Spinal Muscular Atrophy (SMA)

It is an autosomal recessive illness, ie both parents must have mutations or a de novo mutation. It is the third most common in Greece (1-12 births in Greece, 1: 6000-11.000 births per year and globally) and concerns the lack of a protein (SMN), which is of major importance in the function of motor neurons, namely nerve cells who control the muscles. There are two regions that can possibly be mutated in the genetic material, the so called survival motor neuron genes (SMN1 and SMN2 genes). When there is a mutation in SMN1, it leads to illness, but the severity of symptoms is also dependent on the mutations of SMN2, which, the fewer they are, less symptoms occur. There are also rarer mutations in other parts of the genetic material, such as on chromosome X.


The general rule is that the earlier the onset of symptoms, the more severe the progression of the disease is. There are subclasses of the disease, but in most patients there is symmetrical muscle weakness mainly in the center of the body, on shoulders, hips, thighs and upper back, with legs showing weaker than arms and affecting neck and face. Complications occur when respiratory muscles and swallowing muscles are involved, including severe respiratory infections. In addition, there is loss of reflexes, the presence of horror and scoliosis, and also kyphosis and other bone problems.


Τype 0 – Symptoms occur during pregnancy, causing death at that time or directly after birth. .
Τype Ι (or Werdnig-Hoffmann) – Symptoms occur during the first months of life, and the newborn is characterized by muscle weakness affecting breathing function, movement and swallowing. There is generalized hypotonia and weak cry. (Most frequent type, 50 -70%)
Τype ΙΙ – Occurs at children aged 7 – 18 months old. It is presented with great variety of symptoms in each child, but assisted standing and /or walking, breathing problems, difficulties of chewing and swallowing are frequent.
Τype ΙΙΙ (or Kugelberg – Welander) – Muscle weakness occurs after the age of 18 months gradually even until adulthood. Usually the walking is not assisted, but progressively the use of a wheelchair is necessary.
Τype IV – Occurs during adulthood and there is the possibility of mild muscle weakness.

Types with different mutations

– Scapuloperoneal SMA,

– Pons-cerebellar hypoplasia with SMA,

– Neonatal  X-linked SMA with arthrogryposis,

– SMA respiratory distress type I.

In the above cases, there are additional symptoms of pons-cerebellar degeneration, diaphragmatic paralysis, contractures, weakness and respiratory failure.


It can be achieved by taking a personal and family history, with appropriate clinical examination, where muscle atrophy or weakness is present in torso, upper and lower limbs, muscle biopsy (rarely), electromyography (rarely) and genetic testing mainly.


Prevention can be achieved through prenatal testing, when there is a familiar history, with preimplantation diagnosis at the beginning of pregnancy, newborn screening and with screening of carriers in patient families or the general population.

Neuromuscular and Myoskeletal Evaluation

Among the tests included in the clinical examination is the physical that focuses on the neuromuscular system and its lesions, depending on the level of severity. This includes various ways of assessing the strength and extent of joint mobility using special scales and timed tests. They are usually performed every 6 months, unless there are special circumstances. There is the options of detecting any changes over time and identify elements that require intervention.

Family Education and Counseling

Upon diagnosis family should be informed about the progression, pathogenesis, categorization and prognosis by the responsible physician, as a plan of multidisciplinary care that should be developed including monitoring by a pediatrician, a geneticist, a pneumologist, a gastroenterologist, a nutritionist, an orthopaedic as well as rehabilitation scientists (eg physiotherapists). Additionally, advocacy groups need to be interconnected.

Respiratory care

SMA’s main and major problems that need to be addressed are:

  1. The affected function of cough, leading to the inability to eliminate secretions.
  2. Ventilation especially during sleep.
  3. The under-developed chest wall and the lungs.
  4. Recurrent infections that aggravate muscle weakness.

The clinical assessment should be every 3-6 months depending on the severity of each condition. There is a series of specialized tests (eg sleep study) and some of the interventions that can be done are airway cleaning with special devices, non-invasive ventilation at night or even continuous, even as a preventive measure, hydration management and nutritional support, inhalation of bronchodilators and other appropriate drugs and of course special management in cases of acute respiratory infections, both pre- and post-operative. Physiotherapy is also a major contributor to appropriate breathing exercises. Annual vaccinations against pneumococcus and influenza virus are indicated. In serious cases, if discussed with the family and there are similar indications, invasive ventilation can be performed via tracheostomy.

