NORD gratefully acknowledges Barry Russman, MD, Professor of Pediatrics and Neurology, Oregon Health Sciences University and Shriners Hospital for Children, for assistance in the preparation of this report.
The following resource from Cure SMA provides a description of symptoms, as well as videos to assist with early diagnosis:
SMA type 0 is the most severe form of the disease and is characterized by decreased fetal movement, joint abnormalities, difficulty swallowing and respiratory failure.
SMA type 1 is the most common type of SMA and is also a severe form of the disease. Infants with SMA type 1 experience severe weakness before 6 months of age and never sit independently. Muscle weakness, lack of motor development and poor muscle tone are the major clinical manifestations of SMA type I. Infants with the gravest prognosis have problems sucking or swallowing. Some show abdominal breathing in the first few months of life. Muscle weakness occurs on both sides of the body and the ocular muscles are not affected. A twitching of the tongue is often seen. Intelligence is normal. Most affected children die before two years of age but survival may be dependent on the degree of respiratory function. For more information about SMA type 1, chose “Werdnig Hoffman” disease as your search term in the Rare Disease Database.
The onset of weakness in SMA type 2 patients is usually between 6 and 12 months. Affected children are able to sit independently early in development but are unable to walk even 10 feet independently. A trembling (tremor) of the fingers is almost always seen in SMA type 2. Approximately 70% of those affected do not have deep tendon reflexes. Those affected with SMA type 2 are usually not able to sit independently by the mid-teens or later.
Patients with SMA type 3 (Kugelberg-Welander syndrome) learn to walk but fall frequently and have trouble walking up and down stairs at 2-3 years of age. The legs are more severely affected than the arms. The long-term prognosis depends on the degree of motor function attained as a child. For more information about SMA3 chose “Kugelberg Welander syndrome” as your search term in the Rare Disease Database.
The onset of muscle weakness for those with SMA type 4 is after age 10 years; these patients usually are ambulatory until age 60 years.
Complications of SMA include scoliosis, joint contractures, pneumonia and metabolic abnormalities such as severe metabolic acidosis and dicarboxylic aciduria.
SMA types 0, 1, 2, 3 and 4 are inherited as autosomal recessive genetic disorders and are associated with abnormalities (mutations) in the SMN1 and SMA2 genes on chromosome 5 at chromosomal locus 5q11-q13. SMA1 is thought to be the primary disease-causing gene. Approximately 95-98% of affected individuals have deletions in the SMA1 gene and 2-5% have specific mutations in the SMA1 gene that result in a decreased production of the SMN protein. When three or more copies of the SMA2 gene are also present, the disease may be milder.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Biological or surrogate markers for SMA are under development. These potential surrogate markers studied to date include:
1) Measuring the amount and ratio of full-length and truncated SMN2 RNA transcripts as well as the amount of SMN protein from white blood cells or fibroblast culture.
2) Counting motor units (Motor Unit Number Estimation, or MUNE) which have shown correlation with the SMN2 copy number, age, and function.
3) Quantitative ultrasound in assessing muscle changes in patients with SMA.
4) Electrical impedance myography.
5) The compound action potential determined by EMG in children with SMA. The authors point out that MUNE is difficult and not as reliable as initially thought. A longitudinally study of the surrogate markers will be necessary before any particular one can be used in an intervention study.
The diagnosis of SMA is suspected when symptoms are present and the diagnosis can be confirmed with molecular genetic testing. Molecular genetic testing is used to determine if a mutation is present in the SMN1 gene. SMA types 0, 1, 2, 3 and 4 are caused by a partial or complete loss of the SMN1 gene and about 95% of those affected will show a deletion of both copies of a specific portion (exon 7 or exon 8) of the gene. About 5% of those affected will show a deletion of exon 7 in one copy of the SMN1 gene and a different mutation in the other copy of the SMN1 gene. Molecular genetic testing can also be used to determine the number of copies of the SMN2 gene.
Prior to the availability of molecular testing, neurophysiologic studies and muscle biopsy were used for diagnosis, but these tests are no longer necessary unless SMN gene testing is normal.
Carrier testing for SMA is available using a molecular genetic test in which the number of copies of the SMN1 gene is determined.
Molecular genetic testing for the VAPB gene is available to diagnose Finkel type SMA.
Care for individuals with SMA is symptomatic and includes physical therapy, occupational therapy, monitoring of respiratory function and nutritional status, orthotics and adaptive equipment. Respiratory support for SMA1 using a breathing machine called BiPAP (bi-level positive airway pressure) has been shown to increase comfort and life expectancy in some affected children.
Genetic counseling is recommended for affected individuals and their families.
The management of children with spinal muscular atrophy starts with the diagnosis and classification into 1 of the 5 categories. Health issues specific to spinal muscular atrophy are as follows:
Pulmonary management: Children with SMA1 can survive beyond 2 years of age when offered tracheostomy or noninvasive respiratory support.
An intermittent positive-pressure breathing device (mechanical in-exsufflator) has proven effective.
Nutrition: Bulbar dysfunction is universal in SMA1 patients. Early gastrostomy should be considered as part of the management of such patients. The bulbar dysfunction eventually becomes a serious problem for spinal muscular atrophy II patients and only very late in the course of disease for spinal muscular atrophy III patients.
Scoliosis: Scoliosis is a major problem in most SMA2 patients and in half of SMA3 patients.
The vertical expandable prosthetic titanium rib (VEPTR) was approved by the FDA in 2004 as a treatment for thoracic insufficiency syndrome (TIS) in pediatric patients. TIS is a congenital condition where severe deformities of the chest, spine, and ribs prevent normal breathing and lung development. The VEPTR is an implanted, expandable device that helps straighten the spine and separate ribs so that the lungs can grow and fill with enough air to breathe. The length of the device can be adjusted as the patient grows. The titanium rib was developed at the University of Texas Health Science Center in San Antonio. It is manufactured by Synthes Spine Co.
Hip dislocation: Hip dislocation is another orthopedic concern in patients with spinal muscular atrophy. If the hip dislocation is asymptomatic, surgery is not indicated.
Behavior issues: Compared to siblings and normal controls, patients with spinal muscular atrophy were quite well adjusted. Concern was, however, raised about unaffected siblings, who had a 2 to 3-fold higher rate behavioral problems than normal children.
Sleep disorders: Sleep-disordered breathing may develop prior to respiratory failure. Night-time use of continuous positive airway pressure with a nasal mask may be helpful.
In 2017, Spinraza (nusinersen) was FDA approved as the first drug to treat children and adults with SMA. Spinraza is manufactured by Biogen.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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