Naxos disease is a hereditary disease that is inherited in an autosomal recessive manner. Worldwide, it is a very rare hereditary disease, but not on the Greek island of Naxos, where it is very common and was also first described by a doctor. The dangerous thing about Naxos disease is that it always leads to serious heart problems and often sudden cardiac death over the years. That is why it is important to prevent it. For this purpose, various medications, the timely use of a cardioverter defibrillator and if all these measures can no longer help, even a heart transplant can be considered.
What is Naxos disease?
Naxos disease was first described in 1986 by Nikos Protonotarios, a Greek cardiologist and a group of researchers working with him. On the island of Naxos, the probability of getting this hereditary disease is 1: 1000. There are also more frequent cases of Naxos disease on other islands in the Aegean Sea, in Turkey, Israel or Saudi Arabia. Worldwide, this hereditary disease is rather rare. Already in freshly born babies it can be recognized by very woolly hair that they might suffer from Naxos disease. In the course of the first year of life, strange-looking keratoses form on the soles of the feet and palms of the hands. Naxos disease usually becomes dangerous only in young adulthood, when a so-called dilated cardiomyopathy increasingly develops, which can lead to severe cardiac arrhythmias, palpitations, overall right heart failure, and later sudden cardiac death.
Causes
The causes of the health problems associated with Naxos disease are due to impaired cell adhesion. This is due to a mutation of the JUP gene, which is located on chromosome 17 and, in turn, on gene locus q21. Five amino acids are altered as a result, which in turn leads to 56 other amino acids being cut off from a domain. This results in incorrect folding of the corresponding gene product. This error, in turn, is detected by the body’s own protein quality control system and the gene product is then proteasomally degraded. This leads to cell death. The dead cells in turn are then replaced by fatty tissue or fibrous tissue. This is increasingly life-threatening, especially in the case of cardiac muscle cells lost in this way.
Symptoms, complaints, and signs
The first signs of Naxox disease can be seen when an infant is born, namely in the particularly woolly hair. Complaints are not yet present at this age. Very early, namely in the course of the first year of life, the cell changes typical of Naxos disease appear on the soles of the feet and palms of the hands, so-called keratoses. A white scaling is typical for these keratoses. It is not until adulthood that the dangerous heart problems develop. These include dizziness, palpitations, severe circulatory problems up to circulatory collapse, a right heart failure that can then be easily detected by the doctor, and if it gets really bad, sudden cardiac death.
Diagnosis and course of the disease
The diagnosis is easy to make and possible even in infancy, because the external signs of Naxos disease are easy to recognize. Absolute certainty is provided here by DNA analysis. Over the years, the typical heart problems then occur in adulthood, which become progressively worse and must be treated without fail to improve the patient’s life expectancy.
Complications
In the worst case, Naxos disease can lead to the death of the patient. This usually occurs in the form of sudden cardiac death and can significantly reduce the life expectancy of the affected person. In emergency cases, the patient’s life may still be saved with a defibrillator. In severe cases, however, this requires the transplantation of a heart so that the patient can continue to survive. As a rule, patients suffer from scaling of the skin in the area of the hands. Sometimes they also experience palpitations and dizziness. Sufferers feel weak and generally ill with this disease and also suffer from a reduced ability to cope with stress. Circulatory collapse can also occur with Naxos disease, leading to loss of consciousness.Furthermore, Naxos disease eventually leads to complete heart failure, which results in the patient’s death. Naxos disease is treated with the help of medications. In severe cases, transplantation of the heart may be necessary. Complications may arise during the operation itself. As a rule, the life expectancy of the affected person is significantly reduced by Naxos disease.
When should you see a doctor?
If newborn infants show noticeable head hair immediately after birth, this may be the first sign of an existing irregularity. Although there are no other symptoms at this stage, woolly hairs are characteristic of Naxos disease and need to be examined more closely by a doctor. If disturbances of cardiac activity develop in the further growth process, there is cause for concern. Rapid heartbeat, cardiac arrest, abnormal blood pressure or circulatory collapse must be presented to a physician as soon as possible. Since the condition can lead to sudden cardiac death if left untreated, a visit to the doctor should be made at the first abnormalities. Sleep disturbances, an unusual day-night rhythm, deficits in concentration and attention, and rapid fatigue should be examined and treated by a physician. If there is a loss of consciousness, an emergency physician must be called. Bystanders must take first aid measures until the doctor arrives. Otherwise, the affected person may die prematurely. Low resilience, inner restlessness and a general feeling of weakness are further signals of an existing health impairment. They should be assessed by a physician. In the case of dizziness, unsteadiness of gait and a lack of physical activity, a physician should be consulted. If there are members of the family already diagnosed with Naxos disease, physicians should be made aware of this during pregnancy.
