Hutchinson-Gilford progeria syndrome.
Level 5 - mechanism / opinion, no new human data
Narrative review chapter summarizing clinical features, autopsy data, and preclinical models.
PubMed 26564085 · doi:10.1016/B978-0-444-62702-5.00018-4
What was done
This narrative review chapter synthesizes clinical, pathological, and preclinical data on Hutchinson-Gilford progeria syndrome (HGPS), with a specific focus on genetics, pathobiology, management, and cutaneous and neurological manifestations.
What was found
HGPS causes fatal cardiovascular disease and strokes, with an average age at death of 14.6 years. Cerebrovascular disease features carotid or vertebral artery stenosis, occlusion, calcification, prominent collateral vessels, and frequent clinically silent strokes involving both large and small vessels. Despite widespread segmental aging, patients lack apparent cognitive deterioration. Limited human autopsy records demonstrate an absence of dementia-related neuropathology or Alzheimer-type changes. Transgenic mice expressing the common HGPS mutation exhibited ultrastructural nuclear distortions in neurons (irregular shapes and severe invaginations) without abnormal tau, inclusions, or significant alterations in hippocampal gene expression.
Why it matters
The review synthesizes clinical and experimental evidence showing that while HGPS causes profound cerebrovascular pathology, neural parenchyma and cognitive function remain relatively preserved.
Limits
As a narrative review, it lacks systematic search criteria, meta-analytic data, and quality assessments. Findings are constrained by the extreme rarity of HGPS and the very small number of available human autopsy specimens.
Cited by
- supports Children born with progeria typically do not live past their teens and suffer from accelerated aging, cardiomyopathy, and stroke.