What is Hutchinson-Gilford Progeria Syndrome (HGPS)?

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Last updated: April 23, 2025 • View editorial policy

From the Guidelines

Progeria patients should be treated with lonafarnib (Zokinvy) to help extend lifespan by reducing the buildup of defective progerin, as it has been shown to be effective in managing symptoms and complications of the disease. Progeria is a rare genetic disorder characterized by accelerated aging in children, caused by a mutation in the LMNA gene, which produces an abnormal form of the protein lamin A called progerin 1. This protein accumulates in cells, causing them to become unstable and leading to premature aging. Children with progeria typically appear normal at birth but begin showing symptoms within the first two years of life, including growth failure, loss of body fat, hair loss, aged-looking skin, stiffness of joints, and cardiovascular disease. Most children with progeria die from heart attacks or strokes at an average age of 14-15 years.

Some key aspects of progeria management include:

  • Low-dose aspirin to reduce the risk of heart attacks and strokes
  • Physical and occupational therapy to help with joint stiffness
  • Nutritional support to maintain adequate caloric intake
  • Regular cardiovascular monitoring is essential for these patients Research continues to explore potential treatments including gene therapy approaches that might correct the underlying genetic defect, such as the use of DNA methylation aging clocks to monitor disease progression and response to treatment 1. However, current evidence suggests that lonafarnib (Zokinvy) is the most effective treatment available for extending lifespan and improving quality of life for progeria patients.

The use of DNA methylation aging clocks, such as the "Skin-Blood" clock, has been shown to be useful in monitoring age acceleration in progeroid disorders, including Hutchinson-Gilford progeria syndrome 1. These clocks can provide valuable information on the biological age of progeria patients and help guide treatment decisions. However, the primary focus of treatment should be on reducing the buildup of defective progerin and managing symptoms and complications, rather than solely relying on epigenetic clocks.

From the Research

Definition and Causes of Progeria

  • Progeria, also known as Hutchinson-Gilford Progeria Syndrome (HGPS), is an extremely rare and fatal genetic disorder that causes premature aging in children 2.
  • It is caused by a mutation in the LMNA gene, which yields the farnesylated aberrant protein progerin 2, 3.

Symptoms and Effects of Progeria

  • Progeria leads to accelerated atherosclerosis, resulting in death at an average age of 14.6 years 2.
  • It affects the musculoskeletal system, causing skeletal dysplasia and degenerative joint diseases 4.
  • The disease also affects the cardiovascular system, leading to severe perimorbid cardiovascular disease 3.

Treatment Options for Progeria

  • Lonafarnib, a farnesyltransferase inhibitor, has been shown to improve cardiovascular function and survival in patients with HGPS 3, 5, 6.
  • Combination therapy with lonafarnib, pravastatin, and zoledronic acid has been evaluated, with improvements in bone mineral density and musculoskeletal phenotype 2, 4.
  • The US Food and Drug Administration has approved lonafarnib (Zokinvy) for the treatment of HGPS and processing-deficient progeroid laminopathies 5, 6.

Clinical Trials and Research

  • Clinical trials have demonstrated the efficacy of lonafarnib in improving survival and cardiovascular function in patients with HGPS 2, 3, 6.
  • Preclinical trials have also shown promising results, with improvements in bone structure and mechanical properties, as well as cartilage structural parameters 4.
  • Further research is needed to fully understand the effects of lonafarnib and other treatment options on progeria and its related diseases 3, 4, 5, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.