Spinal Muscular Atrophy (SMA)
It is an autosomal recessive illness, ie both parents must have damaged genetic material (mutations) or a de novo mutation without damage in the parents. It is the third most common in Greece (1-14 births in Greece, 1: 6000 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 (SMN1 and SMN2). When there is a mutation in SMN1, it leads to illness, but the severity of the symptoms is also dependent on the mutations of SMN2, which, the fewer they are, less symptoms occur. There are rarer mutations in other parts of the genetic material, such as chromosome X.
The general rule is that the shorter the age of 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.
Types with different mutations
- Scapuloperoneal SMA,
- Pons-cerebellar hypoplasia with SMA,
- Neonatal X-linked SMA with arthrogryposis,
- SMA with type I respiratory distress.
In the above cases, there are additional symptoms of pons-cerebellar degeneration, diaphragmatic paralysis, contractions, 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, electromyography and genetic testing.
Prevention can be achieved through prenatal testing, when there is a familiar history, with preimplantation diagnosis at the beginning of pregnancy, and with the detection of vectors 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. This makes it possible to detect any changes over time and to identify elements that require intervention.
Family Education and Counseling
Upon diagnosis family should be informed about the progression, pathogenesis, categorization and prognosis of the disease 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.
SMA's main and major problems that need to be addressed are:
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, the 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 the 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:
Suggested measures to treat gastrointestinal dysfunction:
Proposed measures for the management of developmental problems:
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 the vertebral column.
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 supplementation.
Information about clinical trials conducted globally: https://www.centerwatch.com/clinical-trials/listings/condition/721/spina... 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?u....
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?u...
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?u...
Muscular Dystrophy Association