This disease occurs in early childhood and is characterized by a malignant course with rapid progression. Depending on the time of the appearance of the first symptoms and the rate of growth of the process, three forms of the disease are distinguished: congenital, early childhood and late.
congenital form can manifest itself in the intrauterine period. In such cases, fetal movement, which was normal at first, becomes weak in late pregnancy, childbirth can be pathological, and already in the first days after the birth of a child, obvious muscle paresis is detected with a decrease in muscle tone and a decrease in tendon reflexes. Sometimes complete areflexia is stated. There may be early bulbar symptoms, manifested by a weak cry, sluggish sucking. In a child, fibrillation in the tongue, a decrease in the pharyngeal reflex, and hypomia can be detected. Tachycardia is usually noted. Often the disease is combined with a number of malformations, mental retardation. The course of the disease is very rapid, death occurs by 1-l.5 years.
early childhood form characterized by a slightly milder course compared to congenital. This form is considered classical. The onset of the disease refers to the age of 1.5 years. In most cases, the first symptoms are detected after some kind of infection or food intoxication. The child, who had previously developed more or less normally, quickly loses the previously acquired motor skills, stops walking, standing or sitting. Flaccid paresis first occurs in the legs, then in the muscles of the trunk and arms. The condition deteriorates relatively quickly, weakness appears in the muscles of the neck, bulbar muscles. By the age of 4-5, usually as a result of respiratory failure, pneumonia develops and death occurs. In patients, flaccid paresis is accompanied by the development of tendon contractures. General hyperhidrosis is often noted.
late form begins after the age of 1.5-2 years and flows easily compared to the first two forms. Patients up to 10 years old can retain the ability to move.
The leading symptoms are paresis in the proximal parts of the legs, then the arms. Muscle atrophy is difficult to detect due to a well-defined subcutaneous fat layer. Tendon reflexes fade early. A small tremor of the fingers of outstretched hands (fascicular tremor) is characteristic. Typical bone deformities, especially in the chest, as well as in the lower extremities. Bulbar symptoms are represented by atrophy of the muscles of the tongue with fibrillar twitches, paresis of the soft palate with a decrease in the pharyngeal reflex.
A special variant of Verdnig-Hoffmann spinal atrophy is known - progressive bulbar paralysis or Fazio-Londe disease. The disease often begins by the end of the second year of life, sometimes at juvenile age, is characterized by weakness in the muscles of the face, including chewing muscles, difficulty swallowing, voice changes, atrophy in the muscles of the tongue. Ophthalmoplegia may be seen. The disease progresses rapidly, death occurs after 6-12 months from the onset of the first symptoms. Bulbar disorders can be accompanied by flaccid paresis and paralysis of the extremities, sometimes they do not have time to develop, however, at autopsy, damage to the cells of the anterior horns of the spinal cord is constantly stated throughout. Familial cases of Fazio-Londe disease are described, when the bottom and more siblings suffered. The type of hereditary transmission is autosomal recessive.
Diagnosis of spinal amyotrophy of Werdnig-Hoffmann is based (in addition to the early onset of the disease and the characteristic clinical picture) on the results of additional research methods, of which, first of all, electromyography should be indicated. Almost always, spontaneous bioelectrical activity at rest with the presence of fasciculation potentials is detected. With arbitrary contractions, a reduced electrical activity with a “palisade rhythm” is recorded, which indicates synchronization phenomena and an increase in the duration of the potential.
Pathological examination reveals a decrease in the number of cells in the anterior horns of the spinal cord, degenerative changes in them. Pathological changes are especially pronounced in the region of the lumbar and cervical thickenings, as well as in the motor nuclei of the cranial nerves. Changes are revealed in the anterior roots, in the intramuscular sections of the nerve endings. In the latter there is a disappearance of normal terminals, their excessive branching.
In biochemical studies, changes in carbohydrate metabolism are found. So, E. A. Savelyeva-Vasilyeva (1973) found that glycolysis in patients with spinal Werdnig-Hoffmann amyotrophy approaches the embryonic type. Quite often, significant disturbances in creatine-creatinine metabolism are found - an increase in urinary creatine excretion, a decrease in creatinine excretion. It is important to note that the level of enzymes in the blood serum almost does not change.
Spinal amyotrophy of Werdnig-Hoffmann refers to hereditary diseases with an autosomal recessive type of transmission. The primary biochemical defect is unknown. There is an assumption that a genetic defect leads to defective laying of the cells of the anterior horns of the spinal cord, to a violation of their differentiation and to a possible underdevelopment of muscle cholinergic receptors.
When establishing the diagnosis of spinal Werdnig-Hoffmann amyotrophy, differentiation is carried out with Oppenheim myotonia. According to most researchers, Oppenheim's myotopia is not an independent nosological entity, but a syndrome, the leading manifestation of which is pronounced muscle hypotension. In this regard, the term "floppy baby" or "sluggish child" is now widely used. The “flaccid child” syndrome is observed in diseases such as congenital muscular dystrophy, a benign form of congenital hypotension, rickets, an atonic form of cerebral palsy, as well as in transverse spinal cord injury, intrauterine acute poliomyelitis, or polyradiculoneuritis. The “flaccid child” syndrome can occur with universal muscle hypoplasia (Krabbe disease), with glycogenosis, in particular with type II - or Pompe disease (universal glycogenosis).
Treatment with spinal amyotrophy of Werdnig-Hoffmann, it is reduced to the appointment of massage and exercise therapy, which should be carried out systematically. Radical treatment is not available.
Some improvement is provided by drugs such as cerebrolysin, aminalon, anticholinesterase agents (prozerin, oksazil, galantamine, sanguinarine), B vitamins. stages of the disease.

Pseudomyopathic form of progressive spinal Kugelberg-Welander amyotrophy

In 1942, Wohlfart first described a disease manifested by muscular atrophy and paresis and resembling primary muscular dystrophy, but with widespread fasciculations. In 1956, Kugelberg and Welander emphasized that such a disease proceeds relatively benignly; careful electromyographic control allowed the authors to clarify the neurogenic nature of muscle atrophy and classify the latter as a spinal lesion.
The disease begins in most cases at the age of 3-6 years and progresses very slowly. Described cases and later onset of the first symptoms, including in adults. Patients for a long time retain the possibility of self-service and even sometimes working capacity. According to clinical symptoms, the disease resembles a limb-girdle form (Erb muscular dystrophy). Muscle weakness and atrophy develop first in the proximal lower extremities and pelvic girdle, then spread to the shoulder girdle. The similarity with Erb's myodystrophy is reinforced by the presence of a significant number of cases of pseudohypertrophy of the gastrocnemius muscles. Bone deformities and tendon retractions are usually absent. With Kugelberg-Welander amyotrophy, the process can spread to the bulbar region, which is clinically manifested by slight hypotrophy of the tongue, fibrillar twitches. The latter can also be observed in the muscles of the face. Movement disorders, as manifestations of nuclear damage to the X-IX-XII and VII pairs of cranial nerves, are detected very late, only at an advanced stage of the pathological process.
Additional studies with Kugelberg-Welander spinal amyotrophy reveal rather peculiar changes - electromyography indicates distinct signs of spinal damage, at the same time, the pathomorphological picture during muscle biopsy is represented by a mixed nature of the pathology - along with neurogenic amyotrophy, there are indications of some dystrophic signs. Similar data are obtained in biochemical studies - the activity of enzymes, including creatine phosphokinase, is often increased, although to a lesser extent than with true myopathy. Changes in creatine-creatinine metabolism.
Spinal Kugelberg-Welander amyotrophy refers to hereditary diseases with an autosomal recessive type of transmission and, apparently, with incomplete penetrance, since sporadic cases are very frequent. There are separate descriptions with autosomal dominant inheritance of the disease. Until now, not all authors consider Kugelberg-Velandeoa amyotrophy as an independent disease, considering it only a "mild" variant of Werdnig-Hoffmann disease. The main argument in favor of such a statement is the observation in one family of sibs with both forms of spinal amyotrophy. However, the presence of such symptoms as muscle pseudohypertrophy, hyperfermentemia, and a special mildness of the course testifies in favor of the nosological independence of Kugelberg-Welander amyotrophy. From a practical point of view, this is important, since there is a different prognosis for the two forms of spinal amyotrophy.
There is no specific treatment for Kugelberg-Welander amyotrophy. Symptomatic and restorative agents are used. The right choice of profession, the elimination of physical overload is important.

Neurogenic humeroscapular-facial syndrome (spinal variant of Landouzi-Dejerine myopathy)

In a number of cases, with spinal amyotrophy, the localization of atrophies is typical for Landouzy-Dejerine myodystrophy, i.e., it mainly concerns the muscles of the shoulder girdle, especially the fixing shoulder blades, the proximal sections of the upper limbs (biceps and triceps muscles of the shoulder) and facial muscles. An electromyographic study reveals a high-amplitude, reduced bioelectrical activity with clear fasciculation potentials, i.e., a picture characteristic of the spinal level of the lesion. The activity of enzymes in the blood serum of such patients is usually normal, the indicators of creatine-creatinine metabolism are almost unchanged. At present, many descriptions of such cases have accumulated in the literature, and a number of authors distinguish neurogenic muscular atrophy, reminiscent of the Landouzy-Dejerine form.
The onset of the disease, as with Landouzy-Dejerine myodystrophy, at different ages - both in childhood and in adults (from 7 to 40 years). The disease proceeds relatively favorably, progression is slow. In the spinal variant of the Landouzy-Dejerine disease, the asymmetry of the lesion is more clearly revealed. Relatively often there are changes in the heart, documented by ECG anomalies, in contrast to myodystrophy of the humeroscapular-facial. Facial muscle involvement may be minimal or be detected late.
The scapular-peroneal form of amyotrophy is considered by some authors as a kind of neurogenic variant of Landouzi-Dejerine myodystrophy. In these cases, involvement in the pathological process of the heart is sometimes described.

