Definition of Progeria

Progeria: A rare genetic disorder that causes children to age prematurely. The classic type of childhood progeria is Hutchinson-Gilford syndrome, which is commonly referred to as progeria. It is characterized by dwarfism, baldness, pinched nose, small face and small jaw relative to the head size, delayed tooth formation, aged-looking skin, diminution of fat beneath the skin, stiff joints, and premature arteriosclerosis. Children with the progeria syndrome usually appear normal at birth. However, within a year, their growth rate slows and their appearance begins to change and age prematurely. They often suffer from symptoms typically seen in elderly people, especially severe cardiovascular disease. Death occurs on average at age 13, usually from heart attack or stroke.

Progeria is due to a single-letter "misspelling" in a gene on chromosome 1 that codes for lamin A, a protein that is a key component of the membrane surrounding the cell's nucleus. Most children with classic progeria harbor exactly the same misspelling in the lamin A (LMNA) gene, a substitution of just a single DNA base -- a change from cytosine (C) to thymine (T) -- among the gene's 25,000 base pairs. In a few progeria patients there may be a different single base substitution such as guanine (G) to adenine (A) just two bases upstream. In every instance, the parents are normal indicating that the misspelling is a new, or "de novo," mutation in the child. The minute change in the LMNA gene changes the way in which the sequence is spliced by the cell's protein-making machinery. The end result is the production of an abnormal lamin A protein that is missing a stretch of 50 amino acids near one of its ends.

Different mutations in other regions of the LMNA gene are responsible for a half-dozen other rare, genetic disorders. Those disorders are: Emery-Dreifuss muscular dystrophy type 2, limb girdle muscular dystrophy type 1B, Charcot-Marie-Tooth disorder type 2B1, the Dunnigan type of familial partial lipodystrophy, mandibuloacral dysplasia and a familial form of dilated cardiomyopathy.

There currently are no diagnostic tests or treatments for progeria which remains relentlessly progressive and fatal. Although Hutchinson (1886) and Guilford (1904) did describe the disorder, it was recorded that on "March 19, 1754, died in Glamorganshire of mere old age and a gradual decay of nature at 17 years and 2 months, Hopkins Hopkins, the little Welshman.... He never weighed more than 17 pounds but for three years past no more than 12." The term "progeria" is derived from the Greek word for old age, "geras."