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The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, <jats:italic>SMN2<\/jats:italic> copy number, and functional status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HFMSE longitudinal changes were assessed using piecewise linear mixed\u2010effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12\u2010month assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A break point at age 7\u2009years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and <jats:italic>SMN2<\/jats:italic> copy number were not. The increase in response before the break point of age 7\u2009years is significant only for SMA IIIA (\u03b2 = 1.79, <jats:italic>p<\/jats:italic> &lt;\u20090.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (\u03b2 = \u22121.15, <jats:italic>p<\/jats:italic> &lt;\u20090.0001) and IIIB (\u03b2 = \u22120.69, <jats:italic>p<\/jats:italic> =\u20090.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real\u2010world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109\u20131117<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25900","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T07:52:47Z","timestamp":1600242767000},"page":"1109-1117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Clinical Variability in Spinal Muscular Atrophy Type <scp>III<\/scp>"],"prefix":"10.1002","volume":"88","author":[{"given":"Giorgia","family":"Coratti","sequence":"first","affiliation":[{"name":"Pediatric Neurology Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Centro Clinico Nemo Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Messina","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud University of Messina  Messina 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