Hoffmann's disease - what is it?

Werdnig-Hoffmann disease is an extremely severe pathology, which is accompanied by amyotrophy, the gradual destruction of the main nerve fibers of the spinal cord, and, accordingly, muscle atrophy. It is immediately worth noting that this is a hereditary genetic disease that is transmitted in an autosomal recessive manner.

What is Werdnig-Hoffmann disease?

This is a neurological disease accompanied by the gradual destruction of the main innervating structures of the nervous system. For example, demyelination of the anterior roots of the spinal cord is often observed. In addition, the disease also affects some cranial nerves.

Of course, damage to nerve fibers affects the condition of the muscles. However, this disease is characterized by the so-called bundled muscle lesion, in which part of the muscle tissue retains the ability to contract, while individual “bundles” atrophy.

Werdnig-Hoffmann spinal atrophy manifests itself in childhood. Today, it is customary to distinguish three main forms of the disease.

Congenital Werdnig-Hoffmann disease and its symptoms

As a rule, the first symptoms of this form of the disease are noticeable already in the first days after the birth of the child. The baby has flaccid paresis of the limbs. The cries of sick children are weak and barely audible, in addition, their feeding process is disrupted.

As the child grows, a lag in physical development may be noticed. Sick children cannot hold their heads up and can neither sit nor stand. Only in rare cases is the baby able to hold the body in an upright position, but this ability also disappears quite quickly as the nerve fibers are destroyed.

The course of the disease in question is malignant, and the degeneration of nerve endings progresses rapidly. Not only skeletal muscles, but also the fibers of internal organs are susceptible to atrophy. The diaphragm is often affected, leading to the development of respiratory failure. Unfortunately, children with this condition live (on average) until they are nine years old.

Early Werdnig-Hoffmann disease

The main signs of the disease appear in the second half of life. The first few months the child’s physical development is quite normal - the baby learns to hold his head up and sit down, sometimes he can even sit up on his own. But all these skills are lost after the disease is activated. By the way, the syndrome is often provoked by an infection.

Finger tremors and tendon contractures are the first symptoms of nerve fiber destruction. Subsequently, muscle atrophy and paralysis develop. The average life expectancy of patients is from 14 to 16 years.

Late form of Werdnig-Hoffmann disease

This disease is more mild. As a rule, a child develops quite normally until the age of two. The baby learns to sit, stand and walk. Only over time do parents begin to notice some deviations.

First, the sick child's gait changes - he walks with his legs strongly bent at the knees, and often falls, unable to maintain balance. As the pathology develops, some changes in the skeleton can be noticed, in particular, deformation of the chest. Werdnig-Hoffmann syndrome is characterized by severe hand tremors, decreased muscle tone, and the disappearance of basic unconditioned reflexes.

In most cases, by the age of 10-12 years, the child completely loses the ability to move independently. However, in this case, patients live up to 20, and sometimes up to 30 years.

Spinal amyotrophy Werdnig-Hoffmann (acute malignant infantile spinal amyotrophy Werdnig-Hoffmann, spinal amyotrophy type I) is a hereditary disease of the nervous system, characterized by the development of muscle weakness in almost all muscle structures of the body. Leads to impairment of the ability to sit, move and self-care. There are no effective treatments for the disease. Prenatal diagnosis helps to avoid the birth of a sick child in the family. From this article you can learn about how this disease is inherited, how it manifests itself and how you can help such patients.

The disease is named after the two scientists who first described it. At the end of the 19th century, Werdnig and Hoffman proved the morphological essence of the disease. They assumed the only such form of the disease. However, in the 20th century, Kueckelberg and Welander described a different clinical form of spinal amyotrophy, which had the same genetic cause as Werdnig-Hoffmann spinal amyotrophy. Today, the concept of spinal amyotrophy combines several clinically different forms of the disease. But they are all associated with the same hereditary defect.

Causes of spinal amyotrophy

The disease is hereditary. It is based on a genetic mutation in the 5th human chromosome. The gene responsible for the production of the SMN protein undergoes mutation. The synthesis of this protein ensures the normal development of motor neurons. If a mutation develops, the motor neurons are destroyed or are underdeveloped, which means that the transmission of impulses from the nerve fiber to the muscle is impossible. The muscle doesn't work. Consequently, all movements associated with a non-working muscle are not performed.

