Spinal muscular atrophy

Aravindhan Veerapandiyan MD (

Dr. Veerapandiyan of University of Arkansas for Medical Sciences has no relevant financial relationships to disclose.

Originally released March 9, 1995; last updated July 5, 2019; expires July 5, 2022

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. The first U.S. Food and Drug Administration approved treatment, intrathecal nusinersen (an antisense oligonucleotide), shows dramatic improvements in motor milestones in patients with spinal muscular atrophy.

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 detects homozygous deletion of exon 7 in the SMN1 gene.


EMG remains a useful tool in the diagnosis of late-onset spinal muscular atrophy (type 3 and type 4).


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


• Nusinersen, the first FDA approved treatment for SMA, is effective and safe.


Gene therapy (Zolgensma - onasemnogene abeparvovec-xioi) is FDA approved for patients with all types of spinal muscular atrophy less than 2 years of age.

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 such as muscle weakness, muscle atrophy, fasciculations, and reduced or absent deep tendon reflexes can be seen.

When talking about spinal muscular atrophy, the clinician usually refers to the most common form, chromosome 5q-related spinal muscular atrophy, caused by mutations or biallelic deletions in the SMN1 (survival motor neuron 1) gene. Our knowledge about spinal muscular atrophy has greatly expanded in less than 2 decades, recognizing a number of non-5q forms of 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). Muscle biopsy showed large groups of atrophic fibers involving both type 1 and 2 fibers interspersed with fascicles of hypertrophied and normal 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 types of 5q related 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 non-5q forms of spinal muscular atrophy are clinically and genetically heterogeneous involving at least 30 different genes/chromosomal loci (Darras 2011; Pestronk 2018).

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