Pathophysiology of Hutchinson Gilford Progeria Syndrome: Current Knowledge and Future Directions

Abstract

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder characterized by accelerated aging in children. It was first described by Jonathan Hutchinson in 1886 and later independently by Hastings Gilford in 1897. Children with HGPS typically exhibit growth retardation, loss of body fat and hair, skin changes, joint stiffness, and severe cardiovascular complications. The disorder is caused by a mutation in the LMNA gene, which encodes lamin A, a protein essential for maintaining the structural integrity of the cell nucleus. This mutation leads to the production of an abnormal form of lamin A, called progerin, which disrupts nuclear architecture and cellular function, resulting in the premature aging phenotype observed in HGPS.

Methods: We conducted a comprehensive search from April to June 2024 using PubMed and Google Scholar. Keywords used ("Hutchinson-Gilford Progeria Syndrome" OR Progeria) AND (pathophysiology OR "genetic disorders" OR "LMNA gene mutation" OR "Lamin A protein" OR "nuclear envelope" OR "cardiovascular complications" OR "clinical features" OR "molecular mechanisms" OR "therapeutic approaches"). The review included peer-reviewed original research papers, systematic reviews, and meta-analyses.

Conclusion: HGPS is characterized by premature aging due to a mutation in the LMNA gene. Despite progress in understanding its molecular mechanisms and improving clinical management, significant obstacles remain due to the rarity of the condition and ethical considerations in research and treatment. Future research should aim to advance therapeutic strategies through innovative approaches.