Rare forms of spinal muscular atrophy

Hereditary distal muscular atrophy is a rare form of spinal amyotrophy. The disease begins with the distal parts of the lower extremities, the distal parts of the hands are gradually involved in the process, generalization of the process can be observed.
A neurogenic form of oculopharyngeal atrophy transmitted in an autosomal dominant manner has been described. The authors reported a case where autopsy revealed degeneration of the cells of the anterior horns of the spinal cord and the motor nuclei of the cranial nerves, including the nuclei of III and X pairs.
Spinal amyotrophies include most cases of multiple congenital arthrogrypposis. The pathological process consists in the underdevelopment of the cells of the anterior horns of the spinal cord with paresis of the corresponding muscles. As a result of the occurrence of uneven muscle traction, contractures and abnormal development of the joints can form in utero. In a biopsy and EMG study, in some cases, neurogenic and myogenic changes are noted, in connection with which the term "pseudomyopathy" has been proposed.
There are also undifferentiated forms of spinal amyotrophy with rapidly progressive, slowly progressive and non-progressive course.

spinal muscular atrophy

Edited by pediatrician Tatyana Nikolaevna Shevko.

Description

Other names

Werdnig-Hoffmann disease, Kugelberg-Welander disease, SMA, motor neuron disease

Diagnosis codes

ICD-10

G12.0, type I spinal muscular atrophy; Werdnig-Hoffmann disease

G12.1, other hereditary spinal muscular atrophies

G12.9, spinal muscular atrophy, unspecified

For more information on disease codes, seeICD-10 for spinal muscular atrophies and related syndromes .

Description

Spinal muscular atrophy (SMA) is an autosomal recessive disorder that causes reduced survival of the cells in the anterior horns of the spinal cord (lower motor neurons) that innervate voluntary muscles. This leads to progressive muscle atrophy and weakness. As more information about SMA is uncovered, it is becoming clear that motor neurons are not the only part of the body affected by this disease, and that SMA may actually be a multisystem disease. Traditionally, SMA has been classified by age of onset and severity. Classification by maximal motor function (the patient cannot sit, the patient can sit, the patient can walk) may give a clearer picture of the clinical treatment needs of such patients than traditional classifications. Children with type I SMA are never able to sit up on their own. Children with type II can sit but cannot walk, and patients with type III can walk independently, although only for a short time.

Prevalence

SMA is one of the most common recessive diseases (only cystic fibrosis is more common) and is present in about 1 in 6,000 newborns. It is estimated that 1 in 40 people carry the gene that causes SMA type I. SMA type I is the leading cause of infant death due to hereditary diseases.

Genetics

SMA is caused by the absence or defect of a protein that ensures the survival of motor neurons (SMN protein). This protein is encoded by the geneSMN1,located on the long arm of chromosome 5. In most cases of SMA, there is a deletion of exon 7 and (or) exon 8 (in various combinations).SMN2is a pseudogene similar toSMN1but not functional.SMN2also located on the long arm of chromosome 5 (5q) and may have multiple copies. Gene copy numberSMN2, probably affects the severity of SMA through a complex mechanism that ensures the production of motor neuron survival protein in a certain amount by the defective genomeSMN2. The SMN protein complex is apparently involved in the biogenesis of specific ribonucleoproteins that regulate gene transcription.

Forecasts

The prognosis varies and depends on the subtype of SMA. Most children with type I SMA die in early infancy if they do not receive assisted ventilation. Families of children with type I SMA are increasingly choosing mechanical ventilation (both invasive and non-invasive) as supportive care. Such ventilation can increase life expectancy, but most children with type I SMA die from respiratory failure due to infection before the end of the second year of life. Patients with type II and III SMA may have a normal life expectancy, but their options are severely limited and they experience respiratory and other complications. Preventive therapies that focus on breathing, nutrition, and orthopedics can help increase life expectancy. Although Cochrane studies have not found statistically effective treatments for SMA types I, II, and III, treatments that target genetic mechanisms offer renewed hope that, over time, there will be approved treatments have been developed.

Roles of Medical Home (outpatient treatment under the supervision of specialists)

Ideally, care for children with SMA should be provided in a multidisciplinary clinic. If it is not possible to provide care in such a clinic, it is extremely important that medical care is provided in the Medical Home mode (outpatient treatment under the supervision of specialists). This will help families organize specialized care, tracking of functional changes, ongoing management of acute illnesses, and lifelong support for the child. Children with SMA should be monitored for respiratory function (during wakefulness and during sleep), gastrointestinal function and nutritional balance, musculoskeletal status, oral hygiene, and independent and family activities.

Practical guide

The standard of care guidance (listed below) is the consensus opinion of experts, however, these recommendations have not been supported by the results of properly conducted clinical trials. It is expected that the standards of care will be updated in the near future to reflect the new information that becomes available as more research is being done.

Clinical Assessment

Review

Physicians should suspect SMA in infants and children with proximal muscle weakness (shoulder and pelvic girdle) and absent or very weak tendon reflexes. Infants from the earliest stages of the disease may have difficulty breathing (eg, a bell-shaped chest, mild coughing or crying) and trouble feeding.

Screening

family members

Siblings of a patient with SMA have a 1:4 chance of having the disease at birth and a 2:4 chance of being carriers of SMA. An analysis for carriage is carried out in adults, as well as brothers or sisters of the patient over the age of 18 years. Although the need for analysis in at-risk younger siblings who do not show symptoms of SMA is controversial, many experts believe that early detection of SMA in children can lead to improved clinical outcomes. Therefore, such tests are recommended if the family so desires. The American College of Medical Genetics endorses the practice of offering all couples planning or in early pregnancy a genetic test.SMN1.

Painting

The presentation of the disease and clinical characteristics differ depending on the subtype of SMA.

• SMA type I (Werdnig-Hoffmann disease) ) appears in newborns. Such children will not be able to learn to sit or walk, they experience difficulties with breathing and swallowing, including the control of oral secretions, their life expectancy is significantly reduced. Other symptoms are inability to hold the head, bell-shaped chest, weak crying and coughing, tongue atrophy and fasciculation (twitching) of the tongue, and paradoxical breathing
• SMA type IImanifests later in the first year of life or during the first 2 years of life. Usually such children can sit, but not walk. From the initial stages of the disease, small tremor-like movements of the hands and fingers are observed. As weakness progresses, children often have trouble breathing and swallowing, including difficulty gaining weight due to bulbar muscle weakness, weak cough, and nocturnal hypoventilation. Difficulties with swallowing and opening the jaw wide have been shown to lead to malnutrition. Virtually all children with this condition develop joint contractures and scoliosis over time. Therefore, proactive intervention is required.
• SMA type III (Kugelberg-Welander disease) has a much more variable form early in development than types I and II, but usually presents in childhood or early adolescence. Such children can sit and walk (although some of them may lose this ability over time). As with type II SMA, children with type III SMA may experience fine tremor-like movements of the hands and fingers. Atrophy of the quadriceps muscle may be pronounced. Children with SMA type III may have fewer breathing and swallowing problems than children with SMA types I and II. Older children have scoliosis, contractures, and joint pain.
• SMA type 0appears before birth. In such cases, for a period of about 30 weeks, reduced fetal mobility is detected. Newborns have severe hypotension, as well as congenital contractures, swallowing problems, and respiratory failure.
• SMA type IVmanifests itself in adults and will not be discussed further here.

Diagnostic criteria

The diagnosis is based on the results of a genetic analysis for a total deletion of exon 7 of the geneSMN1in children with relevant clinical symptoms. This assay is inexpensive and readily available; Laboratories where such analysis can be carried out can be found here:SMA analysis (GeneTests) or Analysis for SMA (Registry of Genetic Tests) .

Gene copy number determinationSMN2aids in prediction and is now becoming a standard part of genetic analysis for SMA. While most patients have a total deletion of exon 7, approximately 5% of children with SMA are genetically negative due to a deletion on one allele and a point mutation on the other. In such cases, clinical suspicion and electromyography (EMG) play an important role.

Differential Diagnosis

• SMA is usually easily diagnosed by clinical symptoms and confirmed by genetic testing. Differential diagnoses for a child who develops progressive muscle weakness are described below.
  
  Botulism in childhood occurs in children under the age of 12 months. Symptoms begin with constipation in a child who has not previously had problems with stool, and is accompanied by a weakening of facial expressions (expressive facial movements), problems with swallowing, weak crying and decreased mobility. As the disease progresses, it manifests itself more acutely than SMA. The diagnosis is made on the basis of clinical symptoms and detection of the presence of botulinum toxin in the child's stool.
  
  neuropathycover a wide range of syndromes with different dynamics. As a rule, sensory nerves are affected. Evidence of a predisposition to such diseases can often be found in a family history (for example, Charcot-Marie-Tooth disease or hereditary motor and sensory neuropathy). Acquired neuropathies, such as Guillain-Barré syndrome, develop rapidly - over a period of several days to one week. They rarely occur in children under 2 years of age. Diagnosis is confirmed by EMG and/or tests showing elevated levels of protein in the cerebrospinal fluid (CSF).

metabolic myopathy (eg, mitochondrial myopathy, Pompe disease) is much less common than SMA, but early clinical manifestations may be similar. Children with Pompe disease have severe, progressive cardiac dysfunction that is not characteristic of SMA.

