Generality
Spinal muscular atrophy, or SMA, is a disease of the nervous system that affects the motor neurons causing a progressive weakening of the muscles of the body.
The SMA does not always present itself in the same way: in fact, there are more serious forms, which cause the patient's premature death, and less serious forms, with which one can live together.
For a correct diagnosis, genetic tests are needed, which analyze the chromosomal heritage of the individual under examination.
Unfortunately, spinal muscular atrophy does not heal; the only countermeasures available are to slow down the (inevitable) progression of the disease.
Brief reminder of genetics
Before describing spinal muscular atrophy, it is useful to make a brief reference to some key concepts.
What is DNA? It is the genetic heritage in which the physical features, predispositions, physical qualities, character, etc. are written. of a living organism. It is contained in all the cells of the body having a nucleus, as it is inside this one.
What are chromosomes? According to the definition, chromosomes are the structural units in which DNA is organized. The human cells contain, in their nucleus, 23 pairs of homologous chromosomes (22 of an autosomal non-sexual type and a couple of sexual type); each pair is different from another, as it has a specific gene sequence.
What are genes? They are short stretches, or sequences, of DNA with a fundamental biological meaning: from them, in fact, proteins are derived, that is, fundamental biological molecules for life. In genes, there is "written" part of what we are and what we will become.
What is a genetic mutation? It is an error within the DNA sequence that forms a gene. Because of this error, the resulting protein is defective or completely absent. In both cases, the effects can be deleterious both for the life of the cell, in which the mutation occurs, and for that of the organism in its totality. Congenital diseases and neoplasms (or tumors) are responsible for one or more genetic mutations.
What is spinal muscular atrophy?
Spinal muscular atrophy, also known as SMA, is a genetic disease that affects the motor neurons of the central nervous system (especially those of the spinal cord) causing the progressive loss of control of the muscles of the body.
There are more or less severe forms of SMA.
In severe patients, the simplest movements, such as walking or moving arms, respiratory function, standing and swallowing food are, at first, difficult and, then, completely impossible.
In less serious patients, however, only motor skills and standing are generally altered, so it is possible to live with the disease.
MOTONEURONI AND SMA
Figure: Spinal muscular atrophy is due to a deterioration of the motor neurons, located at the level of the spinal cord and exactly in correspondence of the ventral horns.
Motoneurons, or motor neurons, are cells that originate in the central nervous system (brain and spinal cord); they are used to conduct nerve signals that directly or indirectly control muscles and muscle movement. In fact, with their extensions (axons), the motor neurons reach the peripheral areas of the body. There are somatic motoneurons, which innervate the skeletal muscles directly, and visceral motor neurons, which indirectly innervate the glands, heart and smooth muscles.
The motor neurons of individuals affected by SMA gradually degenerate, causing an inactivated muscular atrophy and, in the most serious cases, paralysis, respiratory failure and death.
TYPES OF SMA
Based on the age of onset and severity of the disease, four forms of SMA have been recognized:
- Type I : is the most severe form; arises in children within the sixth month of life. Death occurs within the year of life.
- Type II : less severe form of I, affects children between 6 and 18 months of age. Patients generally die during adolescence or at the end of this.
- Type III : is less severe than type I and type II, appears around 3 years, but does not reduce the life expectancy of patients.
- Type IV : is the adult form of SMA; it does not cause the premature death of the sick and is, from the point of view of the symptoms, the least serious of the four.
Epidemiology
The incidence of SMA is equal to one case per 10, 000 people. There is no preference, on the part of the illness, for a particular sex; however, a form of SMA similar to type IV - the so-called Kennedy's disease (see the chapter on causes) - affects only male individuals.
Causes
SMA occurs due to a genetic mutation, which in most cases is transmitted from parents to children. The gene responsible for the disease is called SMN1 .
THE GENE SMN1 AND ITS MUTATION
Located on chromosome 5, the SMN1 gene produces a protein, called SMN, which is fundamental for the survival of motor neurons.
When SMN1 undergoes the mutation that causes SMA, SMN protein levels are drastically reduced, reaching a level of 10-20% of normal.
Figure: the hereditary transmission of an autosomal recessive disease. Sex does not affect, as the genetic mutation resides on a non-sexual (or autosomal) chromosome.
Faced with such low levels of SMN, the motor neurons begin to progressively degenerate, until, in the most serious cases, die.
The degeneration of the motor neurons involves a motor incapacity of the innervated muscles, consequently an atrophy from inactivity of the latter.
HOW IS THE MUTATION OF SMN1 ASSIGNED?
A disease transmitted from parents to children is a hereditary disease .
In order for SMA to be inherited by an individual, both parents must be carriers of the pathology (being a carrier does not necessarily mean being sick). When this condition is necessary, we speak of a recessive inherited genetic disease .
Two healthy carriers of the SMA have:
- 50% of the chances of giving birth to healthy children, like them
- 25% of the chances of giving birth to sick children of SMA
- 25% of the chances of giving birth to healthy children
According to a statistical survey, one person every 40-60 or so is a healthy carrier of the SMA.
