Huntington's disease is a rare genetic disorder that primarily affects the central nervous system. Originally it was called Huntington's "chorea", from the Greek "χορεία" which means "dance", because the involuntary, abrupt and almost jerking movements that can occur in the limbs, face and trunk are reminiscent of a dance.
Today, we prefer to use the broader term "disease" because in addition to movement disorders it also causes others.
Huntington's disease is caused by a defective gene inherited from a parent and is characterized by the progressive degeneration of nerve cells (neurons) present in specific areas of the brain which are then damaged. Brain damage worsens over time to compromise movement, cognitive abilities (perception, awareness, thinking, judgment) and behavior.
Huntington's disease generally manifests itself in adulthood, between 35 and 50 years of age and, more rarely, before the age of 20 (5-10% of cases) or late in life. It affects men and women equally. Those who have close family members who are already ill (family history) can inherit it.
The disease worsens over the course of 10-25 years from the moment the first complaints (symptoms) appear. The later stages lead to those affected losing their autonomy and needing full-time nursing care.
In Europe, about 4-6 people per 100,000 individuals are affected; however, it is believed that the number of people carrying the Huntington gene, but not yet manifesting the disorder, may double.
In some non-European areas the disease is more widespread and in one region of Venezuela there are 18,000 people affected, all descendants, in the course of 10 generations, from a single sick woman.
Death is usually due to a secondary cause, such as heart failure, pneumonia or other infections.
The disorders (symptoms) caused by Huntington's disease include, in addition to abnormal movements, psychiatric problems and difficulties with behavior, nutrition and communication.
In sick people, disorders can begin to appear at any age but most problems occur between the ages of 35 and 55.
The disease usually progresses and worsens over the next 10-25 years.
Signs and disorders (symptoms) can vary from individual to individual and there is no typical pattern. Early disorders, such as personality changes, mood swings and unusual behavior, are often initially overlooked and attributed to other reasons. . Some individuals with Huntington's disease may not recognize that they have problems.
Behavior change is often the first disorder (symptom) to appear and can be represented by:
- lack of emotion and empathy
- periods of aggression and excitement, alternating with depression and apathy, antisocial behavior and anger
- difficulty concentrating on more than one task and managing complex situations
- irritability and impulsiveness
A person with Huntington's disease may appear to have no desires, may lack initiative, focus and interest in hygiene and self-care.
Many sick people develop depression, not just as a result of discovering the disease but because of it. Symptoms of depression include:
- mood drop
- decreased self-esteem
- lack of motivation or interest in things (apathy)
Some sufferers, although rarely, may have obsessive behaviors and personality disorders.
Huntington's disease involves movements and is initially characterized by their accentuation (hyperkinesis). Disorders (symptoms) begin with mild uncontrolled facial movements, such as tics, twitching or grimacing, and restless movements of the limbs and body that can be the cause of skidding and falling.
The onset of motor disorders can occur both in conditions of rest (lying down or sitting) and during normal activities.
As the disease progresses, uncontrolled gestures become more frequent and extreme while, in the more advanced phase, they become slow (bradykinesia), the muscles stiffen and the person tends to assume unnatural positions (dystonic).
People with Huntington's disease tend to lose weight while maintaining a good appetite. Eating becomes strenuous, frustrating due to the loss of control of the muscles of the mouth and throat. Lack of coordination can lead to spilling or dropping food, and swallowing can become difficult with increased risk of choking (from both food and drink).
Sometimes, the intervention of an expert in speech and swallowing disorders (speech therapist) may be necessary and, in severe cases, nutrition may be considered by inserting it into the stomach, passing through an incision made on the abdominal wall, of a small tube (percutaneous endoscopic gastrostomy, PEG) that allows nutrition.
Communication difficulties and progressive loss of cognition are part of the degeneration of Huntington's disease.
Affected people often have difficulty translating thoughts into words and delivering a speech.They may understand what they are told but may not be able to respond or communicate that they understand. As the disease progresses, they become less reactive and communicate less and less.
Huntington's disease, especially in the early stages, can cause problems with sexual intercourse. Patients often lose interest in sex; less frequently they express inappropriate sexual intercourse.
