In the mid-1800s English doctor John Langdon Down was appointed director of a home outside London for mentally handicapped children, where he studied their symptoms. In 1862 he described the case of one of his wards who was short and had stubby fingers and unusual eyelids. The boys condition was later labeled with his surname. But the genetic cause of Down syndrome was not uncovered for another century. In 1959 French pediatrician Jrome Lejeune discovered that these children have three copies of chromosome 21, instead of the standard two.
For too long, people with Down syndrome, or trisomy 21, have been dismissed as retarded and thus incapable of having rich lives. But that view has begun to change. Psychologists, doctors and special-education teachers now realize that a diagnosis at infancy does not necessarily mean a child will have few options in life--as long as he or she receives special training early. And socially, Down syndrome children are finally being accepted as unspectacular, everyday kids, in part thanks to the 1990s hit ABC television series Life Goes On, starring an actor with Down syndrome, Chris Burke, who today is 41.
Physical limitations continue to challenge these individuals. Poor muscle tone (which often causes the tongue to protrude from the mouth); joint trouble; pale, sensitive skin; and vision, hearing and thyroid problems are prevalent. About half suffer from congenital heart defects. But medical progress in the past two decades has doubled the average life expectancy from 25 to 50 years. For those without heart defects, life expectancy is even higher. Yet for most, a rewarding mental and social life is their greatest desire--and their greatest challenge.
Third Copy Interference
Trisomy 21 is the most common chromosomal abnormality in humans. It affects one in every 800 to 1,000 live births. Today more than 350,000 Americans have Down syndrome. But why does having three copies of chromosome 21 cause the condition? With a completed map of the human genome, researchers are in hot pursuit of an answer.
Soon after scientists in the Human Genome Project finished describing chromosome 21 in 2000, they confirmed that within this chromosome are the genes that cause both Down syndrome and Alzheimers disease. Neurologists had previously discussed a connection between the two disorders, because both involve an inadequate production of the neurotransmitter acetylcholine, one of the brains messenger molecules. In a 2003 research review, Nancy Roizen of the Cleveland Clinic and David Patterson of the University of Denver focused on a particular gene that is crucial to energy production and oxygen utilization inside cells. They speculated that a defect in this system leads to the production of aggressive oxygen free radicals--molecules that damage cells--which may play a role in both Down syndrome and Alzheimers.
In 2004 Guilherme Neves and Andrew Chess, now at the Center for Human Genetic Research at Massachusetts General Hospital, tracked the roles played by other genes on chromosome 21--in this case using a fruit fly as the model. They found a gene--dubbed Dscam (Down syndrome cell adhesion molecule)--that appears to give every nerve cell a unique identity during prebirth development, making sure that each cell ends up in the right location in the brain and body. Neves and Chess hypothesize that a different version of the gene may affect humans similarly. Because people with trisomy 21 possess an additional copy of this gene, the oversupply may hinder the establishment of correct connections among brain cells during fetal development.
Shortly before birth, the brain starts checking over its entire network and sorting out the superfluous connections, which are then pared down. But in one explanation, with trisomy 21 many of the unproductive connections endure. They constitute dead ends that slow the physical growth, learning and thought processes of people with Down syndrome.