Duchenne muscular dystrophy occurs only in boys. In this disease, there is an increase in the calf muscles, an extremely high level of creatine kinase (CK), and developmental delay is often present. Diagnosis is based on genetic tests for gene mutationsDMD(dystrophin gene).

X-linked SMA and SMA with respiratory distress (SMARD) may be similar in clinical symptoms to SMA, but these diseases have a different genetic etiology. SMARD1 appears as distal (rather than proximal) muscle weakness. In this case, there is a deformity of the foot, as well as respiratory failure, which often comes on suddenly. This disease is caused by mutations in the geneIGMBP2, localized on the long arm of the 11th chromosome 11q13.3, encoding protein 2, microbinding immunoglobulins. Children with X-linked SMA may have a family history of inheriting X-linked diseases, and these children are tested forSMN1will be negative. More and more new genes are associated with these phenotypes, and in case of any suspicion, it is recommended to contact a highly specialized clinic for examination.

congenital myopathy manifests itself in the form of non-progressive weakness. It is diagnosed on the basis of a muscle biopsy.

Possible measures against respiratory failure

Children with type I SMA are susceptible to respiratory failure due to infection or aspiration (foreign body in the airways). To avoid emergencies, this possibility should be discussed with the patient's family as soon as possible, as well as preventive measures (for example, non-invasive ventilation of the lungs, the CoughAssist device (a device that clears the airways by simulating a real cough), the use of a gastrostomy tube). Frequent pneumonia or respiratory disease may indicate impending respiratory failure or aspiration.

History and examination

Early detection of weakness is critical to the initial evaluation. In young children, the diagnosis of muscle weakness can be difficult, but close attention to functionality allows for a more or less accurate assessment. On the Children's Muscle Disease Organization website, you can find videos of children with normal and weak muscles. Such materials can be helpful in identifying mild weakness.

Family history

SMA is an autosomal recessive disorder that usually occurs in people with no family history of it; however, health care providers should inquire about family history and consanguinity of child and infant mortality.

History of pregnancy or perinatal history

Despite the absence of specific problems in the history of pregnancy, sometimes mothers of children with SMA type I report a decrease in fetal mobility in late pregnancy. Babies with type 0 and type I SMA may have arthrogryposis and feeding difficulties at birth, and may have a bell-shaped chest.

Tracking the current state and anamnesis

From the gastrointestinal tract / nutrition: is weight gain sufficient? Ask questions about gastrointestinal problems such as reflux, stomach pain, and constipation. Children with neuromuscular diseases, including SMA, suffer from osteopenia. Are you getting enough calcium and vitamin D? Are there fractures?

From the respiratory system: ask questions about children's breathing problems while awake, including while eating. Inquire about history of pneumonia, intensity of cough, presence of reactive airway disease, recent lung function tests (oximetry), use of ventilators (non-invasive ventilatory support devices such as CPAP). ) and BiPAP (biphasic positive airway pressure ventilator), as well as night or continuous ventilators) and using the CoughAssist device. Also ask questions about sleep, previous sleep studies, snoring indicative of obstructive sleep apnea and hypoventilation, frequency of nocturnal awakenings, daytime sleepiness, and morning headaches. Check your immunization history, including pneumococcal and influenza vaccines.

Swallowing problems:ask questions about coughing and choking while eating and drinking (especially thin liquids) and the intensity of the cough. Ask if the patient has a suction machine at home.

From the musculoskeletal system: Ask questions about recent changes in muscle strength, fatigue, and functionality. Ask about how comfortable the wheelchair, assisted getting up and other equipment are to use and how they are maintained. Ask if the family has a special license plate or sign for people with disabilities.

Orthopedics: Ask questions about orthotic use, joint pain, range of motion, and history of fractures.

Comprehensive examination (head, eyes, ears, nose and throat): ask questions about chronic ear infections.

Dentistry: Take a dental history and inquire about the ability to open and close the jaw.

Development and training

Early stages of motor development, such as the ability to hold one's head, are often delayed. Lying on their back, children can remain in the classic “frog” position. There will be no delay in the development of speech and language skills. Developmental test results indicate a significant delay in gross motor skills, but cognitive skills develop normally. The study of the daily functioning of the body, for example,Pediatric Disability Assessment (PEDI) (for a fee), can help assess the dynamics of the development of the functional capabilities of the child. Often such an examination is suggested by the child's doctor. Ideally, the results of such examinations should be reported in Medical Home materials. Families must sign an authorization to release information in order to obtain such information in their hands or bring a copy of such materials to a doctor's appointment. Accounting for changes in the functional capabilities of the child will allow a more accurate assessment of the development of the disease.

Functioning in society and family

Ask questions about the child's family and community support, access to needed resources, and any other social issues related to the child and family. Are the necessary conditions created in the school? Is there someone left with the child when the parents are away? Does a child with SMA have difficulty breathing without the use of assistive devices or when using BiPAP, how does this affect the family, what is the opinion of family members on the next steps? Has the possibility of an acute respiratory illness been considered, and has an action plan been drawn up in this case?

Physical examination

General

Infants with SMA are often active and attuned to interacting with objects around them, children with SMA are often capable and quite sociable.

Vital Signs

Children with weakened respiratory muscles may have an increased respiratory rate and heart rate.

Characteristics of physical development

Weight, height, body mass index: Due to nutritional problems, infants with SMA may be underweight or overweight (especially when using a gastrostomy tube for feeding). Close attention to patterns of nutrition and physical development is very important. Given the reduced muscle mass, it may be ideal when the weight is relatively low in relation to height. Growth charts for normal children are not applicable in such cases.

Leather

Are there signs of destruction of the skin, cooling of the extremities, are there spots on the skin, is there a yeast infection (on the tongue, in depressions on the body)?

Comprehensive examination (head, eyes, ears, nose and throat) )

Check the ability to open the jaw, as well as the size of the tonsils.

Mouth/Teeth

Check for bad breath, dental caries, and drooling that could be caused by swallowing problems.

Rib cage

The chest wall may be bell-shaped. Listen to the lungs and make observations to check for breathing problems. Check the respiratory rate and the presence of paradoxical movements of the chest and abdominal wall. If possible, watch your child cough or cry. Review the results of control oximetry, peak flow measurements, and forced vital capacity measurements. Measure the circumference of the chest along the line of the nipple and track its growth. The circumference of the chest and head should be approximately equal in the first year of life. If the chest is not growing, there is an increased risk of the child developing respiratory failure.

Abdomen

Non-soft moving masses may represent hard, "stagnant" stools.

Limbs/musculoskeletal system

Check if joint contractures are progressing. Conduct an examination to assess muscle strength and functionality. Sensitivity must be fully preserved. Check for clinical scoliosis and hip dislocation.

Neurological examination

Check tone, proximal muscle strength and reflexes. The central nervous system should function normally.

Analyzes and checks

Sensory testing

Vision and hearing tests should be performed at the appropriate age.

Lab tests

Regular tests are not required. Laboratory results should be reviewed for malnutrition, carnitine deficiency, hypercalcemia, and iron deficiency anemia. Urinalysis will detect urinary tract infection, etc. Against the background of the disease, it is necessary to check for acidosis or electrolyte imbalance. As a rule, the level of creatinine is low. Often, an increase in the level of CK (creatine kinase) is observed in patients suffering from muscle diseases such as Duchenne muscular dystrophy; however, the level of CK content can also be increased in patients with SMA in the stage of active denervation.

Visualization

If the child takes a long time to eat, is slowly gaining weight, or has trouble swallowing, and to identify cases of aspiration, perform a visual examination using a video of the swallowing process. Due to the fact that such a study is carried out in the presence of a speech therapist, strategies for safer feeding (for example, thickening of liquids) can be developed. Chest x-ray can help diagnose chronic aspiration or acute pneumonia; X-ray of the spine and pelvic bones can diagnose scoliosis or hip dislocation.

Genetic analysis

Definitive diagnosis should be based on molecular genetic analysis for gene mutationSMN1and number of copiesSMN2. The results of such an analysis are usually ready in a few weeks. A small percentage of children with SMA will test negative for a total exon 7 deletion, but after a more detailed analysis, it turns out that the child has SMA with a mutation not detected by standard genetic analysis.

Other tests and examinations

Other possible tests and examinations:

• Electromyography (EMG) results may indicate the possibility of SMA. In this case, genetic analysis should be performed.
• For various reasons, some doctors perform muscle biopsies. However, after a biopsy performed in SMA, genetic testing should be performed to allow for a definitive diagnosis.
• To assess the state of the respiratory system, if necessary, lung function tests and sleep studies are carried out.
• To assess the condition of underweight or overweight children, it is advisable to conduct research on child nutrition.
• If the child has had fractures repeatedly, and also as part of the initial examination in cases where the child has been immobile for a long time and has been in a wheelchair, especially if he has taken valproic acid or proton pump inhibitors, a DERA scan (dual energy X-ray absorptiometry) is performed.

For examination and monitoring of the patient's condition, it is preferable to use the services of a clinic specializing in SMA in children, provided that such a clinic is available to the patient. Depending on the location of the patient, the additional involvement of subspecialists such as physiotherapists and rehabilitation and pulmonologists may be beneficial.

