Progeria

Progeria (Hutchinson-Gilford progeria syndrome, HGPS) is an extraordinarily rare autosomal dominant disorder caused by a point mutation (c.1824C>T) in the LMNA gene occurring de novo in almost all cases. The mutation produces a truncated lamin A protein that accumulates within the nuclear envelope, impairing nuclear function and causing cellular dysfunction. Affected children appear normal at birth but within the first year develop signs of rapidly accelerated aging: growth failure despite normal appetite, progressive alopecia with characteristic loss of eyebrows and lashes, distinctive facial features (micrognathia, prominent ears), and development of cardiovascular disease. Progressive atherosclerosis leads to myocardial infarction and stroke, typically in early teens. Children develop age-related diseases including hypertension, stiff joints, and skeletal abnormalities. Median lifespan is approximately 13-14 years, with death usually from cardiac events. The rapidity of aging makes progeria invaluable for studying aging biology.