SMA is one of the neuromuscular disorders characterized by progressive muscle weakness resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.
Four subtypes have been defined according to the age of onset and severity of the disease:
type 1 (SMA1), the most severe form, with onset before six months of age;
type 2 (SMA2), with onset between 6 and 18 months of age;
type 3 (SMA3), with onset between childhood and adolescence;
type 4 (SMA4), the least severe form, with adult onset.
All types are characterized by muscle weakness and atrophy of varying severity, particularly affecting the lower limbs and respiratory muscles. The weakness is almost always symmetric and progressive. Scoliosis, muscle retractions, and joint contractures may occur.
Around 95% of cases of SMA are caused by homozygous deletions (either of exon 7, or of exons 7 and 8) in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. A second SMN gene (SMN2; 5q13.2) has also been identified and contributes to the production of only 10% of the full-length SMN protein. However, although there is some variation, disease severity in SMA is inversely correlated with the number of copies of the SMN2 gene, with patients with three or four copies more frequently manifesting SMA3/4, rather than SMA1.
Deletions of the NAIP (5q13.1) gene have also been identified and may play a role in modifying disease severity.
Transmission of SMN1 and NAIP deletions is autosomal recessive. Around 2% of cases are caused by de novo mutations. Genetic counseling should be offered to patients and their families.
Diagnosis is based on clinical history and examination and can be confirmed by genetic testing. Electromyography may also be performed.
Differential diagnoses include amyotrophic lateral sclerosis, congenital muscular dystrophies, congenital myopathies, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders.
At present, management of SMA patients remains symptomatic, involving a multidisciplinary approach that aims to improve quality of life. Physiotherapy and occupational and respiratory therapies are necessary. Noninvasive ventilation and gastrostomy may be required. Antibiotic therapy is used in case of pulmonary infection. The scoliosis and joint manifestations may require surgical correction. Patients may require a wheelchair, or use a corset/back brace for support.
The prognosis depends on the severity of the disease, which generally correlates with the age of onset: earlier-onset forms are generally associated with a poor prognosis, whereas life expectancy may be close to normal in later-onset forms. Death may occur due to respiratory insufficiency and infections.
Detection: We offer DNA test for the detection of the deletion of exon 7 of the SMN1 using the PCR technique and restriction analysis.
Specimen Requirements: genomic DNA is isolated from the peripheral blood, collected in 2 ml EDTA Vacutainer tube (lavender top). In case if DNA is already extracted, the minimum concentration should be 100ng/µl.
Transportation: The blood specimen can be stored in the refrigerator (for 1 or 2 days) and shipped to CMG at room temperature. In case of the DNA, it can be shipped to CMG at room temperature within 1-2 days.
Turnaround time: 10-15 days
For further information please contact:
Tel.: (+374 10) 544367
Fax: (+374 10) 544366