Congenital hyperinsulinism as the presenting feature of Kabuki syndrome: clinical and molecular characterization of 10 affected individuals

Kai Lee Yap, Amy E.Knight Johnson, David Fischer, Priscilla Kandikatla, Jacea Deml, Viswateja Nelakuditi, Sara Halbach, George S. Jeha, Lindsay C. Burrage, Olaf Bodamer, Valeria C. Benavides, Andrea M. Lewis, Sian Ellard, Pratik Shah, Declan Cody, Alejandro Diaz, Aishwarya Devarajan, Lisa Truong, Siri Atma W. Greeley, Diva D. de Leó-CrutchlowAndrew C. Edmondson, Soma Das, Paul Thornton, Darrel Waggoner, Daniela Del Gaudio

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Purpose: Describe the clinical and molecular findings of patients with Kabuki syndrome (KS) who present with hypoglycemia due to congenital hyperinsulinism (HI), and assess the incidence of KS in patients with HI. Methods: We documented the clinical features and molecular diagnoses of 10 infants with persistent HI and KS via a combination of sequencing and copy-number profiling methodologies. Subsequently, we retrospectively evaluated 100 infants with HI lacking a genetic diagnosis, for causative variants in KS genes. Results: Molecular diagnoses of KS were established by identification of pathogenic variants in KMT2D (n = 5) and KDM6A (n = 5). Among the 100 infants with HI of unknown genetic etiology, a KS diagnosis was uncovered in one patient. Conclusions: The incidence of HI among patients with KS may be higher than previously reported, and KS may account for as much as 1% of patients diagnosed with HI. As the recognition of dysmorphic features associated with KS is challenging in the neonatal period, we propose KS should be considered in the differential diagnosis of HI. Since HI in patients with KS is well managed medically, a timely recognition of hyperinsulinemic episodes will improve outcomes, and prevent aggravation of the preexisting mild to moderate intellectual disability in KS.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
JournalGenetics in Medicine
Issue number1
StatePublished - Jan 1 2019


  • Hypoglycemia
  • KDM6A
  • KMT2D
  • Kabuki syndrome
  • hyperinsulinism

ASJC Scopus subject areas

  • Genetics(clinical)

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