Huntington’s disease

Huntington’s disease, also known as Huntington’s chorea, is a rare inherited neurodegenerative disease. It is named after physician George Huntington, who described the disease in 1872.

It is due to neuron degeneration, leading to uncontrollable movements, loss of intellectual abilities, and emotional alterations. It specifically affects cells in the basal ganglia, deep brain structures that play several major roles, such as movement coordination. The outer surface of the brain, or cortex, is also affected; this part of the brain controls thought, perception, and memory.

Most patients develop Huntington’s disease during adulthood, between their fourth and fifth decades of life. Initial symptoms may include irritability, depression, small involuntary movements, deficient coordination, and difficulty learning new information or making decisions. Many patients develop involuntary spasmodic movements or small muscle contractions (fasciculations); these symptoms are known as chorea. Patients who suffer from this disease also show bradykinesia, which is a term for mild slowness when initiating voluntary movements. As the disease progresses, symptoms become more evident. Patients gradually show trouble walking, speaking, and swallowing food, leading to weight loss. In these cases, patients live around 15-20 years.

Around 10% of people develop symptoms before age 20. These people also show movement issues and mental and emotional swings. Other symptoms include slow movements, clumsiness, rigidity, impaired speech, and drooling. In this type of patients, the disease tends to progress more quickly than in the case of the adult form: individuals usually live for 10-15 years from the onset of symptoms.

There is no cure for Huntington’s disease. The goal of the treatment is to slow disease progression and to help patients manage by themselves as long as possible, as well as mitigating the most severe symptoms. Medication varies depending on symptoms. Dopamine blockers are commonly used and seem to help reduce abnormal movements. Other drugs such as haloperidol, tetrabenazine, and amantadine are used to control additional movements.

Most Huntington patients do not die as a consequence of this disease, but due to health problems derived from the weakness it causes, mostly by choking, infections, and heart failure.

This disease is caused by a mutation in the HTT gene, which encodes a protein known as huntingtin. This mutation leads to the generation of an altered form of the protein, leading to neuron death in some parts of the brain.

The mutation consists of the abnormal repetition of a DNA segment known as CAG trinucleotide. Usually, the CAG segment is repeated between 10 and 35 times within the gene. In patients with this disease, this segment is repeated between 36 and more than 120 times. Individuals with 36 to 40 CAG repeats may or may not develop signs and symptoms of this disease, while those with over 40 repeats almost always develop them.

This disease affects approximately one in 10,000 people in most European countries. In Spain, for example, around 4,000 people suffer from Huntington’s disease. This disorder seems to be less common in other populations, such as the Japanese, Chinese, and African ones.

This disease follows an autosomal dominant inheritance pattern, which means that one copy of the altered gene is sufficient to cause the disease. The affected individuals usually inherit the defective gene only from one affected parent, and the disease is usually present in all generations within a family. In rare cases, an individual with the disease may not have an affected parent. The disease can be inherited and developed by men and women equally.

When the altered HTT gene is transmitted from one generation to the next, the number of repeats of the CAG trinucleotide usually increases. An earlier onset of the disease, such as patients presenting with symptoms before age 20, is often associated with a high number of repeats.

A genetic counseling consultation  is recommended when there is a family history of Huntington’s disease, with the aim of performing genetic testing and determining the probability of developing the disease, which will allow following up on its progression and providing the most suitable treatments for symptom control.

A genetic counseling consultation is also recommended to future parents who suffer from the disease or are aware of cases in the family; in this way, they can know the risk of transmitting the disease to their offspring, perform the genetic testing that are deemed necessary, and take the appropriate prevention measures.

ACHE – Spanish Huntington’s Chorea Association.

Huntington.es – Spanish regional associations listed by the Spanish Huntington’s Chorea Association.

IHA – International Huntington Association