ALTERNATIVE FORMS OF SMA: DIFFERENT CAUSES
During the various scientific studies related to SMA, it was observed that the same disorders, caused by spinal muscular atrophy, also arise for different reasons.
In fact, there are:
- Spinal muscular atrophy with respiratory distress ( SMARD ): the modes of transmission are the same as in traditional SMA. The only difference is the gene involved in the mutation, which is not SMN1, but IGHMBP2. The latter resides on chromosome 11.
- Bulbospinal muscular atrophy ( BSMA or Kennedy's disease ): the gene, affected by the mutation and responsible for the disease, is located on sex chromosome X. Individuals with BSMA are male only and inherit the chromosome with the mutation from the mother, who is a healthy carrier. It is considered a particular type of SMA type IV, because it occurs in adulthood.
Symptoms and Complications
To learn more: Symptoms Spinal Muscular Atrophy
Each type of SMA is characterized by specific symptoms and signs. Therefore, to state, in general, that spinal muscular atrophy alters movement and breathing capacity is limiting and not entirely correct.
A common aspect, however, exists: spinal muscular atrophy, of whatever form, does not alter the cognitive abilities of patients and does not cause any mental retardation.
TYPE I SMA
Type I SMA, which affects children within six months of birth, is the most common form of spinal muscular atrophy It is characterized by a severe degeneration of the motor neurons and the consequent weakening of the muscles; this causes problems in:
- Move and move
- Raise your head
- Stand in a sitting position
- Chew and ingest food
- To breathe
Typical signs of the disease are the limbs (upper and lower) that are thin and of soft consistency, due to the atrophy of the muscles.
Death occurs due to respiratory failure, generally within the first 12 months of life.
Some of the main sites of the atrophied muscles of SMA type I and II:
- Tongue and mouth in general
- Shoulders
- Lower and upper limbs
- Thoracic for breathing
- Neck
SMA TYPE II
The type II SMA symptomatology appears starting from the 6th -18th month of life and is getting worse over time. Death occurs during adolescence or at the end of this, due to respiratory failure.
Patients mainly manifest:
- Respiratory problems
- Arm and leg muscles spring
- Abnormal muscle contractions of the limbs
- Difficulty in ingesting food, due to the absence of a suitable musculature
- Deformation of hands and joints due to muscle weakness
It is possible that, over the years, a serious scoliosis develops.
SMA TYPE III
Type III SMA is a more moderate form of spinal muscular atrophy compared to type I and II.
It usually appears around the third year of life and follows a gradual deterioration. However, it does not cause the patient's premature death.
It causes problems with posture, hand tremors, difficulty walking, climbing stairs and running.
In the beginning, the disorders do not require supports for locomotion; subsequently, with the degeneration of the motor neurons, crutches and wheelchairs become fundamental.
Although it may happen, it is very rare that patients with type III SMA suffer from breathing problems and swallowing food.
SMA TYPE IV
Type IV SMA is the least common form of spinal muscular atrophy.
The characteristic symptoms and signs appear in adulthood, are moderate (although they worsen during old age) and consist of:
- Weakening of muscle tone, in the arms and legs
- Difficulty walking
- Sudden muscle tremors and contractions
Similarly to the SMA type III, one does not even die for the type IV SMA.
COMPLICATIONS
Complications arise in severe cases of SMA or in those situations not adequately treated.
They consist of:
- Choking from food, caused by reduced chewing and food ingestion.
- Ab ingestis pneumonia, caused by the entry or accumulation of foreign material (food, saliva or nasal secretions) in the lungs, which carries pathogenic bacteria.
- Paralysis and wheelchair . It usually occurs in cases of type II SMA.
- Malnutrition, due to difficulties in ingesting certain foods.
SPINAL MUSCULAR ATROPHY WITH RESPIRATORY DISTRESS (SMARD)
Figure: in red, the muscles of the body affected by spinal muscular atrophy are highlighted
Although caused by a different genetic mutation, the SMARD is very similar, for symptoms and signs, to type I SMA.
In fact, the muscles for breathing and locomotion are very weak, so much so that death occurs before the year of life.
BULBOSPINAL MUSCULAR ATROPHY (BSMA)
BSMA (or Kennedy's disease ) is a very rare form of muscular atrophy that affects, as has been said for a genetic reason, only male people.
The initial symptoms consist of hand tremors, cramps, abnormal muscle contractions and generalized muscle weakness. At an advanced stage, food ingestion problems may also arise due to atrophy of the muscles of the tongue and pulmonary infections (pneumonia).
In exceptional cases, Kennedy's disease can also cause unusual breast development (gynecomastia), diabetes and infertility.
In general, BSMA does not cause premature death of patients.
Diagnosis
The first suspicions of SMA may arise following an objective examination, in which the patient's disorders are evaluated, and after a dubious electromyography. However, for a certain diagnosis of the disease a genetic test is needed, through which the DNA of the person under examination is analyzed.
