Quantification of Lateralized Overgrowth and Genotype-Driven Tissue Composition

Abstract

Lateralized overgrowth (LO) is characterized by excessive growth of one side of the body compared to the other. LO can present as isolated (ILO) or within syndromes, like Beckwith-Wiedemann Spectrum (BWSp) and PIK3CA-related overgrowth spectrum (PROS). Currently, the diagnosis of LO relies on clinical evaluation and lacks a standardized method. In this study, we evaluated total body dual-energy X-ray absorptiometry (TB-DXA) as a potential tool for standardizing LO assessment. Patients with LO underwent both clinical evaluation and TB-DXA. TB-DXA data, including total mass, mass of the three main tissue components (adipose, muscle, and bone), total mass discrepancy ratio, relative tissue composition, and discrepancy of relative tissue composition were calculated and compared with clinical findings. Differences between affected regions and the contralateral side were assessed. A total of 46 patients (61% PROS, 24% BWSp, 15% ILO) were included in this study. TB-DXA detected overgrowth regions aligned with clinical evaluation in 91% of cases and was able to identify localized overgrowth even when clinically overlooked. Additionally, TB-DXA revealed differences in tissue composition between affected and unaffected regions for symmetrical body areas, with these differences varying by diagnostic subgroup. Different patterns of tissue composition overgrowth were observed among different conditions, with PROS predominantly showing adipose tissue overgrowth, while BWSp/ILO mainly osteo-muscular overgrowth. TB-DXA is an accurate, safe, and reproducible tool in the clinical setting providing an objective method for identifying and quantifying LO. It offers valuable guidance for clinicians in the diagnosis and management of LO.