Comprehensive care for children with SMA and other neuromuscular disorders is often available at clinics sponsored by the Muscular Dystrophy Association. Together with primary care professionals, staff at these clinics can coordinate preventive care and referrals to subspecialists.

Children's genetics

Genetic testing and genetic counseling can be done at clinics that specialize in SMA or other neuromuscular disorders. If it is not possible to use the services of such clinics on a regular basis, an initial visit to conduct genetic tests and discuss their results, as well as periodic visits to resolve emerging problems, may be useful.

Pediatric pulmonology

Referral to a pediatric pulmonologist is especially important for children with type 0 and type I SMA, as they are at risk of developing respiratory failure. Often the first problems arise with ventilation of the lungs at night; deterioration may not be noticeable. In the early stages of SMA development, consultations with pulmonologists are recommended even for children with SMA, whose lungs are in normal condition.

Pediatric gastroenterology

Seeing pediatric gastroenterologists can be helpful in assessing and managing eating and feeding problems. Consideration should also be given to such specialists if swallowing problems, reflux, constipation, or failure to gain sufficient weight are experienced.

Children's orthopedics

Most children with any type of SMA will benefit from periodic referral to a pediatric orthopedic specialist to assess for and manage musculoskeletal complications. If a child with SMA has congenital arthrogryposis, early consultation with such specialists is critical.

Specialists in pediatric physiotherapy and rehabilitation will help optimize the child's motor function and daily activities. Typically, this includes physical therapy as well as rehabilitation and speech therapy.

Pediatric otolaryngology

If a child develops obstructive sleep apnea, referral to a pediatric otolaryngologist should be considered.

Treatment and observation

Different approaches to solving common problems in children with spinal muscular atrophy

Physical development or weight gain

Standard growth charts are often not applicable to children with SMA. Children with SMA whose physical development follows the growth curves of "normal" children may be functionally obese or at risk of developing insulin resistance and metabolic syndrome complications. Muscle atrophy makes it difficult to solve nutritional problems; close observation is very important. Children with type I SMA develop dysphagia early, and a gastrostomy tube and a Nissen fundoplication are often used early to prevent aspiration and pneumonia.

Development (cognitive, motor, speech, socio-emotional)

The cognitive and emotional development of children with SMA is normal. Although speech is normal from a neurological point of view, communication, especially with patients with type I SMA, can be difficult due to the weakness of the body. Children may need adaptive devices to facilitate communication.

Viral infections

Due to respiratory muscle weakness and a weak cough, children with SMA are at risk of developing serious upper respiratory tract infections. Family members should be advised to take appropriate precautions (thorough handwashing and limiting interaction with sick people). Patients are required to have an annual influenza vaccination; in infants with type I SMA, RSV (respiratory syncytial virus) prophylaxis may be given.

Bacterial infections

Children with SMA are at risk of developing bacterial pneumonia as a primary consequence or complication of a viral upper respiratory tract infection or aspiration. It is recommended that pneumococcal vaccination is appropriate for the age of the child. Necessary preventive measures are the use of non-invasive ventilation of the lungs and the CoughAssist device in the early stages.

Expectant management when visiting the hospital leads to better outcomes

Expectant management includes increased attention to nutrition and respiratory status before and after surgery, as well as during urgent hospital visits for exacerbations. Temporary use of a nasogastric or nasojejunal tube, or peripheral or total parenteral nutrition may be helpful.

Written care plans make emergency care easier

Visiting emergency rooms is quite difficult for families of children with SMA, as well as with any other complex disease, because. Families need to describe in detail their history of the disease and their preference for child care, as well as the reason for seeking care. Action plans should be drawn up in case of respiratory failure and such plans should be reviewed during non-urgent home visits. In order for the family's decision to resuscitate to be passed on to other physicians, families should be provided with appropriate documentation.

Early postoperative stimulation of ambulation helps maintain muscle strength

The requirement to remain still after major surgery (for example, to correct scoliosis or hip dislocation) can lead to loss of the ability to move. Under these conditions, early recovery of the ability to move can be of great help in maintaining muscle strength.

Systems

Neurology

The clinical course of SMA is unstable and difficult to predict. Proactive management of complications improves quality of life and increases life expectancy. Although there are currently no drugs that cure SMA definitively, there are currently several clinical studies in this direction.

Working with narrow specialists and using other resources

Clinics specializing in muscular dystrophy

There are a fairly large number of clinics of the Muscular Dystrophy Association (MDA) in the United States and Canada. These clinics specialize in helping people with neuromuscular disorders. Visiting such a clinic is free for the patient. These clinics may also conduct clinical trials.

Pediatric neurology

In areas without specialized clinics, pediatric neurologists with experience in neuromuscular disorders should be responsible for monitoring children with SMA.

Respiratory system

Patients who are unable to sit up on their own, and sometimes patients who are able to sit, may have serious breathing problems. A bell-shaped chest or paradoxical breathing may indicate that the respiratory muscles (with the exception of the diaphragm) are weakened. Swallowing problems and chronic aspiration aggravate the situation. The weakening of the cough complicates the cleaning of the respiratory tract from the secret. An aggravating factor in respiratory problems is scoliosis.

Patients able and unable to sit should be consulted by a pulmonologist as soon as possible after diagnosis. General recommendations for the provision of respiratory support for patients with SMA type I and many patients with SMA type II include airway clearance techniques such as the use of the CoughAssist machine and nighttime non-invasive ventilation such as the BiPAP machine.

A sleep study should be performed to detect obstructive sleep apnea and central hypoventilation. These problems may occur before the child has obvious daytime problems. In the event that the vital capacity is less than 40% of the expected value, it usually becomes necessary to use the BiPAP machine at night. The BiPAP device can also be used during the daytime when there is an urgent need for it, for example, in case of a respiratory disease or after surgery. In chapterCPAP and Bilevel PAP machines The Medical Home Portal website provides additional information on the indications for use of these devices and subsequent care.

Optimal preventive treatment includes optimizing nutrition, especially in surgical interventions and diseases. Some children can be taught the methods of "accumulative" breathing and incentive spirometry. As a rule, such training is carried out by specialists in pulmonology clinics. "Cumulative" breathing is a repetition of the following actions: inhalation and air retention. Children who are losing lung capacity will benefit from daily activities, but it is difficult to ensure the regularity of such activities.

If the child has a weakened cough, percussion and postural drainage should be performed; Secretion removal is also aided by the use of the CoughAssist apparatus. Removal of secretions from the respiratory tract should be carried out, if necessary, under the guidance of an ENT specialist. For children whose secretion is difficult to remove, drug treatment to reduce secretion, injections of botulinum toxin, and ligation of the salivary gland ducts can be used. Swallowing problems are optimally addressed, for example, by thickening fluids and using gastrostomy tubes; in the presence of reflux, a Nissen fundoplication may be useful.

Make sure you get immunizations, especially pneumococcal vaccine and annual flu vaccine. In patients unable to sit, and most patients who are able to sit, RSV prophylaxis should be given. Respiratory infections and symptoms of reactive airway disease should be treated early and intensively. If hospitalization is required for acute severe respiratory illness, non-invasive ventilation should be considered; children with SMA often have difficulty turning off the ventilator. Supplemental oxygen without mechanical ventilation should be used with caution as this can lead to a decrease in the activity of the respiratory center, which will cause hypercarbia and atelectasis.

Working with narrow specialists and using other resources

Pediatric pulmonology

Most children with SMA will need follow-up with a pulmonologist in parallel with the provision of outpatient care (Medical Home). With such children, you should contact a specialist for diagnosis, as well as periodically visit a specialist for follow-up.

Diagnostics and therapy of sleep disorders in children

Children with SMA may need ventilators during sleep before they have problems while awake; a specialist should be consulted to assess the child's sleep and take appropriate measures, if necessary.

Pediatric otolaryngology

If salivation, problems with swallowing, or sleep apnea should consider the need to see a specialist.

Nutrition/Growth/Bone Condition

If food is taken orally, malnutrition may occur. Risk factors are fatigue, frequent choking or coughing during meals, the need for a very large amount of time for eating. Standard weight charts are not applicable due to the loss of muscle mass that occurs despite supplementation. Measurements of body mass index, weight-for-height ratio, and a triceps skinfold test are often included as part of a nutritional assessment. Such measurements can be useful in determining nutrient reserves. If the child has repeatedly had fractures, the intake should be maximized.calcium and vitamin D and also consider taking bisphosphonates.

Poor weight gain is often observed, which is often associated with a decrease in food intake and an increase in energy expenditure for breathing. If an infant is significantly underweight, a professional nutritionist should be consulted. To increase the intake of calories in the body, a method can be usedPower Packing (increasing the calorie content of food without increasing its volume) , food pureeing or gastrostomy tubes (both as a complete replacement for oral food intake, and in addition to it). Although the decision to use a gastrostomy tube is difficult to make, excessive feeding times for infants with SMA who are unable to sit can make it difficult to manage their care. Families may start with a nasogastric tube before deciding to use a gastrostomy tube. For basic information about the different types of feeding tubes and an overview of Medical Home's role in feeding tube care, see .

Patients who are able to sit as well as patients who are able to walk may also experience excessive weight gain, which can make mobility very difficult; Preventing excess weight gain is easier than losing excess weight. At the first sign of a tendency to overweight, it is necessary to contact nutritionists.

Working with narrow specialists and using other resources

Nutrition/diet

For children with SMA who are underweight or overweight, it may be helpful to see a doctor.