Treatment and therapy
The genetic changes caused by Naxos disease cannot be treated. It is only possible to treat the symptoms of the heart problems. Here, various medications can be considered first, which may be helpful. Depending on the severity of the heart problems, these include, for example, antiarrhythmics, beta blockers, diuretics or ACE inhibitors. Very often, a cardioverter defibrillator is used before the age of 35, which can help alleviate heart problems for a longer period of time. Often, however, in Naxos disease, it is not possible to avoid heart transplantation at an older age as well, in order to keep the patient alive as long as possible. There are no other options for treatment and therapy of Naxos disease so far. Nevertheless, by the above-mentioned measures, the people who have this genetic disease can reach a fairly old age if treated in time.
Prospect and prognosis
Naxos disease offers a relatively poor prognosis. Patients often suffer sudden cardiac death. Implantation of a pacemaker is the only way to avoid severe complications. The average life expectancy after a successfully performed heart transplantation is currently ten years. In the best case, patients survive with the donated heart for up to 30 years. The pronounced physical abnormalities also represent a psychological burden. Affected patients are always reminded of their disease by the lesions and bleeding and are often socially ostracized. In addition, there are physical complaints such as dizziness or changes in blood pressure. In the long term, a right heart failure develops, which is accompanied by a reduced performance capacity. In many cases, the consequence is sudden cardiac death, which cannot be prevented in the long term even by the measures mentioned above. The use of beta-blockers, ACE inhibitors and other drugs is also associated with risks that further worsen the prognosis, partly because patients have to take these drugs throughout their lives. Life expectancy is greatly reduced. Many patients die before the age of 50. Also because of the many accompanying symptoms, the prognosis in Naxos syndrome is generally rather negative.
Prevention
Anyone born with Naxos disease can do nothing about the disease itself through prevention.It is only possible to counteract the later heart problems caused by this disease by appropriate prevention. Another form of prevention against Naxos disease is the timely identification of the relevant risk groups through appropriate screening of the population in those places in the world where there is a high incidence of inheritance of Naxos disease. In this way, by identifying heterozygous carriers, we can prevent the spread of this hereditary disease. In the case of Naxos disease, the probability of giving birth to an infant suffering from this disease is 25 percent in this case of autosomal recessive inheritance with two mutation carriers, mother and father. Another 25 percent of these children will be completely healthy and again 50 percent will be renewed mutation carriers. It is therefore very important, in families in which this disease has already occurred, to determine preventively whether the descendants are mutation carriers or not and then to ensure that, if possible, no further mutation carriers are born into the world. This is the only way to contain this hereditary disease.
Follow-up
In most cases, only very few and usually very limited aftercare measures are available to the affected person for Naxos disease, since it is a hereditary disease that cannot be completely retreated by a physician. For this reason, the patient should consult a doctor at the first signs of the disease in order to prevent the occurrence of further complications. If there is a desire to have children, genetic counseling can also be performed to prevent the recurrence of Naxos disease in the descendants. With this disease, most patients are dependent on taking various medications. Here, the instructions of a physician should always be followed, and the affected person should first consult a physician if there are any questions or if anything is unclear. Likewise, attention should be paid to correct dosage and regular intake. Furthermore, regular checks and examinations of the internal organs are necessary, whereby the heart in particular should be checked. In some cases, Naxos disease can reduce the life expectancy of the affected person, although the further course is highly dependent on the time of diagnosis.
Here’s what you can do yourself
Naxos disease is primarily treated with medication and surgery. Sufferers can take some measures themselves to support treatment and make everyday life with the disease easier. First of all, dietary measures are necessary. Those affected must eat a healthy diet and avoid foods that could put additional strain on the cardiovascular system. These include salt and glutamate, for example, but also saturated fatty acid. Particularly spicy or irritating foods should be avoided. Caffeine, alcohol and cigarettes should also be avoided. Which diet makes sense in detail should be discussed with a nutritionist. Naxos disease can also be treated by exercising and avoiding extreme physical stress and endurance sports. Other self-help measures focus on going for regular screenings and following the doctor’s guidelines. Patients who already have a pacemaker should follow the usual tips and, for example, keep their distance from electronic devices. Contact sports must also be avoided. As Naxos disease becomes more severe as it progresses, there is a permanent threat of deterioration in health. Therapy can help affected individuals accept this fact and lead a full and happy life despite their reduced life expectancy.
