STAG1 Disease, Central Precocious Puberty, and Bone Fragility—A Case Report

TL;DR

A case report describes a girl with a STAG1 gene variant, intellectual disability, early puberty, and bone fragility, highlighting the complex and poorly understood nature of cohesinopathies.

Contribution

This case adds to the understanding of STAG1-related cohesinopathies by highlighting unusual features like central precocious puberty and bone fragility.

Findings

The patient had a pathogenic STAG1 variant and features like intellectual disability and early puberty.

Current molecular tools struggle to fully explain overlapping and seemingly unrelated clinical features in cohesinopathy cases.

The case suggests the need for further investigation into the clinical spectrum of STAG1-related disorders.

Abstract

Background: Previously reported STAG1 gene-related cohesinopathies describe a range of clinical features, typically including intellectual disability (ID), facial dysmorphisms, and limb anomalies. Case presentation: We present the case of an 8-year-old girl with main findings including ID, central precocious puberty (CPP), and bone fragility. Panel genetic testing revealed a pathogenic STAG1 variant, NM_005862.3:c.2116del p.(Asp706Ilefs*15), which can only partially explain the clinical phenotype. Reports of STAG1-related cohesinopathies, including ours, have consistently described developmental and intellectual disabilities. In our case, the etiology of CPP and bone fragility remains unexplained. We discuss the challenges and limitations of current molecular tools in assessing cases with overlapping, apparently unlinked phenotypes, while speculating whether the common occurrence could be explained by STAG1 instead. Conclusions: The clinical spectrum of cohesinopathies is still poorly understood. Complex phenotypes with apparently unrelated clinical features warrant further careful investigation and illustrate the challenges of molecular diagnosis.

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