Advanced stages of the disease
In the advanced stages of Huntington's disease, the affected person will be totally dependent on others and in need of full-time nursing care.
Death usually occurs from a secondary cause, such as pneumonia or some other infection.
Juvenile Huntington's disease
Juvenile Huntington's disease is rare and can occur in people under the age of 20.
The most common signs are:
- rapid decline in academic performance
- changes in handwriting
- movement problems such as slowness, stiffness, tremors or muscle twitching (similar to the characteristics of Parkinson's disease)
Huntington's disease is caused by a defective gene that is passed on to offspring.
Genes and chromosomes
The gene is the fundamental hereditary unit of living organisms, it is made up of the so-called deoxyribonucleic acid (DNA) and is found on strands called chromosomes. Human cells have 46 chromosomes (23 pairs) and each human being has two copies of each gene. one on each chromosome of the pair.
The faulty gene that causes Huntington's disease is found on chromosome number four. The copy of the normal gene produces a protein, called huntingtin, but the defective gene contains an abnormal region with so-called "CAG repetitions"Produces a" faulty "form of huntingtin. The cells of certain parts of the brain, more precisely of the so-called basal ganglia and of cerebral cortex, are very sensitive to the effects of defective huntingtin, which is toxic and causes neuronal death.
Areas of the brain damaged by hunting normally control movement, thinking and behavior. For this reason, patients gradually lose these functions.
It is not yet clear exactly how defective huntingtin affects brain cells and why some are more sensitive than others.
Inheritance of Huntington's disease
A parent with Huntington's disease has one normal copy and one defective copy of the gene. The child will only inherit one of these genes, therefore, he will have a one in two chance of receiving the defective gene and developing Huntington's disease.
Each child of Huntington's disease parents has a 50% chance of inheriting the defective gene:
- identical probability both in the case that it is the mother who is ill and that it is the father
- being male or female does not affect the likelihood of having inherited the mutated gene which, therefore, is always 50%
- child who has not inherited the mutated gene will never develop the disease nor will he ever pass it on to his own children
This inheritance model is called autosomal dominant. Dominant because only one defective gene is enough to develop the disease, autosomal because the defective genes are not found on the sex chromosomes which are, instead, defined heterosomes.
In approximately 3% of Huntington's disease cases, no sick family members are present. This could be due to adoption cases or the death of the sick parent before the disease was discovered. In rare cases, the cause is to be found in a new expansion in the gene.
In the presence of disorders (symptoms) similar to those caused by Huntington's disease, the family doctor may ask to undergo a specialist visit, usually by the neurologist, to evaluate the appropriateness of further investigations.
The specialist will examine the disorders (symptoms) to establish the likelihood of facing Huntington's disease rather than other similar diseases.
During the visit, the neurologist will examine some physical functions such as, for example, eye movements, balance, control, movement and gait, speech and cognitive skills.
Genetic testing can be used to confirm whether or not the disorders are caused by Huntington's disease.
The mutation of the gene that causes Huntington's disease can be identified by analyzing the DNA obtained from a simple blood sample.
Children of a person with Huntington's can undergo genetic testing to see if they have inherited the defective gene. In this case, the development of the disease is certain but it is not possible to establish at what age it will manifest itself.
The test result may take 2-4 weeks to wait.
CT and MRI
Computed axial tomography (CT) and nuclear magnetic resonance imaging (MRI) can be used by doctors to highlight changes in areas of the brain.
Although there may be no specific changes in the early stages of Huntington's disease, doctors can use these techniques to rule out the presence of other diseases.
Nuclear magnetic resonance imaging provides more detailed images and is more sensitive in identifying changes in the brain. Claustrophobic people, however, may have difficulty undergoing it because the examination usually takes place in a closed tube open only at the ends. Open equipment is available in some healthcare facilities.
There is no cure for Huntington's disease and its evolution over time cannot be reversed or slowed down.
