Hutchinson-Gilford Progeria Syndrome: a Comprehensive Review

Abstract

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder causing accelerated aging in children, with an incidence of approximately 1 in 20 million live births. First described by Jonathan Hutchinson and Hastings Gilford in the late 19th century, HGPS is caused by a mutation in the LMNA gene, leading to the production of a defective protein called progerin. Progerin disrupts the nuclear envelope's integrity, resulting in cellular abnormalities and premature aging. Clinically, HGPS is characterized by distinctive facial features, growth retardation, skin changes, joint contractures, and cardiovascular complications, primarily arteriosclerosis, which often lead to early death due to myocardial infarction or stroke. Diagnosis is primarily clinical, supported by genetic testing to confirm the LMNA mutation. Management focuses on symptomatic relief and improving quality of life, with cardiovascular monitoring being crucial. Farnesyltransferase inhibitors (FTIs) have shown potential in reducing progerin levels and improving cellular function. Supportive therapies, including physical and occupational therapy, are essential for managing the disease. Future research aims to develop effective treatments, with gene editing technologies like CRISPR/Cas9 showing promise in correcting the LMNA mutation. Understanding HGPS can provide insights into the natural aging process and inform novel anti-aging therapies. Collaborative efforts are vital for advancing research and improving patient outcomes.