HutchinsonGilford

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder characterized by accelerated aging that begins in early childhood. The condition is named after physicians Jonathan Hutchinson and Hastings Gilford, who described its features in the late 19th century, and the term progeria comes from Greek for “before aging.”

Most cases arise from de novo mutations in the LMNA gene, which encodes lamins A and C. The common LMNA mutation creates progerin, a faulty form of lamin A that disrupts the nuclear envelope and cellular structure. Inheritance is autosomal dominant, but familial recurrence is rare because most cases occur anew.

Clinical features typically appear in the first year or two of life. Children with HGPS usually show growth delay, loss of body fat and muscle, and characteristic facial features such as a thin nose and small jaw. Hair loss, aged-appearing skin, joint stiffness, and skeletal changes are common. Cardiovascular disease, including progressive atherosclerosis, is a major cause of morbidity and early death.

Diagnosis is based on clinical presentation and can be confirmed by genetic testing for LMNA mutations. There is currently no cure. Management is supportive and multidisciplinary, focusing on maintaining growth, nutrition, mobility, and cardiovascular health. In 2020, lonafarnib, a farnesyltransferase inhibitor, was approved as a disease-modifying therapy and has been associated with improvements in longevity and weight in some patients.

Epidemiologically, HGPS is extremely rare, affecting an estimated few individuals per 10 million births, with roughly several hundred cases documented worldwide. Research continues into additional treatments and potential genetic approaches.