J Clin Res Pediatr Endocrinol. Ahead of Print: JCRPE-81894 | DOI: 10.4274/jcrpe.galenos.2022.2022-4-14

Endocrine Evaluation and Homeostatic Model Assessment in Patients with Cornelia de Lange Syndrome

Ángela Ascaso¹, Ana Latorre-pellicer¹, Beatriz Puisac¹, Laura Trujillano¹, María Arnedo¹, Ilaria Parenti³, Elena Llorente⁴, Juan José Puente-lanzarote⁴, Ángel Matute-llorente⁵, Ariadna Ayerza-casas⁸, Frank J. Kaiser⁶, Feliciano J. Ramos², Juan Pié¹, Gloria Bueno-lozano^7
1Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and ISS-Aragon, Zaragoza, Spain
²Unit of Clinical Genetics, Department of Paediatrics, Hospital Clínico Universitario "Lozano Blesa", CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain
³Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany
⁴Clinical Biochemistry Service, Hospital Clinico Universitario “Lozano Blesa”, Zaragoza, Spain
⁵GENUD (Growth, Exercise, Nutrition and Development) Research Group. Department of Physiatry and Nursing, Faculty of Health and Sport Science, Huesca, Spain
⁶Essener Zentrum für Seltene Erkrankung (EZSE), Universitätsmedizin Essen, Germany
⁷Unit of Endocrinology, Department of Paediatrics, Hospital Clínico Universitario "Lozano Blesa", CIBERobn-GCV02 and IIS-Aragon, Zaragoza, Spain
⁸Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany and Essener Zentrum für Seltene Erkrankung (EZSE), Universitätsmedizin Essen, Germany

Objective: The aim of this study was to expand knowledge about endocrine disorders in individuals with Cornelia de Lange syndrome (CdLS), a rare developmental genetic disorder with anomalies in multiple organs and systems.
Methods: Hormone levels, clinical scores, anthropometric measurements, and molecular analysis were assessed in 24 individuals with CdLS. Results: Hyperprolactinemia was the most common endocrine disorder. Three patients showed subclinical hypothyroidism. In the gonadotropic axis, mildly delayed puberty was observed, as well as genital anomalies, such as cryptorchidism. Despite short stature, levels of insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 were normal, on average. Three prepubertal individuals without risk factors had higher than normal values for the homeostatic model assessment of insulin resistance (HOMA-IR) and for insulinemia, suggesting insulin resistance. Furthermore, two adults had elevated BMIs associated with HOMA-IR values over the cut-off values.
Conclusion: CdLS can lead to dysregulation of the endocrine system, particularly in patients with high HOMA-IR values and insulinemia who are at risk of insulin resistance. Therefore, clinical follow-ups with hormonal assessments are proposed for individuals with CdLS.

Keywords: Cornelia de Lange syndrome, HOMA-index, insulin resistance, endocrine evaluation and hypothalamic-pituitary axis.

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