Pediatric endocrinology

If a child has low bone mineral density on a DERA scan and has had repeated fractures, a referral to a pediatric endocrinologist should be considered.

Musculoskeletal system

For musculoskeletal problems, including joint contractures, hip dislocations, and scoliosis, prevention and ongoing monitoring should begin from the time of diagnosis. Contact should be made with early childhood intervention services, physiotherapy, physiatry and orthopedics, depending on the decision of the family and the availability of experienced professionals in the community.

Upright positioning devices are prescribed to support lung function, gastrointestinal function, and provide developmental assistance to patients unable to sit. Patients who are able to sit and patients who are unable to sit should use equipment to assist in getting up. To achieve positive results, such equipment must be used for 1-2 hours a day. This provides support for the function of the lungs, the gastrointestinal tract, reduces the risk of fractures, and delays the development of scoliosis and contractures. Orthopedic devices and walking equipment should be used even if walking and other activities are not a practical goal. All children with SMA are encouraged to use mobility scooters, wheelchairs (both manual and powered), or other devices, as needed, to enable them to participate in social activities appropriate for the child's age. In order to avoid the development of contractures, a set of motor exercises should be performed daily, and in postoperative periods, it is necessary to resume activities associated with weight loading as soon as possible.

Scoliosis develops in more than half of children with SMA, and many of these children will need surgery. The optimal time for the operation depends on the state of the respiratory system, the physical development of the child and the degree of curvature of the spine. Sometimes a corset is used to delay surgery as long as possible and gain time for linear growth before fusion; however, the corset may adversely affect respiratory function and should be used with caution, especially in very debilitated children. Observations of respiratory function should be carried out regularly; surgery to correct scoliosis should be performed before serious problems arise with respiratory function. The operation should be performed when the scoliosis angle reaches approximately 40 degrees, or immediately before. The operation entails a number of problems: blood loss, difficulties in turning off the artificial lung ventilation device in the child and a long period of rehabilitation.

Hip subluxation and dislocation are common problems in patients unable to sit, patients able to sit, and sometimes patients able to walk. Once a year or every 2 years, a hip x-ray should be performed. Sitting with a dislocated hip becomes even more difficult, and the dislocation can negatively affect an already impaired respiratory function and cause chronic pain. The risks and benefits of hip subluxation surgery should be carefully weighed by family members in consultation with an experienced orthopedic surgeon. When considering surgery for a patient who is able to walk, it should be borne in mind that immobility for a certain period of time after surgery can lead to contractures or changes in functional walking skills.

Working with narrow specialists and using other resources

Children's orthopedics

It is necessary to contact a specialist in pediatric orthopedics as soon as possible to identify hip dislocation, scoliosis and joint contractures, as well as their treatment; Ideally, a specialist in this field should have experience working with children with SMA.

Hospitals

Orthopedic care is provided to children with SMA at Shriners hospitals. A map of the location of hospitals can be found in the sectionShriners Hospitals for Children .

Pediatric Physiotherapy and Rehabilitation

Pediatric physiotherapy and rehabilitation specialists should be consulted to optimize functional abilities, including the ability to perform daily activities and move around.

Physical therapy

Physical therapy should be considered as early as possible to increase the child's range of motion, strengthen their musculature, consider the use of mobility aids, and prevent contractures.

Early Childhood Intervention Programs

Early childhood intervention programs and community programs typically offer different types of therapy to young children (physiotherapy, rehabilitation, speech therapy, etc.).

Nose/throat/oral cavity/swallowing

Swallowing problems often occur in patients unable to sit and those who are able to. Such problems can lead to aspiration of oral secretions and food, bad breath, dental caries, and drooling. Patient nutritionists (this could be rehabilitation or speech therapy) should optimize how these patients are fed. If children have trouble chewing and swallowing food, pureeing foods may be helpful. In cases where children are coughing, choking, silent aspiration of thin liquids, or have problems with the lungs associated with aspiration, it is necessary to thicken the liquids with a substance such as Simply Thick or Thick It (see sectionThickening liquids and pureeing foods ). In addition, especially patients unable to sit and patients able to sit, a feeding tube, nasogastric tube, nasojejunal tube or gastrostomy tube may be required. Note that while a gastrostomy tube may provide enough calories to the body, it does not prevent mouth secretions from being aspirated into the airways. Additional clinical information on this subject can be found in the sectionFeeding tubes and gastrostomy .

Working with narrow specialists and using other resources

Pediatric gastroenterology

If the child is underweight, has aspiration, or has trouble swallowing, a pediatric gastroenterology specialist should be considered. Use of a gastrostomy tube may be helpful.

General Pediatric Surgery

A pediatric surgeon should be consulted if a gastrostomy tube is needed, especially if a fundoplication is being considered.

The functioning of the gastrointestinal tract and intestines

Gastrointestinal problems such as reflux, delayed gastric emptying, and constipation are fairly common. For information about medicines that may be helpful in your treatment, seeGastroesophageal reflux (general information) . A Nissen fundoplication may be required to protect the airways of patients unable to sit, especially those with oral eating and aspiration disorders. Constipation must be treated intensively, because. they can lead to discomfort, aggravate the problem with gastric emptying, reduce appetite and cause reflux. See sectionTreatment of constipation (general information) .

Working with narrow specialists and using other resources

Pediatric gastroenterology

If a child is not responding to standard treatment, a pediatric gastroenterologist should be considered.

General Pediatric Surgery

Depending on the availability of experienced specialists in the community, it may be necessary to refer to a pediatric general surgeon if a child needs a gastrostomy tube.

Developmental Pediatrics

Depending on the availability of experienced professionals in the community, referral to developmental pediatrics specialists can be helpful in addressing constipation at the behavioral and medical levels.

Dentistry

Contractures make it difficult for many children with SMA to open their mouth wide. This often leads to problems with eating and complicates oral care. Children with SMA should be treated by a pediatric dentist as soon as possible. If a child with SMA requires surgery for other reasons, such as placement of a gastrostomy tube, consideration should be given to combining oral cleaning, fissure sealant, and dental filling with such surgery. If sedation is required for such procedures, the clinician should be aware of the high risk associated with this, due to the breathing problems in children with SMA.

Working with narrow specialists and using other resources

Children's dentistry

General dentistry for children

Dentists on this list, with relevant experience, have expressed their willingness to treat children with special treatment needs.

Recreation and leisure

Children with SMA should be able to participate in recreational activities. One of the fastest growing types of such activities in the United States is adaptive sports. Toys and games can be changed according to the capabilities of the child; for older children with SMA, alternative ways of learning to drive can be considered. On our portal page Modifications there is information on how to adapt toys for a child. In chapterRecreational activities you can find ideas for organizing such events. In chapter Game (Cure SMA) advice is given on which Play and Heal sets with toys can be used. These recommendations are given by other families of children with SMA based on their personal experience.

Working with narrow specialists and using other resources

Entertainment programs/events

Funding and availability of specialist assistance

Families may have difficulty accessing the resources they need, but organizations such as Cure SMA . Because Resources vary slightly from state to state, families should contact their local Divisions for People with Disabilities or similar state agencies for information. Muscular Dystrophy Association (MDA) clinics operate in many cities across the country and are an excellent resource for children and adults with SMA. These clinic appointments are sponsored by the MDA and provide partial financial support for consultation visits and purchase of wheelchairs. See section . Families should inquire about Supplemental Security Income (SSI) opportunities directly with government agencies or by working with early childhood education and intervention program coordinators. For other helpful ideas, seeFinancing medical care for your child at .

Family

Families should be encouraged to work with support organizations such as Cure SMA and Muscular Dystrophy Association , through which they can connect with other families with children with SMA. If the child is between 2.5 and 18 years old, families should also be advised to contactWish Fulfillment Organizations such as Dream Factory, Make a Wish Foundation and Starlight Foundation.

There are many options for providing appropriate care for a child with SMA, and families can benefit greatly from open discussion of alternatives in these areas. Some families will choose to forego diagnostic and therapeutic interventions they consider invasive, while others will opt for intensive interventions that may prolong a patient's life. All carers should understand the family's preferences in these matters. Repeated discussions are most effective in a calm environment, rather than in an emergency situation, such as when a child needs urgent intubation due to pneumonia. Prevention, such as early use of non-invasive ventilation, can help avoid crises. The decision to intensively treat SMA can be changed at any time. In cases where families refuse intensive intervention, children's hospice services should be offered to them.A Guide for Families on Joint Determination of the Standard of Care for SMA (ICC) ( 267 KB) can help families learn about health care options for their children.

Working with narrow specialists and using other resources

Hospice and palliative care

If necessary, hospices with experience in caring for children should be used.

Wish Fulfillment Funds

You can apply to such funds if the child is from 2.5 to 18 years old.

Children's genetics

Families may benefit from periodically contacting child geneticists to review current and emerging issues (eg, advances in genetic research, options for prenatal and preimplantation diagnosis for family planning, and risks to siblings of a child with SMA).

FAQ

What are the early signs of SMA?

Signs and symptoms differ depending on the age of the patient and the subtype of SMA. Typically, children with SMA experience hypotension, proximal weakness (weakness in the shoulders and pelvis), feeding problems, and/or complications related to insufficient breathing. Early signs of weakness include:

• Abdominal breathing or use of accessory muscles
• The person conducting the examination feels that the child seems to "slip out of the hands" when he is held under the armpits
• The child cannot voluntarily bend the neck when lying on its back, or the head is thrown back when the child is sitting down
• Difficulty getting up from the floor (including the Gowers maneuver, both complete and modified)

A video depicting relevant signs when examining children with frailty at an early age, including patients with SMA, can be found in the sectionOrganization of childhood muscle diseases .