Some features of the disease can be managed with:
- speech therapy and occupational therapy to help communication and daily life management
- regular exerciseActive people tend to feel better both physically and mentally than those who don't exercise
- use of specific supports to help those with coordination difficulties to walk independently
- use of drugs
Huntington's disease medications
Available drugs are designed to control disorders, particularly those related to movement and psychiatric ones.
Most of the medicines used have undesirable effects (side effects) although it can sometimes be difficult to determine whether they are related to the disease or the effect of the drug.
Among the drugs used in the treatment of disorders:
- antidepressants to treat depression
- SSRI antidepressants
- tricyclic antidepressants
- other types of antidepressants
- mood stabilizers for the treatment of irritability and mood swings, some of these medicines cannot be used during pregnancy
- drugs to control involuntary movements
- antipsychotics, also used in the control of delirium and outbursts of violence
- medicines that reduce the amount of dopamine
Given the side effects of antipsychotic drugs, the lowest possible dose is used.
Prenatal test (during pregnancy)
If a person with Huntington's is expecting a baby, they can do a genetic test at 11th week of pregnancy (prenatal test) to see whether or not the fetus has inherited the defective gene.
It is a very personal choice that needs careful evaluation and the advice of a genetic counseling team.
In the event that one of the members of a couple is at risk for Huntington's disease but does not want to know if she has the defective gene and the couple wishes to have healthy children, one option to be sure could be PGD.
Preimplantation Genetic Diagnosis (PDG) it implies the use of fertilization in vitro (IVF), a technique that involves the fertilization in the laboratory of the eggs taken from the woman with the man's sperm. Subsequently, preimplantation genetic diagnosis will be performed on the developing embryos to check if the defective gene is present.
Only embryos that are healthy, without the gene responsible for the disease, will be implanted in the woman's uterus; in this case, there is no risk that the child will develop Huntington's disease.
PGD is not a simple procedure, and it raises a number of questions that need to be considered in detail. In Italy, patients have the right to be "informed, at their request, on the state of health of the embryos produced and to be transferred to the" uterus ", pursuant to art. 14 paragraph 5 of Law 40/2004.
Genetic counseling with an expert will help couples understand the options available in Italy.
The family doctor is the reference figure for the patient and to help the family find the facilities available in Italy for support.
Daily help for people with Huntington's disease includes physical therapy, occupational therapy, and speech therapy.
Huntington's disease puts the interpersonal relationships of the affected person in great difficulty and also has a strong impact on his family: it is painful to see the deterioration of the mind of a loved one and how normal daily actions, such as dressing and eating, can become frustrating. and tiring.
The types of help described below are intended to relieve tension due to the disease by improving the patient's quality of life.
Speech therapy is able to improve memory and communication skills through speech therapy or by teaching alternative methods of communication.
Sometimes, aids that allow you to interact without talking can be useful.
Speech therapy can also help with swallowing problems.
People with Huntington's disease need a high calorie diet; the intervention of a dietician can help develop an adequate diet.
Food should be made easy to chew, swallow and digest; it can be cut into small pieces or in the form of puree to avoid choking. The use of straws can facilitate the ingestion of liquids.
During the later stages of the disease, it may be necessary to feed the patient with a percutaneous endoscopic gastrostomy which consists in inserting a feeding tube directly into the stomach.
An occupational therapist can help with common daily activities. The home can be adapted to make life easier for the sufferer, to prevent the risk of falls or, for example, to prevent the possibility of a fire occurring.
The shower, tub, chairs and bed may need to be modified and adapted to the patient's needs, and a wheelchair may also be required.
The daily maintenance of physical exercise is very important because it promotes a state of both physical and mental well-being in the patient.
The physiotherapist intervenes on mobility and balance using a wide range of interventions, including:
- physical exercise
An experienced physical therapist can be advised by your family doctor or by social services.
Your primary care physician or specialist will be able to provide guidance on organizations that offer support to Huntington's patients and their families.
NHS. Huntington "s disease (English)
40 of 19 February 2004.Rules on medically assisted procreation (Official Gazette no. 45 of 24 February 2004)
Preimplantation Genetic Diagnosis (PGD). Preimplantation diagnosis after the approval of law 40/2004