Congenital Hyperinsulinism in Infants with Turner Syndrome: Possible Association with Monosomy X and KDM6A Haploinsufficiency

Overview

Journal Horm Res Paediatr

Publisher Karger

Specialties Endocrinology
Pediatrics

Date 2018 Jun 15

PMID 29902804

Citations 14

Authors

Christopher E Gibson

Kara E Boodhansingh

Changhong Li

Laura Conlin

Pan Chen

Susan A Becker

Tricia Bhatti

Vaneeta Bamba

N Scott Adzick

Diva D De Leon

Arupa Ganguly

Charles A Stanley

Affiliations

Soon will be listed here.

Abstract

Background: Previous case reports have suggested a possible association of congenital hyperinsulinism with Turner syndrome.

Objective: We examined the clinical and molecular features in girls with both congenital hyperinsulinism and Turner syndrome seen at The Children's Hospital of Philadelphia (CHOP) between 1974 and 2017.

Methods: Records of girls with hyperinsulinism and Turner syndrome were reviewed. Insulin secretion was studied in pancreatic islets and in mouse islets treated with an inhibitor of KDM6A, an X chromosome gene associated with hyperinsulinism in Kabuki syndrome.

Results: Hyperinsulinism was diagnosed in 12 girls with Turner syndrome. Six were diazoxide-unresponsive; 3 had pancreatectomies. The incidence of Turner syndrome among CHOP patients with hyperinsulinism (10 of 1,050 from 1997 to 2017) was 48 times more frequent than expected. The only consistent chromosomal anomaly in these girls was the presence of a 45,X cell line. Studies of isolated islets from 1 case showed abnormal elevated cytosolic calcium and heightened sensitivity to amino acid-stimulated insulin release; similar alterations were demonstrated in mouse islets treated with a KDM6A inhibitor.

Conclusion: These results demonstrate a higher than expected frequency of Turner syndrome among children with hyperinsulinism. Our data suggest that haploinsufficiency for KDM6A due to mosaic X chromosome monosomy may be responsible for hyperinsulinism in Turner syndrome.

Citing Articles

Large copy number variants are an important cause of congenital hyperinsulinism that should be screened for during routine testing.

Flanagan S, Lazaridi I, Mannisto J, Bennett J, Kalyon O, Johnson M Front Endocrinol (Lausanne). 2025; 16:1514916.

PMID: 40041288 PMC: 11876054. DOI: 10.3389/fendo.2025.1514916.

The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development.

Suntharalingham J, Del Valle I, Buonocore F, McGlacken-Byrne S, Brooks T, Ogunbiyi O Commun Biol. 2025; 8(1):249.

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Case Report: The importance of genetic counseling for families with hyperinsulinism.

Sanders V, Lord K, Sigal W, McKnight H, Scott Adzick N, States L Front Pediatr. 2025; 12:1520871.

PMID: 39895985 PMC: 11782026. DOI: 10.3389/fped.2024.1520871.

Clinical and Molecular Characterization of Hyperinsulinism in Kabuki Syndrome.

Rosenfeld E, Mitteer L, Boodhansingh K, Sanders V, McKnight H, De Leon D J Endocr Soc. 2024; 8(7):bvae101.

PMID: 38859884 PMC: 11163021. DOI: 10.1210/jendso/bvae101.

Clinical practice guidelines for the care of girls and women with Turner syndrome.

Gravholt C, Andersen N, Christin-Maitre S, Davis S, Duijnhouwer A, Gawlik A Eur J Endocrinol. 2024; 190(6):G53-G151.

PMID: 38748847 PMC: 11759048. DOI: 10.1093/ejendo/lvae050.

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