Phenotype and Course of Hutchinson–Gilford Progeria Syndrome

• Published in: The New England journal of medicine Vol. 358; no. 6; pp. 592 - 604
• Main Authors: Merideth, Melissa A, Gordon, Leslie B, Clauss, Sarah, Sachdev, Vandana, Smith, Ann C.M, Perry, Monique B, Brewer, Carmen C, Zalewski, Christopher, Kim, H. Jeffrey, Solomon, Beth, Brooks, Brian P, Gerber, Lynn H, Turner, Maria L, Domingo, Demetrio L, Hart, Thomas C, Graf, Jennifer, Reynolds, James C, Gropman, Andrea, Yanovski, Jack A, Gerhard-Herman, Marie, Collins, M.D. Francis S, Nabel, Elizabeth G, Cannon, Richard O, Gahl, William A, Introne, Wendy J
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 07.02.2008
• Subjects: Adolescent; Biological and medical sciences; Blood Chemical Analysis; Child; Child, Preschool; Children & youth; Disease Progression; Female; General aspects; Genetic disorders; Genotype & phenotype; Growth; Humans; Infant; Male; Medical sciences; Pediatrics; Phenotype; Progeria - blood; Progeria - pathology; Progeria - physiopathology; Dwarfism; Medicine; Skin disease; Phenotype; Progeria; Syndrome
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa0706898

This article describes the detailed phenotype of 15 children, 1 to 17 years of age, with Hutchinson–Gilford progeria syndrome, a rare, sporadic autosomal dominant premature aging syndrome causing death at approximately 13 years of age. Most cases are caused by an LMNA gene mutation that produces an abnormal lamin A, “progerin.” Since progerin accumulates in normal cells with age, understanding this syndrome may offer insight into normal aging. This article describes the detailed phenotype of 15 children with Hutchinson–Gilford progeria syndrome, a rare, sporadic autosomal dominant premature aging syndrome causing death at approximately 13 years of age. Some aspects of human aging appear to be dramatically accelerated in the Hutchinson–Gilford progeria syndrome, an extremely rare sporadic disorder (Figure 1). 1 – 3 Within approximately 13 years after birth, affected children die from cardiovascular disease. The cause is abnormal lamin A (denoted “progerin,” to distinguish it from normal lamin A), which is produced by an activated cryptic splice donor site created by a change from glycine GGC to glycine GGT in codon 608 of exon 11 of the lamin A ( LMNA ) gene. 4 , 5 Progerin disrupts the structural integrity of the inner nuclear membrane in a dominant negative fashion. . . .