What are the most important issues to focus on during regular doctor visits to ensure care for patients with SMA?

Regular preventive assessment of sitting ability, joint range of motion, nutritional capacity, as well as assessment of weight and respiratory status can improve the quality and length of life of a child with SMA. It is also critical to ask questions about family and community support and access to resources that may affect the care a child with SMA receives.

What impact does SMA have on a child's development, including physical development?

Children with SMA are at risk for nutritional deficiencies and underweight. Patients unable to sit are especially likely to be underweight due to reduced food intake and increased energy expenditure for breathing. Standard weight charts are not applicable due to the loss of muscle mass that occurs despite supplementation. Children with SMA whose physical development follows the growth curves of "normal" children may be functionally obese or at risk for the complications of metabolic syndrome.

Spinal Werdnig-Hoffman amyotrophy is a hereditary pathology of the nerves that affects the part of them that controls the skeletal muscles. It is characterized by weakness of all the muscles in the body at once. More than half of the nerve cells that control muscles are located in the spinal cord. That is why the disease is called "spinal". It is also called “muscular” because of the detrimental effect on the muscles: they do not receive any signals from these same nerves. "Atrophy" is a medical term that refers to the wasting or shrinking of what is not being used. Here it refers to inactive muscles. A person with such a disease has no way to sit, move, or even take care of himself. It is impossible to cure it. By conducting prenatal diagnosis, you can prevent the birth of a baby with this disease. Here we will talk about how this pathology is inherited, what are its manifestations, and also about how you can help a sick person.

Spinal Werdnig-Hoffmann amyotrophy is named after the two scientists who first described it. In the second half of the 19th century, they proved the morphological essence of the disease. At first, both scientists believed that this pathology had only one form. But already in the 20th century, scientists Kukelberg and Welander discovered its other clinical form, with a genetic cause similar to that discovered by Werdnig and Hoffmann. Several clinical forms of spinal amyotrophy are now known. They are united by a common hereditary defect.

This pathology is hereditary. It is based on a mutation on the fifth chromosome. Mutates the gene that synthesizes the SMN protein. This protein is necessary for motor neurons to develop exactly as they should. Should the fifth chromosome mutate, and this will negatively affect motor neurons, preventing their development, or even completely destroying them. As a result, the muscle cannot receive control signals from the nerves, and therefore cannot function. It turns out that not a single movement associated with it is performed.

The mutated gene has an autosomal recessive mode of inheritance. The phrase is deciphered as follows: for the development of spinal amyotrophy, it is necessary that both parents have a mutant gene. Simply put, the disease will not develop if at least one of the parents was not a carrier of the mutated gene. At the same time, they themselves do not get sick: people have paired genes, and the healthy gene dominates in the father and mother of the child. In this case, a sick baby is born in about a quarter of cases. Scientists estimate that about 2% of living people are carriers of the gene with this mutation.

Classification

Three types of this pathology are known.

1. The most severe, manifesting itself before the others.
2. Medium.
3. The easiest, manifested at a very late age.

According to some doctors, there is another variety: moderate/mild SMA, which appears already in an adult.

It is worth noting that in addition to spinal Werdnig-Hoffman amyotrophy, there are other types of SMA that differ in symptoms and types of inheritance. They are listed in the table below.

Table number 1. Types of SMA.

CMA name	Inheritance type	Features and symptoms
SMAX1	X-linked recessive	It is observed mainly in the elderly, affects the bulbar nerves of the skull, causes descending paralysis.
SMAX2	X - clutch recessive	Congenital aggressive form, leading to death up to 3 months. Causes weakness, areflexia, contractures and fractures.
SMAX3	X - clutch recessive	It affects mainly boys. Atrophy of all distal muscles. Slow progression of symptoms.
Distal DCMA1	Autosomal recessive	Congenital, mainly the hands are affected, more severe respiratory disorders are possible.
Distal forms DCMA2 - DCMA5	Autosomal recessive	All four forms are characterized by slow progression, DCMA5 is diagnosed in young people.
Juvenile SMA (type HMN1)	autosomal dominant	Occurs in youth
congenital spinal atrophy	autosomal dominant	Violation of innervation and atrophy of the hips, feet, knees with contracture and deformity; sometimes the vocal cords are affected.
SMA Finkel	autosomal dominant	It begins mainly at the age of 35-37, but cases of the disease have also been recorded in childhood. Slowly develops first in the legs and then in the arms. Activity and reflexes are reduced, involuntary trembling (fasciculation) is observed.
SMA (type LED1)	autosomal dominant	Atrophy of the lower extremities in newborns.
CMA with congenital bone fractures	autosomal recessive	The symptoms are more severe, as about the disease. Verdnig-Hoffman, burdened with fractures.
CMA with hypoplasia	autosomal dominant	Congenital brain anomaly with cerebral symptoms, microcephaly and developmental delay.

Symptoms of pathology

The congenital type of the disease (SMA I) begins to appear before the baby is six months old. Prior to this, such a child may move sluggishly. It is not so rare that spinal amyotrophy in a baby can be noticed even at the very beginning of the postembryonic period of his life - his deep reflexes fade away:

• the baby's cry is not loud enough;
• he has difficulty suckling;
• he can't hold his head.

It is possible to determine such a pathology in an infant from the first days of life.

If this becomes noticeable later, which rarely happens, the baby can learn to hold his head, or even sit, but pathology quickly reduces such skills to zero. The following is also typical:

• early speech problems;
• deterioration of the pharyngeal reflex;
• fascicular twitching of the tongue.

This type of pathology can be attached to oligophrenia, as well as pathologies of skeletal development:

• deformities of the chest (funnel-shaped / keeled form);
• curvature of the spine (scoliosis);
• articular contractures.

Other congenital diseases are not uncommon. For example:

• hemangiomas;
• hydrocephalus;
• clubfoot;
• hip dysplasia;
• cryptorchidism.

SMA I the most "harmful": it is accompanied by developing paralysis, as well as paresis of the muscles responsible for breathing. Because of the latter, respiratory failure develops, due to which the patient may even die. A violation of swallowing can be the cause of food entering the respiratory tract and the development of aspiration pneumonia. It can also lead to death.

SMA II begins to appear after the baby is six months old. At this age, the baby is already satisfactorily developed, he can stand, hold his head, sit down, roll over. However, almost never a sick baby has time to master the skills of walking. In most cases, this disease manifests itself after the baby suffers any acute infectious pathology. For example, food poisoning.

When SMA II only begins to manifest itself, the baby has peripheral paresis in the legs, which then quickly appear in the arms, in the trunk. Diffuse muscle hypotonia appears, deep reflexes begin to disappear. You can also notice the following:

• tendon contractures;
• tremor of fingers;
• fasciculations (involuntary twitching) of the tongue.

Important! Later, bulbar syndrome begins to appear, respiratory failure develops. Due to the slow development of this type of SMA compared to the congenital form, the affected individual usually lives to the age of fifteen.

SMA III, it is Kugelberg-Welander amyotrophy - the least harmful type of spinal amyotrophy. It begins to appear when the child is two years old. Sometimes it can be asymptomatic even up to 30 years. However, in this case, the patient is no longer a child, which, however, does not make him healthier. With SMA III, the development of the psyche is not delayed, the patient can move for a long time without assistance. He even has a chance to be able to take care of himself even in extreme old age.

SMA IV, which is also an adult form of spinal amyotrophy, is a slowly developing pathology. It usually starts after the person is 35 years old. This form, if it shortens life, is insignificant. On the other hand, the patient has the following picture:

• weak proximal muscles;
• fasciculations;
• deterioration of tendon reflexes;
• loss of the ability to walk.

The electromyogram shows "palisade rhythm" - spontaneous rhythmic activity. So you can identify the pathology of the anterior spinal horns. If we conduct a morphological study of muscle biopsy specimens, one can notice atro- and hypertrophied fibers of the first and second types. Small round fibers also accumulate, which are interspersed with hypertrophied fibers - this is a "bundle" atrophy. If a pathomorphological study is carried out, swelling / wrinkling / atrophy of the motor neurons of the spinal anterior horns becomes noticeable, and quite often also the nuclei of the nerves that exit the brain.

How is this pathology diagnosed?

To make a correct diagnosis, the neurologist must have information about the age at which the first symptoms appeared in a person, how quickly they progress. He also needs to find out neurological data. Moreover, the most important thing here is information about whether the patient has peripheral movement disorders along with full preservation of sensitivity. It is also important for a neurologist to find out if the patient has congenital abnormalities, bone deformity. Werdnig-Hoffman amyotrophy can also be diagnosed by a neonatologist. With the help of a differential technique, it is possible to diagnose:

• myopathy;
• developing Duchenne muscular dystrophy;
• amyotrophic lateral sclerosis;
• syringomyelia;
• polio;
• sluggish child syndrome;
• metabolic pathologies.

To confirm the results of the diagnosis, do electroneuromyography. This is the name of the examination of the neuromuscular apparatus. It allows you to detect the changes needed to exclude the primary muscular type of the disease, as well as to verify the presence of motor neuron disease. A biochemical blood test is too small to detect any serious increase in the level of creatine phosphinase, which occurs during the development of muscle dystrophy. An MRI/CT of the spine can occasionally detect atrophy of the anterior horns of the spinal cord, but this technique can be used to make sure that there is no other spinal disease.