Regarding prenatal diagnosis, if you have valid reasons to fear an SMA, you can subject the fetus to specific genetic tests.
EXAMINATION OBJECTIVE
During the physical examination, the doctor, first of all, analyzes the symptomatology manifested by the patient and verifies the presence or absence of some typical disorders of the SMA, such as:
- Weakening and softness of the muscles
- Sudden muscle contractions
- Reduced or absent tendon reflexes
Afterwards, he makes a brief inquiry into the patient's family history, to see if anyone else in the family (parents, grandparents or siblings) has suffered or suffers from the same symptoms. The reason for this is simple: SMA is an inherited genetic disease that could be passed on from generation to generation.
The physical examination is the first step to identify SMA, but it is worth remembering that, for a diagnostic confirmation, genetic tests are required on the patient's DNA.
NB: Clearly, if the patient is a child, the closest parents and relatives are questioned.
ELECTROMYOGRAPHY
Electromyography ( EMG ) is used to evaluate the activity of motor neurons and the muscle contraction they trigger. The principle on which this electrical examination is based is rather complicated. Suffice it to say that surface electrodes (applied to the skin) are used to measure the extent of the nervous signal.
In a patient with SMA, this signal is altered.
GENETIC TESTS
Genetic tests dispel any doubt about the diagnostic hypotheses made previously.
Going to analyze a sample of the patient's blood (it is sufficient, therefore, a normal collection), one is able to observe every single chromosome and an eventual anomaly.
Genetic characteristics of SMA (type I, II, III, IV): | |
| Chromosome | 5, autosomal (or non-sexual) |
| Gene | SMN1 |
| Type of mutation | Deletion (ie absence of a stretch of DNA) |
| Missing genetic trait | Exon 7 |
PRENATAL DIAGNOSIS
If you have valid reasons for believing that your child may be suffering from SMA (such as, for example, a close family member suffering from the disease), parents can request specific genetic tests on the fetus.
A valid reason is needed, as the methods used for taking a fetal sample can be dangerous for the child.
- Chorionic villus sampling : a small placenta fragment is removed and analyzed in the laboratory. The exam is performed between the tenth and the 13th week of pregnancy.
- Amniocentesis : a small sample of amniotic fluid, a liquid that wraps and protects the fetus from external insults, is taken and analyzed in the laboratory. The exam takes place between the 15th and 20th week of pregnancy.
Treatment
Being a genetic disease, spinal muscular atrophy is currently incurable.
However, specific therapeutic measures can be put into practice, aimed at alleviating and slowing the progressive worsening of symptoms and improving patients' standard of living.
The success of the therapy depends, in large part, on the seriousness of the SMA : the type I and the type II have a dramatic outcome and, especially in the first case, the treatments are useless; type III and type IV, on the other hand, can be dealt with fairly successfully.
PHYSICAL EXPERIENCE AND PHYSIOTHERAPY
Patients with SMA derive enormous benefits from physical activity (adequate, of course, to the patient's possibilities), as it promotes cardiovascular well-being, prevents joint stiffness and improves motor skills in general.
For a good result it is good to consult an experienced physiotherapist and be steadfast in "training".
However, it should not be forgotten that the improvements and benefits depend a lot on how severe the form of SMA is.
NUTRITION AND FEEDING
Some patients with spinal muscular atrophy have considerable difficulty in properly chewing food and swallowing them, so much so that they run the risk of suffocating or suffering from malnutrition.
To avoid these dangerous consequences, it is essential to resort to feeding supports, such as the gastric nose tube or gastrostomy surgery, and to rely on a nutritionist who will plan a diet that is suited to the patient's needs.
MECHANICAL VENTILATION
In patients with mild breathing difficulties, respiratory exercises and so - called non-invasive ventilation (oronasal mask, mouthpiece, etc.) may suffice; in the most severe cases, instead, a tracheostomy operation is needed, with which the patient is intubated at the level of the trachea and connected to an artificial respirator.
respiratory gymnastics in cases of SMA
Those who suffer from diseases such as SMA, in addition to breathing with difficulty, also have problems coughing; cough is a fundamental act to expel foreign material (saliva, food, nasal secretions ...), which could mistakenly penetrate the pulmonary tracts and carry pathogenic bacteria.
With the respiratory gymnastics the thoracic muscles reinforcing the respiration and cough are strengthened (intended as gesture), in order to prevent pneumonia (of type ab ingestis ) and other pulmonary infections.
CARE OF SCOLIOSIS
Scoliosis is typical of severe spinal muscular atrophies, in which the muscles of the body are very weak.
When the deformation of the back is slight, it may be useful to use an orthopedic bust for conservative purposes; when, instead, it is severe, spinal fusion surgery is necessary, with which the column is straightened.
Prognosis
Prognosis depends on the severity of spinal muscular atrophy: type I and type II SMAs always have a dramatic outcome, while type III and IV SMAs can be successfully controlled.
