Practice Essentials
Spinal muscular atrophies (SMAs) represent a rare group of inherited disorders that cause progressive degeneration of the anterior horn cells of the spinal cord. The exact cause of the degeneration is unknown. Loss of these cells results in a progressive lower motor neuron disease that has no sensory involvement and that is manifested as hypotonia, weakness, and progressive paralysis. Kugelberg Welander spinal muscular atrophy (also known as Wohlfart-Kugelberg-Welander syndrome or mild SMA) is a milder form of SMA, with symptoms typically presenting after age 18 months. [1, 2, 3]
SMAs were first described in the 1890s, by Guido Werdnig, a physician from the University of Vienna, in his lecture "On a Case of Muscular Dystrophy with Positive Spinal Cord Findings." Soon after, Professor Johann Hoffmann from Heidelberg University presented a paper describing a syndrome of progressive atrophy, weakness, and death during the early childhood period of siblings with genetically normal parents. Both physicians conducted autopsies on their patients and found severe atrophy of the ventral roots of the spinal cord. They also found histologic evidence of loss of motor neurons in the anterior horn cells of this region. Hoffmann called the syndrome spinale muskelatrophie (spinal muscular atrophy).
In the early 1960s, Byers and Banker classified SMA into categories based on the severity and age of onset of the symptoms, in an effort to predict prognosis.
Pathophysiology
Spinal muscular atrophy (SMA) is caused by successive motor unit degeneration. Muscle atrophy, caused by a progressive loss of the anterior horn cells in the spinal cord, is universal. The motor nuclei in the lower brainstem, usually those of cranial nerves V-XII (V, VII, IX, XII), also may be involved. Various stages of degeneration can be observed histologically at these sites. As the nerve cells decrease in number, replacement gliosis, pyknosis, and secondary Wallerian degeneration in the roots and peripheral nerves are observed. These processes generally begin at the caudal end of the cord and typically are symmetrical. The lower limbs usually are affected sooner and more profoundly than are the upper limbs. This degeneration most often affects the proximal musculature before it impacts the distal. Note that, unlike in amyotrophic lateral sclerosis (ALS), no corticospinal tract involvement is seen in SMA.
A study by Querin et al involving adult patients with SMA type III or IV found that spinal cord gray matter had considerably atrophied between C2 and C6, while, possibly owing to an adaptive mechanism, the gray matter had grown denser in the motor and extramotor cortical regions. [8]
Epidemiology
Frequency
United States
Spinal muscular atrophy (SMA) has an estimated incidence of 1 case per 15,000 live births. The genetic carrier prevalence is 1:80.
International
SMA has an estimated incidence of 1 case per 15,000-20,000 live births worldwide.
Mortality/Morbidity
SMA types III and IV, unlike types I and II, are consistent with survival well into adulthood. [9] Significant morbidity occurs from progressive weakness, and patients may frequently fall or may have difficulty with stairs. Most patients use wheelchair mobility by their fourth decade of life. Scoliosis and joint contractures are also extremely common. Morbidity associated with these conditions often can be minimized with spinal surgery, as well as with aggressive physical therapy. Respiratory failure in SMA types III and IV is not as common as in types I and II. Respiratory complaints usually can be managed medically, and mechanical ventilation seldom is necessary. [10, 11, 12, 13]
Cardiovascular pathologies have frequently been found in cases of SMA. A literature review by Wijngaarde et al reported that among these heart-related comorbidities, cardiac rhythm disorders most often accompanied milder forms of SMA, while structural cardiac disorders (primarily septal defects and cardiac outflow tract abnormalities) were most commonly associated with more severe SMA. [14]
A study by Souza et al of 20 individuals with SMA type IV determined limb-girdle muscle weakness to be the most frequent clinical symptom, being found in 75% of the patients. Fasciculations and absence of tendon reflexes made up the most frequent neurologic findings, occurring in 45% and 90% of patients, respectively. The investigators also found that disease duration correlated with functional scale scores, including those on the Hammersmith Functional Motor Scale Expanded, the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised, the Revised Upper Limb Module, and the Spinal Muscular Atrophy Functional Rating Scale. Such correlation was also reported for the 6-minute walk test and the Timed Up and Go test. [15]
Race
Spinal muscular atrophy (SMA) affects all races equally.
Sex
Spinal muscular atrophy affects males and females at the same rate; however, disease progression is more severe in males.
Age
The age of onset for spinal muscular atrophy is discussed above in the Background section.
