Classification Of Spinal Muscular Atrophy
The term spinal muscular atrophy (SMA) refers to a group of genetic disorders characterized by degeneration of anterior horn cells and resultant muscle atrophy and weakness.
Spinal muscular atrophy was originally described in 2 infant brothers by Guido Werdnig in 1891 and in 7 additional cases by Johan Hoffmann from 1893 to 1900.Although the eponym Werdnig-Hoffmann disease eventually became affixed to the severe infantile form of SMA, their cases actually were of intermediate severity; the first descriptions of severe infantile SMA were made by Sylvestre in 1899 and Beevor in 1903.A milder form of SMA in which patients retained the ability to stand and walk, with prolonged survival, was not formally described until the 1950s by Wohlfart, Fez, and Eliasson and then in more detail by Kugelberg and Welander.
All of these descriptions recognized and emphasized the seminal pathology as anterior horn cell degeneration as well as the pertinent clinical features of symmetrical, proximal predominant extremity weakness that also affects axial, intercostal, and bulbar musculature.Classification Of Spinal Muscular Atrophy
During the next half century, the variability in severity was further defined and characterized and controversy arose regarding whether the infantile, juvenile, and adult forms of SMA represented one or multiple diseases.
The multiple phenotypes were eventually formalized into a classification scheme at an International Consortium on Spinal Muscular Atrophy sponsored by the Muscular Dystrophy Association in 1991.This classification highlighted 3 SMA types based on the highest level of motor function (i.e., sitting or standing) and age of onset.
Subsequent modifications divided the type 3 category by age of onset, added a type 4 for adult-onset cases, and included a type 0 for patients with prenatal onset and death within weeks. Although there are degrees of severity even within an individual type, and as many as 25% of patients elude precise classification, this scheme remains relevant in the genetic era and provides useful clinical and prognostic information. There are several other types of SMA, including:Classification Of Spinal Muscular Atrophy
Spinal muscular atrophy with respiratory distress (SMARD) – a type of SMA that’s usually diagnosed during a baby’s first year of life and can cause serious breathing problems.
Kennedy’s disease, or spinobulbar muscular atrophy (SBMA) – a rare type of SMA that only affects men and usually starts in middle age; it doesn’t usually affect life expectancy.
Distal spinal muscular atrophy (DSMA) – a type of SMA that mainly affects the hands, feet, lower arms, and lower legs.
There is no cure for SMA, however, an understanding of the molecular genetics of SMA has led to the development of preclinical models and numerous potential therapeutic approaches. There is great excitement in the SMA Field because these therapeutic approaches have recently entered early phase clinical trials.Classification Of Spinal Muscular Atrophy