The incorrect gene has an autosomal recessive pattern of inheritance. This means the following: in order for spinal amyotrophy to develop, the coincidence of two mutant genes from the mother and from the father is necessary. That is, the mother and father of the child must be carriers of the pathological gene, but at the same time they are not sick due to the simultaneous presence of a healthy dominant (predominant) gene (genes for each person are paired). If the mother and father are carriers of a pathological gene, then the risk of having a sick child is 25%. It is estimated that approximately every 50th person on the planet is a carrier of the mutant gene.

Symptoms

To date, 4 forms of spinal amyotrophy are known. They all differ in the period of onset of the disease, some symptoms and life expectancy. Common to all forms is the absence of sensory and mental impairment. The functions of the pelvic organs are never affected. All symptoms are associated only with damage to the motor sphere.

Spinal amyotrophy type I

There may be disturbances in sucking and swallowing, and difficulty moving the tongue. Fasciculations may be visible on the tongue itself (involuntary muscle contractions, “waves” running across the tongue), and it itself looks atrophied. The baby's cry is sluggish and weak. If the pharyngeal reflex decreases, problems with feeding arise, resulting in food entering the respiratory tract. And this causes aspiration pneumonia, from which the child can die.

Damage to the diaphragm and intercostal muscles is manifested by impaired breathing. Initially, this process is compensated, but gradually respiratory failure worsens.

It is characteristic that the facial muscles and muscles responsible for eye movements are not affected.

Such children are lagging behind in motor development: they do not hold their heads up, do not roll over, do not reach for objects, and do not sit up. If some motor skills were able to be realized before the onset of the disease, they will be lost.

In addition to movement disorders, the disease is characterized by chest deformation.

If signs of the disease are visible immediately after birth, then such children often die within the first 6 months of life. If signs appear after 3 months, then the lifespan is slightly longer - about 2-3 years. Inevitably, an infection occurs due to respiratory problems, from which such children die.

Spinal amyotrophy can be combined with congenital malformations: mental retardation, small skull, heart defects, congenital fractures, hemangiomas, clubfoot, undescended testicles.

Spinal amyotrophy type II

This form of the disease occurs between the first 6 months and 2 years of life. Before this, no violations are detected in the child. He begins to hold his head up, roll over and sit, and sometimes walk. And then muscle weakness gradually appears. It usually starts with the thigh muscles. Walking gradually becomes impossible, tendon reflexes decrease and are lost. Muscle weakness progresses slowly. All limbs are involved. Muscle atrophy develops. The process can also involve the respiratory muscles. Also, as with type I spinal amyotrophy, facial muscles and eye muscles are not affected. There may be trembling of the hands, twitching of the tongue and limbs. Weakness of the neck muscles is manifested by drooping of the head.

Osteoarticular deformities are very characteristic: scoliosis, funnel chest, dislocation of the hip joint.

This form has a more benign course than spinal amyotrophy type I, but most patients have respiratory problems by adolescence. Poor chest excursion contributes to the development of infections, which can kill the child.

Spinal amyotrophy type III

This form is described by Kuckelberg and Welander. It is considered juvenile spinal amyotrophy. The onset of the disease is between 2 and 15 years.

The first symptom is always unsteady walking due to increasing weakness in the legs. The tone in the legs decreases, muscle atrophy develops (the muscles become thinner), but this is not always noticeable due to the well-developed layer of subcutaneous fat at this age. Children stumble, fall, and move awkwardly. Gradually, movements in the legs become impossible, and the patient stops walking.

Gradually, the disease also affects the upper limbs; the hands are affected later. With this form, weakness of the facial muscles develops, but eye movements are preserved in full. There are no reflexes from those muscle groups that are already involved in the process.

Skeletal deformities are also characteristic: funnel chest, joint contractures.

This form of the disease, with maintenance therapy, allows patients to live up to 40 years.

Spinal amyotrophy type IV

This form of the disease is considered “adult” because it appears after 35 years. Weakness also occurs in the leg muscles, decreased reflexes, and muscle atrophy, which ultimately leads to a complete loss of movement in the legs. In this case, the respiratory muscles are not involved in the process, and there are no breathing problems. Life expectancy in this form of the disease is almost the same as in healthy people. The course is the most benign compared to other forms.

Diagnostics

When symptoms similar to spinal amyotrophy appear, electroneuromyography is performed (spontaneous activity is detected in the form of fasciculation potentials at rest and an increase in the average amplitude of motor unit action potentials).

The question of diagnosis is finally resolved after a genetic study (DNA diagnosis): a gene mutation is found on the 5th chromosome.

In families where there have been cases of such diseases, prenatal (antenatal) DNA diagnostics of the fetus is carried out. If a pathology is detected, the issue of terminating the pregnancy is decided.