In order to deal with an emergency at home, family must be informed, given detailed instructions and trained accordingly to intervene immediately. If it is necessary to transfer and stay in a special rehabilitation center or hospital unit, the necessary actions are taken in proportion to the indications and protocols for respiratory and nutritional support and always in cooperation with the rest of the multidisciplinary team (physiotherapists, speech therapists, psychosocial services, palliative care) in order to avoid any complications.

Consideration must be given to the prospects of new therapies in order to anticipate measures to address their possible complications.

Gastrointestinal and Nutritional Care

The presence of eating and swallowing problems, gastrointestinal dysfunction (gastroesophageal aspiration, constipation, dilation), developmental problems or hyperactivity are common, and if there is respiratory problem, it is also burdened with the gastrointestinal tract.

Proposed measures to manage nutritional difficulties:

  1. Evaluation by speech therapist or occupational therapist as well as assessment of obesity and glucose metabolism.
  2. Food composition adjustment to facilitate swallowing, combined with the necessary hydration, probiotics and regulatory factors of intestinal function.
  3. Correct posture and possible use of ancillary devices.
  4. In advanced situations and according to needs, gastrostomy or nasogastric tube or nasopharyngeal tube is used.
  5. No specific diet is recommended and caloric intake is calculated as usual.

Suggested measures to treat gastrointestinal dysfunction:

  1. Clinical evaluation.
  2. Administration of antiacids or gastric secretion inhibitors or even probiotics.

Proposed measures for the management of developmental problems:

  1. Get personal history and clinical assessment, weight control by analyzing data and development markers by a specialist nutritionist.
  2. Intake of calcium and vitamin D.
  3. Avoid fat intake and intake of protein supplements.
  4. In severe cases (type I and II) avoid fasting with intestinal or parenteral food because of an imminent risk of hypoglycemia.

Orthopaedic Care – Rehabilitation

Measures should be taken for muscle weakness, muscle stiffness, spinal deformities, restricted movement, pain, osteopenia and possible fractures.

Depending on the case and its severity, clinical assessments by physiotherapists and occupational therapists are recommended, special exercises in relation to stretching, body positioning and breathing, supporting devices and wheelchairs to facilitate movement and communication and, if necessary, corrective procedures of spine.

In terms of bone health directly associated with SMN 1 protein, possibilities of osteopenia and often fractures are high, and frequent bone density testing is required with appropriate examinations, annual tests to determine vitamin D amount and supplements.

Pharmaceutical Treatment

The natural history of Spinal Muscular Atrophy has already been changing, according to indications and with the contribution of the discovery and the approval of new compounds since 2017.

Spinraza (nusinersen): a compound of antisense oligonucleotide category, intrathecally administered, modifying the expression of SMN2 gene and increasing the production of SMN protein. (FDA and ΕΜΑ approved)
For further information: https://www.spinraza.com/

Zolgensma (onasemnogene abeparvovec – xioi): gene therapy, replacing the absent or non functional SMN1 gene, inducing the production of SMN protein. (FDA and EMA approved)
For further information: https://www.zolgensma.com/

Evrysdi (risdiplam): orally administered compound, inducing the production of SMN protein by the expression of SMN2 gene. (FDA approved)
For further information: https://www.evrysdi.com/

For more and updated information according to recently development,  you may read fyrther in the following booklet by SMA Europe:

Infopack for Clinical research in conducting Clinical trials for SMA_Part 1_SMA_Pathology, diagnosis, clinical presentation, therapeutic strategies and treatments

Information about clinical trials conducted globally: https://www.centerwatch.com/clinical-trials/listings/condition/721/spinal-muscular-atrophy/ and https://clinicaltrials.gov/ct2/home

For more and more recent and updated information on SMA Standards of Care, please refer to the following articles:

  1. R.S. Finkel el at, 218th ENMC International Workshop: Revisiting the consensus on standards of care in SMA, Naarden, The Netherlands, 19-21 February 2016, Neuromuscul. Disord., 2017, 27, pp. 596-605, https://drive.google.com/file/d/1RNX8L9imY7H_6xsB7WTkqjR5OqEUbiqe/view?usp=sharing.
  2. E. Mercuri et al, Diagnosis and management of Spinal Muscular Atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care, Neuromuscl. Disord., 2018, 28, pp. 103-115, https://drive.google.com/file/d/1oCnOJMu5hica6Fug7KPk7JIlBYKtWF98/view?usp=sharing.
  3. R.S. Finkel et al, Diagnosis and management of Spinal Muscular Atrophy: Part 2: Pulmonary and acute care; medications and immunizations; other organ systems; and ethics., 2018, Accepted Manuscript, Neuromuscul. Disord.,  https://drive.google.com/file/d/11zoR7bUX2792vNjqjMeqoSuY53GCaHjv/view?usp=sharing.


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