Lateralized and Segmental Overgrowth in Children.

Area of Science:

• Genetics
• Developmental Biology
• Pediatric Medicine

Background:

• Congenital lateralized or segmental overgrowth (LO) disorders are characterized by heterogeneous conditions with increased tissue growth in specific body regions.
• These conditions can range from mild asymmetry to severe, progressive overgrowth with significant complications, affecting various embryonic tissues.
• LO disorders often present overlapping phenotypes, complicating accurate diagnosis and management.

Purpose of the Study:

• To review the classification of congenital lateralized or segmental overgrowth disorders based on molecular defects and cellular signaling pathways.
• To highlight the diagnostic challenges posed by overlapping phenotypes in LO disorders.
• To emphasize the importance of precise diagnosis for tailored management, including cancer surveillance and potential therapeutic strategies.

Main Methods:

• Review of recent literature on congenital lateralized or segmental overgrowth disorders.
• Analysis of next-generation sequencing findings to understand molecular underpinnings.
• Categorization of LO disorders based on affected cellular signaling pathways.

Main Results:

• LO disorders are increasingly classified into distinct groups such as Beckwith-Wiedemann spectrum (BWSp), PIK3CA/AKT-related overgrowth spectrum (PROS/AROS), mosaic RASopathies, PTEN Hamartoma Tumor Syndrome, and isolated LO (ILO).
• Molecular defects are often somatic genetic or epigenetic anomalies affecting cell proliferation.
• Some LO disorders share molecular mechanisms with cancer, indicating potential therapeutic targets.

Conclusions:

• Accurate classification of LO disorders based on molecular pathways is crucial for effective management and surveillance.
• Early identification of cancer risk in certain LO disorders necessitates childhood tumor screening.
• Understanding shared molecular mechanisms with cancer opens new therapeutic avenues for severe LO cases.