The diagnosis of Werdnig-Hoffmann amyotrophy is finally made only when muscle biopsy data and DNA analysis are obtained. With the help of a morphological examination of a muscle biopsy, it is possible to identify pathognomonic fascicular atrophy of muscles, alternating with zones of atrophy of myofibrils and healthy tissue, individual hypertrophied myofibrils, as well as places of connective growths. Mandatory genetic studies include direct and indirect diagnostics. The direct method makes it possible to identify the heterozygous carriage of a gene aberration, and this is necessary for genetic counseling of relatives of patients, as well as spouses planning the birth of a child. In all this, the quantitative study of the genes of the SMA locus is important.

By conducting a prenatal genetic examination, you can reduce the risk of having a baby suffering from Werdnig-Hoffman amyotrophy. To obtain the genetic material of the fetus, invasive methods for diagnosing the fetus should be used:

• amniocentesis;
• chorion biopsy;
• cordocentesis.

Having found Werdnig-Hoffman amyotrophy in the fetus, the question of abortion should be raised.

Differential method of diagnosing the disease

According to the symptoms, this pathology can be confused with congenital myopathy. This is bad muscle tone. A biopsy is used to rule out muscle hypotension. Acute poliomyelitis is similar to Werdnig-Hoffman spinal amyotrophy. This pathology has a stormy onset, accompanied by a sharply elevated body temperature and multiple asymmetric paralysis. After a few days, the acute phase of poliomyelitis turns into a recovery phase. With glycogenosis, as well as congenital myopathies, muscle tone also decreases.

But these pathologies differ from spinal amyotrophy in that they are provoked not by gene mutations, but by the following factors:

• metabolic problems;
• carcinoma;
• hormonal disorder.

At the same time, the following should also be excluded:

• Gaucher disease;
• Down syndrome;
• botulism.

How is this pathology treated, as well as how to predict its further course

Today, there is no etiopathogenetic treatment of spinal amyotrophy. Now she is being treated by improving the metabolism in the peripheral nervous system as well as in the muscles, just to delay the development of symptoms.

In this case, in different combinations, the means of the following groups are used:

• neurometabolites - drugs produced from the hydrolyzate of porcine brains, gamma-aminobutyric acid, as well as piracetam;
• agents that facilitate the transmission of impulses to the muscles - galantamine, sanguinarine, neostigmine, ipidacrine;
• medicines that improve the trophism of myofibrils - coenzyme Q10, L-carnitine, Cerebrolysin, Cytoflavin, Glutamic acid, ATP, Carnitine chloride, Methionine, Potassium orotate, Tocopherol acetate;
• vitamins B - Milgamma, Neurovitan, Kombilipen;
• anabolics - Retabolil, Nerobol;
• drugs to improve the conduction of impulses between nerves and muscles - Prozerin, Neuromidin, Dibazol, Galantamine;
• medicines in order to improve blood circulation - nicotinic acid, scopolamine.

In addition, with spinal amyotrophy, it is useful to do exercise therapy, as well as conduct gentle massage sessions.

Today's technologies are of great help to make life easier for patients and their loved ones. Portable ventilators, as well as automated wheelchairs, help them with this. To improve the mobility of patients, there are various methods of orthopedic correction. But the main prospects for the treatment of SMA lie in the constantly evolving genetics, as well as in the search for opportunities to use genetic engineering to correct genetic diseases.

Anesthesia

If a person, regardless of age, requires surgery, certain precautions must be followed. The entire surgical team must be aware of what constitutes SMA. Most of all it concerns the anesthesiologist.

At the beginning of the development of this pathology in muscle cells that do not receive nerve signals, anomalies sometimes occur due to the attempts of the muscles to “reach out” to the nerves associated with them. Because of such anomalies, muscle relaxants, often used in surgery, can be dangerous. Having an idea about such problems, you can choose safe drugs.

Diet for spinal amyotrophy

At this point, no diet has yet been confirmed to be beneficial for SMA.

According to a large number of parents, a diet that includes a lot of protein or special food supplements can increase the strength of the child's muscles. But, despite the obvious need for good nutrition for a sick child, it has not yet been proven that he needs a particular diet. Moreover, some products can even harm his body.

For example, the amino acid menu is sometimes fraught with even greater problems for those children who have too little muscle tissue in their bodies. According to some experts, with a lack of muscle tissue, it cannot properly process amino acids and then their level in the blood rises too much.

Some children benefit from eating small amounts, more than three or four times a day. You just need to divide for the patient the entire amount of food taken by a healthy peer of the patient per day into several parts.

Among patients with SMA there are overweight people. It is possible that the reason for this lies in a too high-calorie diet, coupled with a lack of movement. If possible, the patient should, with the help of a doctor and a nutritionist, bring his weight back to normal. This is important not only for health and appearance, but also for those who care for such a patient. After all, they help the patient to rise and move every day.

Important! There are doctors who advise taking over-the-counter nutritional supplements. For example, creatine, coenzyme Q10. Research is currently underway on how creatine works in this pathology.

exercise therapy

According to most doctors, comfortable physical activity, if only not to go to extremes, is very beneficial for the well-being and health of the SMA patient.

Joints need to be able to move and not be at risk of injury. At the same time, the range of motion should be maintained in order to keep the joints elastic. At the same time, blood circulation must be maintained. Also, what is most important for children is to keep mobility high in order to explore the environment.

Important! It is best to conduct classes in a pool filled with water having a temperature of 30-32 degrees Celsius. But, firstly, a person with SMA should not swim himself, and secondly, certain safety measures must be observed.

According to some doctors, it is not so necessary to pay a lot of attention to the gradual decrease in the already insufficient number of motor neurons in the body. Research is needed to determine whether this should be taken into account when developing a complex of exercise therapy. The opinions of professionals differ: some believe that it is impossible to overload the body with exercises, while others believe that by doing the gymnastic complex “before you turn blue”, you can force the death of the remaining motor neurons. So, with exercise therapy, accuracy is required and gymnastics must be stopped without bringing yourself to exhaustion.

Occupational and physical therapy programs are useful for people of all ages who want to learn how to make the most of their remaining muscle function, as well as learn how to best cope with everyday tasks.

Now you can find devices that are useful even for kids - for exploring the surrounding space. Little children can be helped by everything that the human genius has come up with to solve this problem, from walkers to orthoses.

Moreover, there are families who independently invent and manufacture their own devices, equipped with special functions. For example, those in which you can change the height so that the child can at least crawl on the floor, even sit on the table.

A person of any age, if he has SMA, significantly benefits from adaptations for solving everyday tasks that do not cause difficulties in healthy people.

The way to prevent this pathology

To prevent Werdnig-Hoffmann amyotrophy in a newborn, parents should undergo a diagnosis of genetic abnormalities in time, and also, while carrying a child, the expectant mother should also conduct a pretonal DNA diagnosis of the baby. If the Werdnig-Hoffman amyotrophy is detected, the question of abortion arises.

How to predict the development of pathology

Now the spinal amyotrophy of Werdnig-Hoffman is incurable. Forecasts are absolutely unfavorable. If this occurs in a baby in the first days after his birth, he usually dies before he is six months old. If symptoms begin to appear after three months of age, the average age of such a child is a couple of years. The maximum age to which such a patient can live is eight years. The early childhood type of this pathology progresses much more slowly, and such a child lives to adolescence - fourteen to fifteen years.

Yet current technology may allow sick children to live much longer. Thanks to the ventilation of the lungs with the help of modern portable devices, as well as feeding with a tube that delivers food directly to the stomach, a small person can live for many more years.

Video - The genetic basis of spinal muscular atrophy

Other diseases - clinics in Moscow

Choose among the best clinics by reviews and the best price and make an appointment

Other diseases - specialists in Moscow

Choose among the best specialists by reviews and the best price and make an appointment

These are genetic diseases that manifest as muscle atrophy and are caused by degenerative changes in the spinal motor neurons and motor nuclei of the brain stem. A common symptom complex is symmetrical flaccid paralysis with muscle atrophy and fasciculations against the background of an intact sensory sphere. Spinal amyotrophies are diagnosed according to family history, neurological status, EPS of the neuromuscular apparatus, MRI of the spine, DNA analysis, and morphological examination of muscle biopsy. Treatment is ineffective. The prognosis depends on the form of spinal muscular atrophy and the age of its onset.

General information

Spinal amyotrophies (spinal muscular atrophy, SMA) are hereditary diseases, which are based on the degeneration of motor neurons of the spinal cord and brain stem. Described at the end of the 19th century. Their frequency is 1 case per 6-10 thousand newborns. About 85% of spinal muscular atrophies are proximal forms with more pronounced weakness and atrophy of the proximal muscle groups of the limbs. The distal forms account for only 10% of SMA. Today, spinal amyotrophies are of practical interest for a number of disciplines: pediatric and adult neurology, pediatrics, and genetics.

Causes

Thanks to modern genetics, it has been established that the emerging degenerative processes of motor neurons are caused by mutations in the SMN, NAIP, H4F5, BTF2p44 genes located on the 5th chromosome at the 5q13 locus. Despite the fact that spinal amyotrophies are determined by aberrations of one chromosomal locus, they represent a group of heterogeneous nosologies, some of which appear in infancy, while others manifest in adults. In most cases, amyotrophies are inherited in an autosomal recessive manner.

Classification

It is generally accepted to divide spinal muscular atrophies into children's and adults. Children's SMA are classified into early (debuting in the first months of life), later and juvenile. Children's spinal amyotrophies are represented by:

• juvenile form of Kugelberg-Welander;
• chronic infantile SMA;
• Vialetto-van Lare syndrome (bulbospinal form with deafness);
• Fazio-Londe syndrome.

