title: Phenotype and course of Hutchinson-Gilford progeria syndrome.
abstract: 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.)
authors.affiliation: National Human Genome Research Institute, Intramural Office of Rare Disease, National Institutes of Health, Bethesda, MD 20892-1851, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Merideth
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Gordon
authors.forename: Sarah
authors.initials: S
authors.lastname: Clauss
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.forename: Ann C M
authors.initials: AC
authors.lastname: Smith
authors.forename: Monique B
authors.initials: MB
authors.lastname: Perry
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Brewer
authors.forename: Christopher
authors.initials: C
authors.lastname: Zalewski
authors.forename: H Jeffrey
authors.initials: HJ
authors.lastname: Kim
authors.forename: Beth
authors.initials: B
authors.lastname: Solomon
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
authors.forename: Lynn H
authors.initials: LH
authors.lastname: Gerber
authors.forename: Maria L
authors.initials: ML
authors.lastname: Turner
authors.forename: Demetrio L
authors.initials: DL
authors.lastname: Domingo
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Hart
authors.forename: Jennifer
authors.initials: J
authors.lastname: Graf
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Andrea
authors.initials: A
authors.lastname: Gropman
authors.forename: Jack A
authors.initials: JA
authors.lastname: Yanovski
authors.forename: Marie
authors.initials: M
authors.lastname: Gerhard-Herman
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Nabel
authors.forename: Richard O
authors.initials: RO
authors.lastname: Cannon
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Introne
mesh_terms: D000293:Adolescent; D001774:Blood Chemical Analysis; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006128:Growth; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D011371:Progeria / Q000097:blood / Q000473:pathology / Q000503:physiopathology*