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Spinal Muscle Atrophy

  • Author: Joseph T Cox, MD; Chief Editor: Jeffrey A Goldstein, MD  more...
 
Updated: Oct 14, 2014
 

Background

Spinal muscle atrophy (SMA; also known as spinal muscular atrophy) is an autosomal recessive hereditary disease characterized by progressive hypotonia and muscular weakness. The characteristic muscle weakness occurs because of a progressive degeneration of the alpha motor neuron from anterior horn cells in the spinal cord. The weakness is more severe in the proximal musculature than in the distal segments.

In certain patients, the motor neurons of cranial nerves (especially cranial nerves V-XII) can also be involved. Sensation, which originates from the posterior horn cells of the spinal cord, is spared, as is intelligence. Several muscles are spared, including the diaphragm, the involuntary muscles of the gastrointestinal system, the heart, and the sphincters.[1, 2, 3, 4]

In 1890, Werdnig described for the first time the classic infantile form of SMA.[5] Many years later, in 1956, Kugelberg and Welander described the less severe form of SMA.[6] Werdnig, in 1890,[5] and Hoffman, in 1891,[7] reported cases of muscular dystrophy occurring in infants that were otherwise similar to cases of muscular dystrophy found in older children and adults (eg, Duchenne muscular dystrophy).

SMA is the most common diagnosis in girls with progressive weakness. It is one of the most common genetic causes of death in children.

SMA is commonly divided into four types on the basis of patient age at onset, as follows:

  • Type I (Werdnig-Hoffmann disease) - Onset between birth and age 6 months
  • Type II - Onset between the ages of 6 and 12 months
  • Type III (Kugelberg-Welander disease) - Onset between the ages of 2 and 15 years
  • Type IV - Adult onset
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Pathophysiology

SMA is caused by a mutation in the survival motor neuron gene. This gene is normally inactive during the fetal period and allows normal apoptosis in the developing fetus. The gene becomes active in the healthy mature fetus to stabilize the neuronal population. In its absence, programmed cell death persists.[8] The mechanism and timing of abnormal motor neuron death remain unknown.[9, 10]

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Epidemiology

Frequency

United States

The incidence of SMA is about 1 case in 15,000-20,000 (5-7 per 100,000) live births. The prevalence of persons with the carrier state is 1 in 80.

In North Dakota, the incidence is about 1 case in 6720 (15 per 100,000) live births, the prevalence is 1.5 cases in 10,000, and the prevalence of persons with the Werdnig-Hoffman disease carrier state is 1 in 41.[11] SMA appears to be 3-10 times more common in North Dakota than in other areas.

SMA is the most common degenerative disease of the nervous system in children. After cystic fibrosis, it is the second most common disease inherited in an autosomal recessive pattern that affects children. It is the leading heritable cause of infant mortality.[12]

International

The incidence of SMA is generally higher in Central and Eastern Europe than in Western Europe.

In England, the incidence is 1 case in 24,100 (4 per 100,000) live births. Prevalence is 1.2 cases per 100,000 population. In Italy, the incidence is 7.8 cases in 100,000 live births (all types). In Germany, the incidence of Werdnig-Hoffmann disease is 1 case in 10,202 (9 per 100,000) live births.[13] The incidence of SMA in Slovakia is 1 case in 5631 (18 per 100,000) live births (all types). In Poland, the incidence of Werdnig-Hoffmann disease is 1 case in 19,474 (5 per 100,000) live births.

Mortality/Morbidity

In SMA, death occurs because of respiratory compromise. The younger the patient is at onset, the worse the prognosis is. The overall median age at death exceeds 10 years. Intelligence is unaffected by SMA.

Race

The incidence of SMA in black Africans is very low.

Sex

Males are more commonly affected with SMA than females are. The male-to-female ratio is 2:1. The clinical course in males is more severe. Life expectancy has not been demonstrated to be influenced by sex.[14] As the age at onset increases, incidence of SMA in females decreases. With age at onset older then 8 years, females are affected much less frequently. In cases in which the patient is older than 13 years at onset, incidence in females is the exception.

Age

The three different types of SMA that occur in the pediatric population are genetically similar but differ with respect to patient age at presentation and clinical course, as follows:

  • Type I (Werdnig-Hoffmann disease) - This acute infantile SMA is usually identified in patients from birth to age 6 months
  • Type II - This chronic infantile SMA is diagnosed in infants aged 6-12 months
  • Type III (Kugelberg-Welander disease) - This type of SMA is diagnosed in children aged 2-15 years
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Contributor Information and Disclosures
Author

Joseph T Cox, MD Resident Physician, Department of Orthopedic Surgery, Sports Medicine and Rehabilitation, Wright State University, Boonshoft School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jeffrey A Goldstein, MD Clinical Professor of Orthopedic Surgery, New York University School of Medicine; Director of Spine Service, Director of Spine Fellowship, Department of Orthopedic Surgery, NYU Hospital for Joint Diseases, NYU Langone Medical Center

Jeffrey A Goldstein, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Orthopaedic Association, North American Spine Society, Scoliosis Research Society, Cervical Spine Research Society, International Society for the Study of the Lumbar Spine, AOSpine, Society of Lateral Access Surgery, International Society for the Advancement of Spine Surgery, Lumbar Spine Research Society

Disclosure: Received consulting fee from Medtronic for consulting; Received consulting fee from NuVasive for consulting; Received royalty from Nuvasive for consulting; Received consulting fee from K2M for consulting; Received ownership interest from NuVasive for none.

