Intrafamilial phenotypic heterogeneity in siblings with pseudohypoparathyroidism 1B due to maternal STX16 deletion

John Odom; Carlos A. Bacino; Lefkothea P. Karaviti; Weimin Bi; Alfonso Hoyos-Martinez

doi:10.1515/jpem-2023-0249

Article

Intrafamilial phenotypic heterogeneity in siblings with pseudohypoparathyroidism 1B due to maternal STX16 deletion

John Odom , Carlos A. Bacino , Lefkothea P. Karaviti , Weimin Bi and Alfonso Hoyos-Martinez

Published/Copyright: December 14, 2023

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 1

Abstract

Objectives

Pseudohypoparathyroidism (PHP1B) is most commonly caused by epigenetic defects resulting in loss of methylation at the GNAS locus, although deletions of STX16 leading to GNAS methylation abnormalities have been previously reported. The phenotype of this disorder is variable and can include hormonal resistances and severe infantile obesity with hyperphagia. A possible time relationship between the onset of obesity and endocrinopathies has been previously reported but remains unclear. Understanding of the condition’s natural history is limited, partly due to a scarcity of literature, especially in children.

Case presentation

We report three siblings with autosomal dominant PHP1B caused by a deletion in STX16 who presented with early childhood onset PTH-resistance with normocalcemia with a progressive nature, accompanied by TSH-resistance and severe infantile obesity with hyperphagia in some, not all of the affected individuals.

Conclusions

PHP1B from a STX16 deletion displays intrafamilial phenotypic variation. It is a novel cause of severe infantile obesity, which is not typically included in commercially available gene panels but must be considered in the genetic work-up. Finally, it does not seem to have a clear time relationship between the onset of obesity and hormonal resistance.

Keywords: pseudohypoparathyroidism type 1B; STX16 ; infantile obesity; GNAS

Corresponding author: Alfonso Hoyos-Martinez, Department of Pediatrics, Division of Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA; and 6701 Fannin Street, Suite 1020, Houston, TX 77030, USA, E-mail: alfonso.hoyosmartinez@bcm.edu

Research ethics: The local Institutional Review Board approved the study (H-47418).
Informed consent: Informed consent was obtained from the parent of the siblings.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Research funding: None declared.

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Received: 2023-05-31

Accepted: 2023-11-15

Published Online: 2023-12-14

Published in Print: 2024-01-29

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0249

Keywords for this article

pseudohypoparathyroidism type 1B; STX16; infantile obesity; GNAS