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Genet Med. 2019 Jan;21(1):233-242. doi: 10.1038/s41436-018-0013-9. Epub 2018 Jun 15.

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

Author information

1
Department of Human Genetics, University of Chicago Genetic Services Laboratory, The University of Chicago, Chicago, Illinois, USA.
2
Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
3
Pediatric Diabetes and Endocrinology, Texas Children's Hospital, Houston, Texas, USA.
4
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
5
Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
6
Division of Pediatric Endocrinology, University of Illinois College of Medicine, Peoria, Illinois, USA.
7
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Newcastle upon Tyne, UK.
8
Great Ormond Street Hospital, London, UK.
9
Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
10
Pediatric Endocrinology, Pediatric Specialists of America, Nicklaus Children's Hospital, Miami, Florida, USA.
11
Cook Children's Medical Center, Fort Worth, Texas, USA.
12
Department of Pediatrics and Medicine, The University of Chicago Medicine, Chicago, Illinois, USA.
13
Department of Pediatrics, Divisions of Endocrinology and Genetics, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
14
Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
15
Department of Human Genetics, University of Chicago Genetic Services Laboratory, The University of Chicago, Chicago, Illinois, USA. ddelgaudio@bsd.uchicago.edu.

Abstract

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.

KEYWORDS:

Hypoglycemia; KDM6A; KMT2D; Kabuki syndrome; hyperinsulinism

PMID:
29907798
DOI:
10.1038/s41436-018-0013-9
[Indexed for MEDLINE]

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