Dataset Information

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

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.

SUBMITTER: Yap KL

PROVIDER: S-EPMC7597849 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Yap Kai Lee KL Johnson Amy E Knight AEK Fischer David D Kandikatla Priscilla P Deml Jacea J Nelakuditi Viswateja V Halbach Sara S Jeha George S GS Burrage Lindsay C LC Bodamer Olaf O Benavides Valeria C VC Lewis Andrea M AM Ellard Sian S Shah Pratik P Cody Declan D Diaz Alejandro A Devarajan Aishwarya A Truong Lisa L Greeley Siri Atma W SAW De Leó-Crutchlow Diva D DD Edmondson Andrew C AC Das Soma S Thornton Paul P Waggoner Darrel D Del Gaudio Daniela D

Genetics in medicine : official journal of the American College of Medical Genetics 20180615 1

<h4>Purpose</h4>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.<h4>Methods</h4>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, ...[more]

PMID: 29907798

Similar Datasets

Project description:Kabuki syndrome (KS) is a Mendelian Disorder of the Epigenetic Machinery (MDEM) caused by loss of function variants in either of two genes involved in the regulation of histone methylation, KMT2D (34-76%) or KDM6A (9-13%). Previously, representative neurobehavioral deficits of KS were recapitulated in a mouse model, emphasizing the role of KMT2D in brain development, specifically in ongoing hippocampal neurogenesis in the granule cell layer of the dentate gyrus. Interestingly, anxiety, a phenotype that has a known association with decreased hippocampal neurogenesis, has been anecdotally reported in individuals with KS. In this study, anxiety and behavior were assessed in a cohort of 60 individuals with molecularly confirmed KS and 25 unaffected biological siblings, via questionnaires (SCARED/GAS-ID and CBCL/ABCL). Participant age ranged from 4 to 43 years old, with 88.3% of participants having a pathogenic variant in KMT2D, and the rest having variants in KDM6A. In addition, data was collected on adaptive function and positive affect/quality of life in participants with KS using appropriate online surveys including ABAS-III and PROMIS Positive Affect. Survey scores were compared within the KS participants across age groups and between KS participants and their unaffected siblings. We found that children with KS have significantly higher anxiety scores and total behavior problem scores than their unaffected siblings (p = 0.0225, p < 0.0001). Moreover, a large proportion of affected individuals (22.2% of children and 60.0% of adults) surpassed the established threshold for anxiety; this may even be an underestimate given many patients are already treated for anxiety. In this sample, anxiety levels did not correlate with level of cognitive or adaptive function in any KS participants, but negatively correlated with positive affect in children with KS (p = 0.0005). These findings indicate that anxiety is a common neurobehavioral feature of KS. Providers should therefore carefully screen individuals with KS for anxiety as well as other behavioral issues in order to allow for prompt intervention. Neurobehavioral anxiety measures may also prove to be important outcome measures for clinical trials in KS.

Dataset Information

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

Purpose

Methods

Results

Conclusions

Publications

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

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