Additional Contributors

James F Kellam, MD, FRCSC, FACS, FRCS(Ire) Professor, Department of Orthopedic Surgery, University of Texas Medical School at Houston

James F Kellam, MD, FRCSC, FACS, FRCS(Ire) is a member of the following medical societies: American Academy of Orthopaedic Surgeons, Orthopaedic Trauma Association, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Acknowledgements

Alvin H Crawford, MD, FACS Professor of Pediatrics and Orthopedic Surgery, University of Cincinnati College of Medicine; Director, Division of Pediatric Orthopedic Surgery, Department of Orthopedic Surgery, Cincinnati Children's Hospital Medical Center

Alvin H Crawford, MD, FACS is a member of the following medical societies: Ohio State Medical Association and Scoliosis Research Society

Disclosure: Nothing to disclose.

Jose A Herrera-Soto, MD Assistant Program Director of Pediatric Orthopedic Fellowship, Orlando Regional Healthcare

Jose A Herrera-Soto, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, North American Spine Society, Pediatric Orthopaedic Society of North America, and Scoliosis Research Society

Disclosure: Nothing to disclose.

Charles T Mehlman, DO, MPH Professor of Pediatrics and Pediatric Orthopedic Surgery, Division of Pediatric Orthopedic Surgery, Director, Musculoskeletal Outcomes Research, Cincinnati Children's Hospital Medical Center

Charles T Mehlman, DO, MPH is a member of the following medical societies: American Academy of Pediatrics, American Fracture Association, American Medical Association, American Orthopaedic Foot and Ankle Society, American Osteopathic Association, Arthroscopy Association of North America, North American Spine Society, Ohio State Medical Association, Pediatric Orthopaedic Society of North America, and Scoliosis Research Society

Disclosure: Nothing to disclose.

References
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Spinal muscle atrophy, Werdnig-Hoffman disease. Small muscle fibers within separate muscle fascicles.
Spinal muscle atrophy, Werdnig-Hoffman disease. Marked variation in muscle fiber size as well as a relative increase in associated connective tissue.
Spinal muscle atrophy, Kugelberg-Welander disease. Marked variation in muscle fiber size along with increased perimysial connective tissue.
Spinal muscle atrophy, Kugelberg-Welander disease. Muscle fiber variation with some demonstrating internal nuclei.
Spinal muscle atrophy. At age 4 years, this boy's chest radiograph already reveals the presence of significant 32° left thoracic scoliosis. His diagnosis is type I spinal muscle atrophy (Werdnig-Hoffmann disease). This radiograph captures the lumbar curvature incompletely.
Spinal muscle atrophy. By age 6 years, the child's curve is starting to decompensate. Note the development of a right-sided truncal shift. He now has a 40° thoracic curve and a 60° lumbar curvature.
Spinal muscle atrophy. Spine anteroposterior view. The spinal curvature is progressing. The lumbar curve now is 70° and the thoracic curve is 35°. Note that one can now clearly see that the right hip is dislocated. Also note the marked pelvic obliquity in this patient.
Spinal muscle atrophy. By age 9 years, this patient with type I spinal muscle atrophy now has a thoracic curve of 60° and a lumbar curve of 110°. Note that the patient has a tracheostomy tube and a nasogastric tube as well.
Spinal muscle atrophy. Immediate postoperative anteroposterior radiograph of the patient at age 9 years. The thoracic curve is now at 18° and the lumbar curve is 35°, which represents more than 67% curvature correction.
Spinal muscle atrophy. Immediate postoperative lateral view with good sagittal balance.
Spinal muscle atrophy. Follow-up radiographs in the patient at age 13 years reveal some spinal decompensation. Note the so-called coat hanger appearance of the ribs in the patient's dysplastic right hemithorax.
Spinal muscle atrophy. Anteroposterior radiograph of the pelvis demonstrating right hip dislocation.
Spinal muscle atrophy. Lauenstein lateral view of the hips on the patient with spinal muscle atrophy type I. Note the near universal pelvic dysmorphology (eg, widened obturator foramina) in addition to the dislocated right hip.
 
 
 
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