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Spinal Muscular Atrophy Workup

  • Author: Bryan Tsao, MD; Chief Editor: Amy Kao, MD  more...
Updated: Dec 23, 2015

Laboratory Studies

Laboratory testing

The creatine kinase (CK) level is typically normal in SMA type I and normal or slightly elevated in the other types.

CSF findings are normal.

Genetic testing

Both prenatal and postnatal tests are now commercially available.

Homozygous SMN1 gene deletion is 95% sensitive and nearly 100% specific for the diagnosis of SMA. In patients with suspected disease and no gene deletion, SMN1 copy testing with sequencing of coding regions of SMN1 copy (if present) is suggested.[38]  Molecular testing for homozygous deletion or mutation of the SMN1 gene allows efficient and specific diagnosis.[39]

The 1992 ISMAC found that the accuracy of prenatal prediction by means of chorionic villi sampling and amniocentesis was 88-99%.

Caution should be exercised when prenatal prediction is done in the presence of atypical features (see SMA variants in Physical) because these clinical variations may represent other pathogenic processes.



Other Tests

Most cases spare the cardiac system, and ECGs are normal.[40]

Electrophysiologic studies are useful in differentiating the spinal muscular atrophies from other neurogenic and myopathic diseases.[41, 42] With the exception of Kennedy and Davidenkow syndromes, sensory nerve conduction is normal in spinal muscular atrophy.

Compound motor action potentials (CMAPs) are low normal or reduced, depending on the severity of disease. In chronically weak muscles, CMAPs may be in the near-normal because of reinnervation and collateral sprouting. Motor velocities are normal. Modest slowing of motor conduction, when present, may accompany severe motor axon loss because of the loss of the fastest-conducting motor fibers.

In affected muscles, needle-electrode examination reveals widespread broad and polyphasic motor unit potentials (MUPs) firing in a reduced or rapid neurogenic recruitment pattern. Superimposed low-amplitude, short-duration, and polyphasic MUPs may be present. These configuration changes may resemble myopathic MUPs, but in the case of spinal muscular atrophy are instead due to early MUP reinnervation. Fibrillation potentials may be seen in limb and paraspinal muscles and are most striking in early or progressive spinal muscular atrophy. In late-juvenile and adult-onset forms, active motor axon loss is sparse. Fasciculation potentials are uncommon, but spontaneously firing motor unit action potentials (MUAPs) at 5-15 Hz have been described as a unique feature of SMA I and II.

Mild pseudomyotonic discharges have been observed in patients older than 6 years. However, these discharges are not specific for etiology and may be seen in chronic neurogenic disorders.



Muscle biopsy may necessary to differentiate spinal muscular atrophies from other neuromuscular disorders if genetic analysis is unrevealing. Muscle selection should be centered on clinically affected muscles but not to such a degree that degeneration renders the tissue unrecognizable.

Adequate results can be obtained with open or needle biopsy as long as the physician has adequate experience in the procedure and in processing of the tissue.

Electron microscopy can be used to evaluate for storage diseases.


Histologic Findings

Histologic findings depend on the stage and progression of disease. Initial changes include atrophy of muscle fibers with compensatory hypertrophy. This results in groups of large and small fibers (fiber-type grouping).

During the first 6-8 weeks of life, differentiating congenital fiber type disproportion and SMA may be difficult. In the chronic forms of SMA, secondary myopathic changes may be seen in addition to type grouping and may histologically resemble the muscular dystrophies.[43, 44]

Classic histologic findings include the following:

  • Degeneration and loss of spinal motor neurons with a neurogenic pattern of muscle morphology
  • Occasional neuronal chromatolysis with loss of myelinated axons in both anterior and posterior roots
  • A disproportionate loss of myelin in the thoracic and lumbar segments (especially in the corticospinal tracts) with relative sparing of the cervical cord
  • Motor neurons in the brainstem, notably in the hypoglossal nucleus. (Reactive gliosis and secondary degeneration in roots and nerves are seen. However, these findings are not necessarily pathognomic for the SMAs.)
Contributor Information and Disclosures

Bryan Tsao, MD Associate Professor, Department of Neurology, Loma Linda University; Chair and Service Chief, Department of Neurology, Loma Linda University Medical Center

Bryan Tsao, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.


Carmel Armon, MD, MSc, MHS Chair, Department of Neurology, Assaf Harofeh Medical Center, Tel Aviv University Sackler Faculty of Medicine, Israel

Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, Massachusetts Medical Society, American Academy of Sleep Medicine, American Stroke Association, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, Sigma Xi

Disclosure: Received research grant from: Neuronix Ltd, Yoqnea'm, Israel.

Theresa L LaBarte, DO Resident Physician, Department of Neurology, Loma Linda University Medical Center

Theresa L LaBarte, DO is a member of the following medical societies: American Academy of Neurology

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.

Kenneth J Mack, MD, PhD Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Additional Contributors

Robert J Baumann, MD Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine

Robert J Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

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