Spinal muscular atrophy: Definition, types, causes, diagnosis and treatments

Spinal muscular atrophy: Definition, types, causes, diagnosis and treatments

Proximal spinal muscular atrophy is a rare genetic neuromuscular disease. What are its causes and how is the diagnosis made? What types of treatments can be offered to patients with spinal muscular atrophy? The answers from Laure Gallois, clinical research nurse.

Spinal muscular atrophy: Definition

“Proximal spinal muscular atrophy (SMA) is a rare genetic neuromuscular disease (incidence 1/6000) which is characterized by a progressive muscle weakness not reaching the cognitive system at all”begins Laure Gallois, clinical research nurse at the clinical investigation center at the Necker-Enfants Malades hospital.

The latter would be due to a reduction in the number of muscle fibers within the muscle leading to motor impairment. Gold, “the degeneration of motor neurons located in the spinal cord ultimately leads to paralysis of the limbs as well as muscular atrophyshe specifies.

Causes and origin of spinal muscular atrophy

Spinal muscular atrophy known as SMA (acronym for “spinal muscular atrophy” in English) is therefore a pathology of genetic origin. “This disease is due to anomalies located in the SMN1 gene, located on chromosome 5reveals Laure Gallois.

For more information on this chromosomal pathology due to degeneration of motor neurons leading to muscle weakness, do not hesitate to visit the website of the Eclas association and AFM-Téléthon. According to the Telethon website (event organized each year by the French Association against Myopathies known as AFM, to finance research projects on neuromuscular genetic diseases), “where love between 80 and 100 the number of children affected by SMA who would be born each year in Europe“.

The different types and forms of spinal muscular atrophy

There are five types of rare neuromuscular diseases grouped under the acronym SMA. The type varies depending on the age of onset of symptoms. Indeed, the earlier the symptoms, the more severe the diagnosis :

Type 0: Prenatal phase

The diagnosis can be made in utero. Type 0 manifests itself, among other things, by a decreased fetal movements associated with major hypotonia as well as cardiac abnormalities. At birth, we find a respiratory failure which can lead, in certain cases, to the death of the infant during the first weeks of life.

Type I: severe infantile spinal muscular atrophy

Severe infantile spinal muscular atrophy, also called disease or Werdnig-Hoffmann syndromeis characterized by a progressive muscle weakness and muscle atrophy. “The diagnosis is made before the child is 6 months old and sometimes from birth”, reports the clinical research nurse at Necker Hospital. The diagnosis is initially made clinically: we can observe, among other things, a weak reflex reaction as well as significant hypotonia (muscle weakness), contrasted by rich visual contact. “This will subsequently be confirmed with a genetic sample which will highlight the absence of copies of the SMN1 gene”, she adds. Infants with this type of SMA have a life prognosis that can be poor due to respiratory failure.

Type II: intermediate infantile spinal muscular atrophy

SMA type II is the intermediate form of Dubowitz disease. Le diagnostic se pose between 6 and 18 months of the child’s life. It is characterized by a motor delay with difficulties, even inability of the child to crawl or walk. “Just like type 1, the respiratory failure can be life-threatening., notes Laure Gallois. However, she adds, “progression may stop spontaneously, leaving children with permanent but stable paralysis and a high risk of severe scoliosis with inherent complications”.

Type III: juvenile spinal muscular atrophy

Infantile spinal muscular atrophy type 3, known as juvenile SMA, is also known under the name Wohlfart-Kugelberg-Welander disease (ou encore syndrome de Kugelberg-Welander). “It can manifest itself from 15 months for babies and up to 19 years for children, reports the nurse from the clinical investigation center at Necker hospital. Unlike type I and II, in this juvenile form of the disease, walking is acquired. Symptoms side, they begin to manifest themselves by a muscle weakening, initially in the legs and hips, then in the arms and shoulders. A greater or lesser degree of discomfort may appear in the lower limbs which may require, depending on the patient, the use of a wheelchair in adulthood. The big positive difference with other types of amyotrophies is that generally, SMA type III does not cause no breathing problems. The life expectancy of patients is then not reduced.

Type IV: SMN1-related proximal spinal muscular atrophy (SMA) type IV

In case of type IV amyotrophy, the appearance of symptoms occurs after the age of 30. “THE symptoms are less severe than Type III and the progression is often slower, causing slight tremors of the hands, but not affecting walking function.notes Laure Gallois.

How is the diagnosis carried out?

Whatever the type of SMA, the diagnosis is based on thephysical examination. It is then confirmed by a genetic blood sampling highlighting the absence of copies of the SMN1 gene. Currently, “the High Authority for Health (HAS) is taking action to assess the relevance of including SMA in the national DNN program (Guthrie Test done at birth) which would allow early management of the disease”reports the clinical research nurse.

In a recommendation published in July 2023, the Haute Auroité de Santé (HAS) underlines in particular the importance of the extension in Europe of neonatal screening (DNN) aimed at detecting certain rare but serious diseases such as spinal muscular atrophy from birth. The objective: to implement, before the appearance of symptoms, appropriate measures in order to avoid or limit the negative consequences of these diseases on the health of children. In Europe, this screening is the subject of a national program.

Treatments and support

Unfortunately, there is no treatment that can completely cure proximal spinal muscular atrophy. However, as the clinical research nurse at Necker Hospital explains, there are three available drugs having an impact on the production of the SMN protein thus compensating for the SMN1 deficiency : Spinraza®, Zolgensma® and Evrysdi®. The latter, Evrysdi® is, as explained in the French medical reference manual Vidal, a new active ingredient in spinal muscular atrophy, available in pharmacies in the form of an oral solution (risdiplam). Alongside medical treatment, multidisciplinary care young patients is essential.

This follow-up may involve examinations and care carried out by pediatric neurologists, clinical geneticists, functional rehabilitation doctors, pediatricians, orthopedic surgeons, physiotherapists, occupational therapists, psychomotor therapists, psychologists and dietitians. “This multidisciplinary care would make it possible to identify orthopedic, respiratory and nutritional problems in particular”, underlines Laure Gallois. And she specifies, “once identified, these attacks can then be treated by specialists who will monitor the effectiveness and acceptability of the devices.”