Clinical and radiological profile of patients with spinal muscular atrophy type 4

<jats:sec><jats:title>Background and purpose</jats:title><jats:p>Spinal muscular atrophy (SMA) is the most important cause of motor neuron disease in childhood, and continues to represent the leading genetic cause of infant death. Adulthood‐onset SMA (SMA type 4) is rare, with few isolated cases reported. The objective of the present study was to describe a cohort of patients with SMA type 4.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A cross‐sectional study was conducted to characterize clinical, genetic, radiological and neurophysiological features of patients with adulthood‐onset SMA. Correlation analysis of functional assessment with genetic, radiological and neurophysiological data was performed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Twenty patients with SMA type 4 were identified in a Brazilian cohort of 227 patients with SMA. The most common clinical symptom was limb‐girdle muscle weakness, observed in 15 patients (75%). The most frequent neurological findings were absent tendon reflexes in 18 (90%) and fasciculations in nine patients (45%). Sixteen patients (80%) had the homozygous deletion of exon 7 in the <jats:italic>SMN1</jats:italic> gene, with 12 patients (60%) showing four copies of the <jats:italic>SMN2</jats:italic> gene. The functional scales Hammersmith Functional Motor Scale Expanded, Amyotrophic Lateral Sclerosis Functional Rating Scale Revised, Revised Upper Limb Module and Spinal Muscular Atrophy Functional Rating Scale, as well as the six‐minute walk and the Time Up and Go tests showed a correlation with duration of disease. Motor Unit Number Index was correlated both with duration of disease and with performance in functional assessment. Radiological studies exhibited a typical pattern, with involvement of biceps femoris short head and gluteus minimus in all patients.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This study represents the largest cohort of patients with SMA type 4 and provides functional, genetic, radiological and neurophysiological features that can be used as potential biomarkers for the new specific genetic therapies for SMA.</jats:p></jats:sec>