Spinal muscular atrophy

Nicolas Chrestian MD (Dr. Nicolas Chrestian of Laval University has no relevant financial relationships to disclose.)
Maryam Oskoui MD (Dr. Maryam Oskoui of McGill University is a site investigator in clinical trials with Ionis.)
Salvatore DiMauro MD, editor. (Dr. DiMauro, Director Emeritus of H Houston Merritt Clinical Center for the Study of Muscular Dystrophy and Related Diseases at Columbia University, has no relevant financial relationships to disclose.)
Originally released March 9, 1995; last updated March 20, 2017; expires March 20, 2020

This article includes discussion of spinal muscular atrophy, deletion 5q SMA, Dubowitz disease, inferior motor neuron disease, Kugelberg-Welander disease, SMA, and Werdnig-Hoffman disease. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Spinal muscular atrophy is a neurodegenerative disorder predominantly affecting the anterior horn cells. It is an autosomal recessive disorder with deletion of exon 7 of the SMN1 gene. The clinical classification is based on highest motor milestone achieved, and severity is, in part, associated with the number of SMN2 copies, an allelic gene of SMN1. Treatment is mainly symptomatic, with recent clinical trials showing promise.

Key points


• Spinal muscular atrophy is a neurodegenerative disorder primarily affecting the anterior horn cells.


• Diagnosis of spinal muscular atrophy is made by genetic testing, which looks for homozygous deletion of exon 7 in the SMN1 gene.


EMG remains a useful tool in the diagnosis of spinal muscular atrophy type 3.


• An interdisciplinary approach is essential to treat patients with spinal muscular atrophy.


• New promising emerging therapies are under development.

Historical note and terminology

Spinal muscular atrophy refers to a group of inherited disorders principally affecting the anterior horn cells. Signs of motor neuron disease can be seen, such as muscle weakness, atrophy, fasciculations, and reduced deep tendon reflexes.

When talking about spinal muscular atrophy, the clinician usually refers to the most common form caused by SMN1 mutations/deletion (survival of motor neuron). Our knowledge about spinal muscular atrophy has greatly expanded in less than 2 decades, recognizing both 5q spinal muscular atrophy and non–5q spinal muscular atrophy.

Werdnig and Hoffmann provided the first clinical description of a disorder with progressive weakness beginning in infancy, resulting in death at an early but inconsistent age, and characterized pathologically by anterior horn cell loss (Werdnig 1891; Hoffmann 1892). Acute, chronic, and late-onset forms of the disease were subsequently described. The formerly eponymous terms such as “Werdnig-Hoffmann disease,” “Dubowitz disease,” and “Kugelberg-Welander disease” have been replaced by the clinical classification of spinal muscular atrophy types 0 to 4. Electrophysiological studies showed evidence of acute and chronic denervation, without changes in nerve conduction velocities, confirming involvement of the motor neuron (Hausmanowa-Petrusewicz and Karwanska 1986). Changes in muscle biopsy were also those of acute and chronic denervation showing grouped atrophy and type grouping fibers with angulated fibers; postmortem findings included decreased numbers of motor neurons and gliosis in the anterior horns of the spinal cord and motor cranial nerve nuclei 5 and 7 to 12 (Hausmanowa-Petrusewicz et al 1980).

The single gene responsible for all 4 forms of spinal muscular atrophy was mapped to chromosome 5q11.12-13.3 in 1990 and was identified as the survival motor neuron gene (Gilliam et al 1990; Munsat et al 1990).

On the other hand, the classification of non–5q spinal muscular atrophy is less established, with a mix of terminology and overlapping extending from juvenile amyotrophic lateral sclerosis to hereditary distal motor neuropathy.

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