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Proximal hereditary spinal muscular atrophy (SMA) is caused by homozygous deletion of the survival motor neuron (SMN) 1 gene and has a wide range of severity.1 Onset may occur prenatally up to the fourth decade of life, and motor deficits range from neonatal hypotonia to mild weakness in adulthood. The current classification of SMA distinguishes five SMA types (ie, type 0–4) based on the combination of age at onset and two acquired gross motor milestones.1 ,2 Distinction of additional subtypes based on differences in the age at onset, first for SMA type 3 (ie, 3a and 3b) and more recently for type 1 (ie, 1a–1c), has been proposed. This may help to further clarify differences in prognosis within SMA types and to balance baseline characteristics in clinical trials. We aimed to gain further insight into the added predictive value of motor milestones for the occurrence of SMA outcome or common complications, that is, death, respiratory insufficiency, scoliosis surgery and loss of ambulation. We included SMN2 copy number in our analysis, since this is the most important genetic biomarker of severity.3
Patients and methods
We enrolled patients with SMA types 1–4 between September 2010 and August 2014.
Methods are described in the online supplementary file.
The clinical diagnosis of SMA was genetically confirmed in 200 patients. SMN2 copy number varied from 1 to 5 and overlapped between SMA types. SMN2 copy number correlated inversely with SMA type (p<0.001; table 1). Clinical characteristics are summarised in table 1.
Motor milestones defined SMA type 1–3 in case of discrepancies with age of onset. SMA classification was eventually changed in 18 patients (9%) because of acquisition of new motor milestones.
We included 42 patients with SMA type 1 (table 1). Three patients had the most severe phenotype, type 0/1a, …
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