Progeria, also known as Hutchinson-Gilford Progeria syndrome, is a very rare genetic disorder that causes premature aging and the hardening of the arteries in children. This disorder was first described in 1886 by Dr. Jonathan Hutchinson in England and then in 1897 by Dr. Hastings Gilford. This disorder has been documented in only 130 individuals world wide and occurs in 1 in every 4-8 million births.
Children with this disorder appear normal after birth but begin showing signs of progeria after 12-24 months of age. Characteristics of progeria include a sudden slowing of growth, little weight gain, loss of hair (including eyebrows and eyelashes), enlargement of the head (macrocephaly), bulging eyes, a small narrow face with a small lower jaw, narrow beaked nose, brittle bones, and thin, dry scaly skin with visible veins. Because of the hardening of the arteries, individuals with progeria develop heart disease and have irregular heart beats, high blood pressure, and an enlarged heart.
All children with progeria, regardless of ethnic background, have the same physical characteristics such as very short stature, thin bodies with thin limbs, and large heads with bulging eyes. The average lifespan for an individual with progeria is 13-18 years. Cause of death for children with progeria is exclusively cardiac arrest in the form of heart failure or strokes caused by the rapid hardening of the arteries which leads to the restricted blood flow to the heart.
The cause of progeria is a mutation in the gene known as LMNA. The LMNA gene is responsible for making a protein known as Lamin-A. The Lamin-A protein is an important element for the structural support of the nuclear envelope, which is what holds the nucleus in place inside of each cell. In progeria, the LMNA gene is mutated and produces an incorrect form of Lamin-A. This incorrect form of Lamin-A, which is also called progerin, is not stable and results in a poorly constructed nuclear envelope that does not support the nucleus of the cell. This results in early cell death which is what causes the occurrence of the rapid aging process of the children with progeria. Individuals whose bodies are loosing cells due to rapid cell death cannot support normal tissue growth, thus resulting in rapid deterioration of the body and heart health. This mutation was identified in 2003 and was a monumental discovery for scientists as, until then, the cause of progeria was unknown.
The LMNA mutation is caused spontaneously and is not passed down from parent to child. Children suspected of having progeria are diagnosed with blood tests and screenings designed to look for the mutated LMNA gene. The LMNA gene is located on chromosome 1 and the mutated version that causes progeria has a specific sequence that is unique to individuals with the disorder.
There is no known cure for children with progeria. However, newly developed drugs, known as FTIs (Farnesyltransferase Inhibitors), have shown promise in reducing cell damage and death in studies using mouse cell models. The FTI drugs keep the abnormal form of Lamin-A from creating poorly constructed nuclear envelopes in cells. The mice treated with these drugs show an increase of weight gain, live longer, and have a greater quality of life.
Another drug that has shown promise in mouse studies is rapamycin. Rapamycin is already FDA approved for treating cancer and has been found to reverse damage to the nucleus and nuclear envelope in cells affected by the abnormal form of Lamin-A.
Fortunately, children living with progeria today have a better chance at possibly living a longer and healthier life than those in the past. Thanks to the increased amount of scientific exploration in the fields of cellular aging and death and the new discoveries with drugs such as the FTIs and rapamycin, these children may have an increased life span. The study of progeria also sheds light on the normal aging process of cells in healthy individuals as progeria paints a very detailed illustration on the life and death of cells and the actions that take place on the genetic level.
