Clinical Presentation and Molecular Characteristics of Kabuki Syndrome With Congenital Hyperinsulinism: A Retrospective Study.

INTRODUCTION

Kabuki syndrome (KS) is a rare disease predisposing to congenital hyperinsulinism (CHI). The incidence of CHI in KS may be higher than considered in practice, and appropriate management of hypoglycemia would reduce long-term neurologic morbidity in these patients. Thus, the aims of our study were to estimate the occurrence rate of CHI-related hypoglycaemia in KS, to describe its evolution, and to identify potential genotype-phenotype correlations.

METHODS

We conducted a single-centre retrospective study in patients with KS from 1999 to 2024.

RESULTS

Among the 18 patients identified with KS included in the study, six (33%) presented neonatal hypoglycaemia, of whom five (28%) demonstrated CHI. Of these five, three had persistent CHI. Only the three patients with this condition required anti-hypoglycaemic drugs. They all responded well to diazoxide monotherapy, and one then needed the addition of octreotide. Genetically, all patients had heterozygous variants of the KMT2D gene except one, who had a heterozygous microdeletion of the same gene. Among these 17 variants, the majority were truncating variants (10/17, 59%) (three nonsense variants, six frameshift variants, and one splicing variant). Seven variants were missense variants (7/17, 41%). Among the six patients with hypoglycaemia, all had nonsense or frameshift variants in the C-terminal part of the KMT2D protein.

CONCLUSIONS

This study illustrates the importance of systematic screening for hypoglycaemia in patients with early diagnosis of KS. Conversely, newborns or infants with CHI should be considered and possibly tested for this etiological diagnosis.