Congenital hyperinsulinism as the presenting feature of Kabuki syndrome: clinical and molecular characterization of 9 affected individuals.

Genet Med 2019 01 15;21(1):233-242. Epub 2018 Jun 15.

Department of Human Genetics, University of Chicago Genetic Services Laboratory, The University of Chicago, Chicago, Illinois, USA.

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 9 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 = 4). 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.

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http://dx.doi.org/10.1038/s41436-018-0013-9DOI Listing
January 2019
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