The disease progresses slowly over a 10- to 20-year period and eventually robs the affected individual of the ability to walk, talk, think, and reason. Huntington’s disease usually appears between the ages of 30 and 50. It affects both the basal ganglia, which controls coordination, and the brain cortex, which serves as the center for thought, perception, and memory.
The most recognizable symptoms include involuntary jerking movements of the limbs, torso, and facial muscles. These are often accompanied by mood swings, depression, irritability, slurred speech, and clumsiness. As the disease progresses, common symptoms include difficulty swallowing, unsteady gait, loss of balance, impaired reasoning, and memory problems. Eventually, the individual becomes totally dependent on others for care, with death often due to pneumonia, heart failure, or another complication.
Diagnosis consists of a detailed clinical examination and family history. Brain scans may be helpful. The identification in 1993 of the gene that causes Huntington’s has simplified genetic testing, which can be used to help confirm a diagnosis. Researchers and genetic counselors, however, have established specific protocols for predictive genetic testing to ensure that the psychological and social consequences of a positive or negative result are understood. Predictive testing is available only for adults, though children under the age of 18 may be tested to confirm a diagnosis of juvenile-onset Huntington’s disease. Prenatal testing may be performed. The ethical issues of testing must be considered, and the individual must be adequately informed, because there is no effective treatment or cure, although medications are available to help control some of the symptoms.
The Huntington’s disease mutation is an expanded triplet repeat — a kind of molecular stutter in the DNA. This abnormal gene codes for an abnormal version of the protein called huntingtin. The huntingtin protein, whose normal function is still unknown, is widely distributed in the brain and appears to be associated with proteins involved in transcription (turning genes on), protein turnover, and energy production. Scientists suspect that Huntington’s disease is caused by the gain of a new and toxic function among these proteins.
Cell and animal models can replicate many features of the disease and are now being used to test new theories and therapies. Although no effective treatments for slowing disease progression currently exist, clinical and observational trials are being conducted. Any of these may yield an effective treatment that would slow the progression or delay onset of the disease while researchers continue working toward a cure.