BACKGROUND: Hutchinson-Gilford progeria syndrome is a rare, sporadic, autosomal 
dominant syndrome that involves premature aging, generally leading to death at 
approximately 13 years of age due to myocardial infarction or stroke. The 
genetic basis of most cases of this syndrome is a change from glycine GGC to 
glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic 
splice donor site to produce abnormal lamin A; this disrupts the nuclear 
membrane and alters transcription.
METHODS: We enrolled 15 children between 1 and 17 years of age, representing 
nearly half of the world's known patients with Hutchinson-Gilford progeria 
syndrome, in a comprehensive clinical protocol between February 2005 and May 
2006.
RESULTS: Clinical investigations confirmed sclerotic skin, joint contractures, 
bone abnormalities, alopecia, and growth impairment in all 15 patients; 
cardiovascular and central nervous system sequelae were also documented. 
Previously unrecognized findings included prolonged prothrombin times, elevated 
platelet counts and serum phosphorus levels, measured reductions in joint range 
of motion, low-frequency conductive hearing loss, and functional oral deficits. 
Growth impairment was not related to inadequate nutrition, insulin 
unresponsiveness, or growth hormone deficiency. Growth hormone treatment in a 
few patients increased height growth by 10% and weight growth by 50%. 
Cardiovascular studies revealed diminishing vascular function with age, 
including elevated blood pressure, reduced vascular compliance, decreased 
ankle-brachial indexes, and adventitial thickening.
CONCLUSIONS: Establishing the detailed phenotype of Hutchinson-Gilford progeria 
syndrome is important because advances in understanding this syndrome may offer 
insight into normal aging. Abnormal lamin A (progerin) appears to accumulate 
with aging in normal cells. (ClinicalTrials.gov number, NCT00094393.)