Spinal muscular atrophy

Spinal muscle atrophy (SMA) is a severe neuromuscular disease caused by damage to motor neurons (motor neurons), which are located in the front horns of the spinal cord, as well as neurons of the motor nuclei in the brain stem. The type of inheritance is an autosomal recessive genetic defect caused by a mutation in the spinal motor neuron gene on the long arm of the 5th chromosome pair. In patients with SMA, it is completely or partially absent on the 5th pair of chromosomes. The nature and severity of the disease depends on how large the damaged area is, as well as on the condition of the other genes, the damage of which enhances the severity of the disease.

The incidence of SMA is approximately 1 case per 6000 live births. The involvement of motor neurons can be diffuse or limited to certain muscle groups and is characterized by progressive muscle atrophy, weakness and paralysis. 

Types of Spinal Muscular Atrophy (CMA)

I distinguish three types of the most common forms of SMA. 

Type I, or Verdnig-Hoffmann disease , refers to an easily recognizable form with an early onset. The most severe form, very weak newborns (disease onset 0-6months), difficulty controlling the head, weak crying and coughing, difficulty swallowing, unable to sit without support.

Chronic forms are divided into type II and type II I.

Type II (delayed Verdnig-Hoffmann form) – debut of the disease 7-18 months, able to sit on their own, delayed motor development and weight gain, mild cough, can not stand on their own.

Type III   (Kugelberg-Velander) with a later onset and predominantly proximal lesion. The debut of the disease after 18 months, can stand on its own, muscle weakness of varying degrees, hypermobility of the joints, can walk, but gradually loses the skill of walking. 

There is also type I V (the easiest) – walking patients with a debut of the disease in adulthood

Dubowitz (1999) proposed an addition in the form of a very severe form with a prenatal onset ( type 0 ), which ends in prenatal death or short-term survival only with emergency respiratory (respiratory) support.

It should be noted that the congenital form of SMA  Verdnig-Hoffmann   can be suspected even during fetal development. With a thorough history, some women noted that 1-3 months before birth, fetal movements became weak in intensity or were very rare. In such cases, a problematic birth occurs. From the first days of life, the following clinical manifestations of Werdnig Hoffmann’s disease (type I) are noted: symmetrical weakness of the muscles of the trunk and extremities, more noticeable proximal than distally, and prevailing in the lower extremities, weakness spreads quickly, tetraplegia occurs with some motion in the distal sections, especially in the upper limbs. Paralysis is symmetric with the involvement of muscles associated with the axial skeleton, neck, intercostal muscles, which leads to a characteristic deformation of the spine, chest, development of respiratory failure. Fasciculations (minor twitching) of the tongue and / or tremor of the fingers are also characteristic of SMA. In this case, violations of sensitivity or delays in psycho-speech development in a child are not observed.

The late form of Verdnig-Hoffmann amyotrophy, as we have said, has a later onset, the course of the disease is slower. The main symptoms are flaccid paralysis, muscle hypotension, areflexia (lack of reflexes), muscle fiber fibrillation.

Diagnosis of SMA: the first stage is the collection of anamnesis and examination of the child by a neurologist. An initial examination reveals clinical signs such as hypotension, weakness, more in the legs, weakness of the intercostal muscles, a paroxysmal type of breathing, and a number of other syndromes. The second stage is molecular genetic diagnostics. Genetic analysis for SMN 1 / SMN 2 is reliable and refers to first-line screening for suspected SMA. Additional diagnostic methods today are electroneuromyography (ENMG) – for the diagnosis of later (chronic) forms, tests for the concentration of creatine kinase (CPK) in the blood.

Treatment 

It should be noted that until a certain stage, this disease was considered incurable and very rapidly progressing. In 2007, the International Conference on Treatment Standards for AGR published recommendations on the diagnosis and treatment of this disease, as well as on orthopedic, respiratory and nutritional support for these patients, which is widely used all over the world. Also in 2016, the first drug for the treatment of SMA was approved, which is now used in many countries. All of the above has changed the approach of doctors and families to the treatment of spinal muscular atrophy, especially type I.