Adult forms of SMA manifest between the ages of 16 and 60 and are characterized by a more benign clinical course. Adult SMAs include:

• scapuloperoneal;
• face-shoulder and oculopharyngeal forms;
• distal MCA;
• monomelic SMA.

There are also isolated and combined spinal amyotrophies. Isolated SMA are characterized by a predominance of spinal motor neuron involvement, which in many cases is the only manifestation of the disease. Combined spinal amyotrophies are rare clinical forms in which the symptom complex of amyotrophy is combined with another neurological or somatic pathology. Combinations of SMA with congenital heart defects, deafness, oligophrenia, pontocerebellar hypoplasia, and congenital fractures have been described.

Symptoms of spinal amyotrophies

Common to spinal muscular atrophies is a symptom complex of symmetric flaccid peripheral paralysis: weakness, atrophy and hypotonia of the muscle groups of the same limbs (often both legs first, and then the arms) and trunk. Pyramidal disorders are not typical, but may develop in advanced stages. There are no sensory disturbances, the function of the pelvic organs is preserved. More pronounced damage to the proximal (with proximal SMA) or distal (with distal SMA) muscle groups draws attention. The presence of fascicular twitches and fibrillations is typical.

Werdnig-Hoffmann disease

It occurs in 3 clinical variants. The congenital variant debuts in the first 6 months. life and is the most malignant. Its symptoms can manifest themselves even in the prenatal period with a slight movement of the fetus. Children from birth have muscular hypotonia, they are not able to roll over and hold their heads, with a later debut they cannot sit. The frog posture is pathognomonic - the child lies with the limbs spread apart and bent at the knees and elbows.

Amyotrophies are ascending in nature - first they occur in the legs, then the arms are involved, later - the respiratory muscles, muscles of the pharynx and larynx. Accompanied by mental retardation. By 1.5 years, death occurs.

Early spinal amyotrophy manifests up to 1.5 years, often after an infectious disease. The child loses motor abilities, cannot stand or even sit. Peripheral paresis is combined with contractures. Once the respiratory muscles are involved, respiratory failure and congestive pneumonia develop. Death usually occurs before the age of 5 years. The late variant makes its debut after 1.5 years, and is distinguished by the preservation of motor ability up to 10 years of age. Lethal outcome occurs by 15-18 years.

Juvenile spinal Kugelberg-Welander amyotrophy

It is characterized by a debut in the period from 2 to 15 years. It starts with damage to the proximal muscles of the legs and the pelvic girdle, then captures the shoulder girdle. About a quarter of patients have pseudohypertrophy, which makes the clinic similar to the manifestations of Becker muscular dystrophy. In terms of differential diagnosis, the presence of muscle fasciculations and EMG data are of great importance. The course of Kugelberg-Welander amyotrophy is benign without bone deformities; for a number of years, patients remain capable of self-care.

Kennedy bulbospinal amyotrophy

It is inherited recessively linked to the X chromosome, manifests only in men after the age of 30. Typically slow, relatively benign course. Debuts with amyotrophy of proximal leg muscles. Bulbar disorders appear after 10-20 years and, due to slow progression, do not cause violations of vital functions. There may be a tremor of the head and hands. The pathognomonic symptom is fascicular twitching in the perioral muscles. Endocrine pathology is often noted: testicular atrophy, decreased libido, gynecomastia, diabetes mellitus.

Distal SMA Duchenne-Arana

It can have both recessive and dominant type of inheritance. The debut occurs more often at the age of 20, but can occur at any time up to 50 years. Amyotrophies begin in the hands and lead to the formation of a "clawed hand", then cover the forearm and shoulder, in connection with which the hand takes on the form of a "skeleton hand". Paresis of the muscles of the legs, thighs and torso join much later. Cases of manifestation of the disease by monoparesis (lesion of one hand) are described. The prognosis is favorable, except in cases where this type of SMA is combined with torsion dystonia and parkinsonism.

Scapulo-peroneal SMA of Vulpiana

It manifests itself in the period from 20 to 40 years with amyotrophies of the shoulder girdle. "Pterygoid vanes" are typical. Then the lesion of the peroneal muscle group (extensors of the foot and lower leg) joins. In some cases, the peroneal muscles are first affected, and then the shoulder girdle. Vulpian's spinal amyotrophy is characterized by a slow course with the preservation of the ability to move 30-40 years after its debut.

Diagnostics

In the neurological status of patients, flaccid para- or tetraparesis and muscle atrophy are determined with a predominant lesion of the proximal or distal muscles, a decrease or complete loss of tendon reflexes, the sensory sphere is not disturbed. Bulbar disorders, damage to the respiratory muscles can be detected. To determine the nature of a neuromuscular disease, an EFI of the neuromuscular apparatus is performed. EMG fixes the "palisade rhythm" typical for damage to the anterior horns of the spinal cord, ENG shows a decrease in the number of motor units and a decrease in the M-response.

Spinal amyotrophies are not always accompanied by changes on MRI of the spine, although in some cases atrophic changes in the anterior horns are visible on tomograms. A biochemical blood test with the determination of CPK, ALT and LDH does not reveal a significant increase in the level of these enzymes, which makes it possible to differentiate SMA from progressive muscular dystrophies. In order to clarify the diagnosis of "spinal amyotrophy", a muscle biopsy is performed. The study of biopsy specimens diagnoses "bundle atrophy" of myofibrils - the alternation of hypertrophied fibers with clusters of small atrophied fibers. The final verification of the diagnosis is possible with the help of genetics and DNA diagnostics.

In general, spinal amyotrophies have the following diagnostic criteria: hereditary nature, progressive course, the presence of fascicular contractions against the background of muscle atrophy, complete preservation of sensitivity, a picture of the pathology of the anterior horns according to EMG, detection of fascicular atrophy in the morphological analysis of muscle tissue. Differential diagnosis is carried out with muscular dystrophies, congenital myotonia, myopathies, cerebral palsy, ALS, Marfan's syndrome, chronic tick-borne encephalitis, poliomyelitis, atypical form of syringomyelia.

Treatment of spinal amyotrophies

Spinal amyotrophy is an indication for hospitalization during the initial diagnosis, deterioration of the patient's condition with the occurrence of respiratory disorders, the need for a second course of treatment (2 times a year). So far, there is no effective treatment for SMA. The therapy is aimed at stimulating the conduction of nerve impulses, enhancing peripheral circulation and maintaining energy metabolism in muscle tissue. Apply anticholinesterase pharmaceuticals (sanguinarine, ambenonium chloride, neostigmine); means that improve energy metabolism (coenzyme Q10, L-carnitine); vitamins gr. IN; drugs that simulate the work of the central nervous system (piracetam, gamma-aminobutyric acid).

In the US and Europe, neurologists use the drug riluzole for the treatment of ALS, but it has many side effects and low efficiency. Along with courses of drug treatment, massage and physiotherapy procedures are recommended for patients. The development of joint contractures and skeletal deformities is an indication for consulting an orthopedist with a decision on the use of special adaptive orthopedic structures.

Forecast

The prognosis depends entirely on the clinical variant of SMA and the age of its manifestation. Children's spinal amyotrophies have the most unfavorable prognosis; when they begin in infancy, they often lead to death during the first 2 years of a child's life. Spinal amyotrophies of adult age are distinguished by the ability of patients to independently serve themselves for many years, and with slow progression, they have a favorable prognosis not only for life, but also for the working capacity of patients (when creating optimal working conditions for them).

It is scary to know that the baby will never sit, stand, run. It is even more terrible to see how a normally growing and developing child suddenly begins to slowly fade away, constantly fall, after a few months he cannot climb the stairs, and one day he loses the ability to just stand up.

spinal muscular atrophy

Doctors group several types of hereditary disorders characterized by movement disorders into one group called spinal muscular atrophy. In the ICD-10, they go under the code G12 with additional indications of the type of disease.

According to researchers, about 0.01-0.02% of children are born with a diagnosis of SMA. The disease is more common in boys and men.

Spinal muscular atrophy is found mainly in children at an early age. However, some forms of the disease begin to appear only in adolescents or already adults. The insidiousness of pathology lies in the fact that it gradually, day by day, takes away from patients what they have managed to achieve.

For the first time, G. Werdnig described the pathology. He drew attention to the equilateral atrophy of the spinal cord, its anterior horns, peripheral nerve roots in 1891. The very next year, J. Hoffman was able to prove that it was an independent disease. In the middle of the XX century. researchers E. Kugelberg and L. Welander described a pathology that occurs at a later age and has a more favorable prognosis.

Symptoms

Each type of SMA has its own characteristics, but there are some symptoms that allow you to combine heterogeneous diseases into one group. This:

1. Increasing muscle weakness and atrophy.
2. With a disease that manifests itself after 1-2 years, degradation of already achieved abilities, for example, running, walking, is noticeable.
3. Tremor of the fingers. Trembling is also observed in the tongue.
4. Skeletal deformity.
5. Preservation of intellectual and mental health in most patients.

Types of SMA

Age, time of manifestation of symptoms, features of the course of pathology, prognosis allow us to distinguish several types of diseases.

This form of pathology is rarely described, it is often combined with the first type of SMA. The disease is congenital. It is characterized by a complete lack of movement, tendon reflexes, muscle weakness, limited movement of the knee joints. Respiratory disorders have been observed since birth.