Principles of treatment of spinal amyotrophy

Unfortunately, this is an incurable hereditary disease. At the present stage, research is being conducted that may help regulate the synthesis of the SMN protein, but there are no results yet.

The following help alleviate the condition of patients with spinal amyotrophy:

1. periodic course intake of drugs that improve the metabolism of nervous tissue and muscles (Cerebrolysin, Cytoflavin, Glutamic acid, ATP, Carnitine chloride, Methionine, Potassium orotate, Tocopherol acetate, etc.);
2. B vitamins (Milgamma, Neurovitan, Combilipen);
3. anabolic steroids (Retabolil, Nerobol);
4. agents that improve neuromuscular conduction (Proserin, Neuromidin, Galantamine, Dibazol);
5. massage and physical therapy courses;
6. physiotherapy (electrical muscle stimulation, carbon sulfide baths);
7. methods of orthopedic correction (with the development of joint contractures and spinal deformities).

Werdnig-Hoffmann spinal amyotrophy, like other forms of this disease, is a pathology that is inherited. The appearance of the disease in a child is explained by the presence of a mutant gene in both the mother and father. The disease is characterized mainly by muscle weakness, which causes immobility and respiratory problems. The disease is currently incurable.

Genetic diseases affecting the nervous system lead to damage to organs and parts of the body, disrupting their normal functioning. One of them is Werdnig-Hoffman disease. It is quite rare - one case per 7-10 thousand people.

Etiology of Werdnig-Hoffmann disease

Werdnig-Hoffmann disease (spinal muscular amyotrophy) is characterized by pathology of the nerve cells of the spinal cord, which results in the drying out of muscle fibers intertwined with healthy ones. This process is caused by an insufficient amount of protein responsible for the survival of motor neutrons. There are forms of the disease not associated with this pathology, caused by other modifying factors.

Disruption of the functioning of nerve cells leads to the proliferation of connective tissue, which replaces muscle tissue. The patient's swallowing process, musculoskeletal and respiratory functions are impaired. Mental development is not affected. The sensitivity of the parts of the body affected by the disease does not decrease.

Werdnig-Hoffman disease is hereditary, transmitted from two parents who are carriers of the pathological SMN gene, located on chromosome 5. However, they have no symptoms of the disease. Such a couple can give birth to healthy children or also carriers of the gene; the probability of giving birth to a sick baby is 25%.

Famous people with this disease: English astrophysicist Stephen Hawking and Russian IT specialist Valery Spiridonov from Vladimir.

Symptoms of the disease

Signs of the disease directly depend on its form; the study reveals the following clinical indicators:

1. Malnutrition of muscle cells leads to their death. First, the muscles of the trunk are affected, primarily the back, then the process moves to the area of ​​the shoulders, hips, and limbs;
2. increasing pain;
3. decreased muscle tone;
4. muscle twitching;
5. reduction in the diameter of long bones, detected by radiographs;
6. curvature of the spine to one side and backward;
7. established limitation of muscle function (does not bend or relax).

Symptoms indicating the presence of spinal muscular amyotrophy:

1. muscle weakness, manifested in disruption of motor processes;
2. due to thinning of the bones, the limbs become smaller;
3. paucity of facial movements;
4. swallowing and sucking reflexes are reduced or absent;
5. if the intercostal muscles are damaged, breathing is impaired, and as a result, inflammatory and congestive processes in the bronchi and lungs;
6. deformation of the skeletal system in the chest and spine;
7. tremor of hands and feet;
8. inhibition of physical development processes.

Forms and stages of the disease

Spinal muscular amyotrophy in most cases manifests itself in the first year of a child’s life. The earlier, the more severe its course. The mortality rate is high, most children die before the age of 4, rarely before the age of 20. It can also occur in adults. There are three main forms of the disease:

1. Congenital Werdnig-Hoffman disease. The first symptoms appear immediately after birth or during the prenatal period. At the same time, fetal movements subside. The newborn has disturbances in the processes of breathing, sucking and swallowing. The child does not hold his head up, does not roll over, and screams weakly. The course of the disease is severe, acute, life expectancy is short, up to 2 – 2.5 years. However, in some cases, with the help of modern artificial lung ventilation devices and feeding not through a tube, but directly into the stomach, the patient’s life can be extended. The child develops mentally and emotionally without disturbances.
2. The second form, early childhood. The child's development proceeds in accordance with the norms. He begins to hold his head up in time and roll over. Until six months, parents do not notice any symptoms. After an infection, the disease manifests itself in the form of peripheral paralysis of first the lower, then the upper extremities, and ultimately the entire torso; acquired skills are lost and muscle tone decreases. Tremors of the fingers and involuntary muscle contractions of the tongue occur. At a later stage, difficulty in the functioning of the respiratory system occurs. The course of the disease is not rapid, as with the congenital form; some children can live into adolescence. The prognosis of the disease depends on the degree of damage to the muscles responsible for the respiratory process.
3. Third form, late. The first symptoms appear after 2 years. By this time, the baby has already developed physically and psychologically according to age standards. The progression of the disease occurs slowly, gradually, and is characterized by lethargy and clumsiness of the child when walking and other motor processes. Paresis of the limbs develops, extinction of the swallowing and tendon reflex, signs of bulbar palsy, as well as deformation of bone tissue. The third form is milder than the first two, patients can live up to 30 years.

There are forms of spinal muscular amyotrophy that manifest themselves at a later age.

1. Kuldberg-Welander disease It is considered the mildest form of childhood atrophy. In most cases, the onset of the disease occurs during adolescence, but there are also earlier manifestations.

There are cases where patients do not lose the ability to walk and care for themselves, living a long life.

1. Kennedy's disease associated with a gene mutation on the X chromosome, transmitted to girls from two parents, to boys from their mother. Appears in adulthood.

The malignant course of the congenital Werdnig-Hoffmann form gives little chance for planning the future of such children, however, with forms 2 and 3, it is possible to prolong the child’s life; it is important to respond in time to infectious diseases that sharply worsen the patient’s condition and lead to the appearance of new symptoms, the worst of which - respiratory dysfunction.

External manifestations of Werdnig-Hoffman disease

What is the danger of the disease?

Due to the fact that Werdnig-Hoffmann disease is incurable, the most important danger is death. With the congenital form, children live for a fairly short period of time, the disease progresses quickly and leaves no chance of survival.

With the help of modern research, it is possible to detect the presence of a disease in the fetus during pregnancy and prevent the birth of a seriously ill child.

In other forms, the disease shows its first signs after an intestinal or respiratory infection; subsequently, parents, under the guidance of attending physicians, limit the possibility of the child developing an infection, which will aggravate its course and pose a mortal danger. However, bronchitis, pneumonia and other diseases of the ENT organs are often found in patients with Werdnig-Hoffmann disease.

Diagnosis and treatment of Werdnig-Hofmann disease

In the early stages of the disease, it can be difficult to differentiate the disease, since the symptoms may be similar to other diseases:

1. acute poliomyelitis is characterized by the absence of disease progression and asymmetrical paralysis;
2. myopathy – also of hereditary origin, has a progressive course, but the cause of muscle weakness is a violation of metabolic processes in them;
3. congenital myatonia is most similar to Werdnig-Hoffmann disease; they can be distinguished quite easily using a biopsy of muscle tissue.

To diagnose the disease, a neurologist will need data on the first manifestation of symptoms, the nature of their development, and the presence of concomitant diseases.

A number of studies are carried out to make a diagnosis:

1. Electroneuromyography reveals disturbances in the functioning of the neuromuscular system. Changes in the muscle type are observed, which indicates pathology of the motor neutron;
2. Genetic analysis reveals a mutation in the SMN gene;
3. Blood biochemistry for the level of creatine kinase, indicators within the normal range do not exclude the disease;
4. Muscle biopsy for morphological examination, which reveals fascicular atrophy of muscle fibers alternating with healthy ones, as well as proliferation of connective tissue;
5. MRI to rule out other diseases.

To diagnose the fetus in utero, chorionic villus biopsy, cordocentesis, and amniocentesis are used. Detection of the disease is an indication for termination of pregnancy. It is impossible to cure a patient with Werdnig-Hoffman disease. To prolong life and improve its quality, symptomatic treatment is used. The development of the disease and the worsening of symptoms are restrained by ensuring the functioning of metabolic processes in muscle tissue.

With the help of physical therapy and massage, blood circulation is improved, the risk of congestion is reduced, muscle performance is maintained, and joint immobility and loss of elasticity are prevented. Loads should be short and careful. Physiotherapy helps to maintain motor skills at the existing level and strengthen them. Special devices will help you move independently, use a computer, and even write. Portable ventilators enable patients to stay outside the hospital and live their lives more productively.

Prognosis of Werdnig-Hoffman disease

The prognosis for this disease is quite unfavorable. There is no chance of recovery. The only way to prolong life is timely treatment, healthy eating and reasonable exercise. Children with congenital Werdnig-Hoffmann form die within 6 months - 2 years. Later onset of the disease gives more time to live.