, including dysmorphic facial features (n=5), cardiac anomalies (n=4), feeding difficulties with failure to thrive (n=4), and neurological symptoms such as afebrile seizures, muscle hypotonia and developmental delay (n=4).
Conclusion: In our study all children were diagnosed with hyperinsulinemic hypoglycemia in the first days of life, however, it took months to years to diagnose the KS. The predominance of female gender and KDM6A-related KS in our small cohort surprises, however, existing literature does not show similar findings. To facilitate the early identification of KS associated problems and to improve the treatment of affected patients with KS, KS should be considered in children with hyperinsulinemic hypoglycemia especially if there are other extrapancreatic/syndromic features.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology