Progeria (Hutchinson-Gilford Syndrome): Equal Gender Incidence

Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare (<1 in 20 million) autosomal dominant condition caused by a de novo point mutation in LMNA (c.1824C>T, p.Gly608Gly) → toxic progerin protein.

Gender Distribution

Equal male:female ratio (1:1). No sex predilection; mutation arises sporadically in paternal sperm (advanced paternal age association).

Key Features

• Onset: 12–24 months (failure to thrive, scleroderma-like skin, alopecia, lipodystrophy)
• Characteristic facies: micrognathia, beaked nose, prominent eyes/veins
• Accelerated atherosclerosis → MI/stroke (mean death age 14.5 yrs, range 6–20)
• Intelligence normal

Treatment

• Lonafarnib (farnesyltransferase inhibitor): FDA-approved 2020; extends median survival ~2.5 years.
• Supportive: aspirin, statins, PT/OT, dental, nutritional optimization.
• Clinical trials: gene editing, progerin antisense oligonucleotides.